BROAD SPECTRUM INFLUENZA VIRUS VACCINE

Information

  • Patent Application
  • 20230310576
  • Publication Number
    20230310576
  • Date Filed
    November 14, 2022
    a year ago
  • Date Published
    October 05, 2023
    8 months ago
Abstract
The disclosure relates to broad spectrum influenza virus ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines.
Description
BACKGROUND

Influenza viruses are members of the orthomyxoviridae family, and are classified into three distinct types (A, B, and C), based on antigenic differences between their nucleoprotein (NP) and matrix (M) protein. The orthomyxoviruses are enveloped animal viruses of approximately 100 nm in diameter. The influenza virions consist of an internal ribonucleoprotein core (a helical nucleocapsid) containing a single-stranded RNA genome, and an outer lipoprotein envelope lined inside by a matrix protein (M1). The segmented genome of influenza A virus consists of eight molecules (seven for influenza C virus) of linear, negative polarity, single-stranded RNAs, which encode several polypeptides including: the RNA-directed RNA polymerase proteins (PB2, PB1 and PA) and nucleoprotein (NP), which form the nucleocapsid; the matrix proteins (M1, M2, which is also a surface-exposed protein embedded in the virus membrane); two surface glycoproteins, which project from the lipoprotein envelope: hemagglutinin (HA) and neuraminidase (NA); and nonstructural proteins (NS1 and NS2). Transcription and replication of the genome takes place in the nucleus and assembly takes place at the plasma membrane.


Hemagglutinin is the major envelope glycoprotein of influenza A and B viruses, and hemagglutinin-esterase (HE) of influenza C viruses is a protein homologous to HA. The rapid evolution of the HA protein of the influenza virus results in the constant emergence of new strains, rendering the adaptive immune response of the host only partially protective to new infections. The biggest challenge for therapy and prophylaxis against influenza and other infections using traditional vaccines is the limitation of vaccines in breadth, providing protection only against closely related subtypes. In addition, the length of time required to complete current standard influenza virus vaccine production processes inhibits the rapid development and production of an adapted vaccine in a pandemic situation.


Deoxyribonucleic acid (DNA) vaccination is one technique used to stimulate humoral and cellular immune responses to foreign antigens, such as influenza antigens. The direct injection of genetically engineered DNA (e.g., naked plasmid DNA) into a living host results in a small number of its cells directly producing an antigen, resulting in a protective immunological response. With this technique, however, come potential problems, including the possibility of insertional mutagenesis, which could lead to the activation of oncogenes or the inhibition of tumor suppressor genes.


SUMMARY

Provided herein is a ribonucleic acid (RNA) vaccine (or a composition or an immunogenic composition) that builds on the knowledge that RNA (e.g., messenger RNA (mRNA)) can safely direct the body's cellular machinery to produce nearly any protein of interest, from native proteins to antibodies and other entirely novel protein constructs that can have therapeutic activity inside and outside of cells. The RNA vaccines of the present disclosure may be used to induce a balanced immune response against influenza virus, comprising both cellular and humoral immunity, without risking the possibility of insertional mutagenesis, for example.


The RNA (e.g., mRNA) vaccines may be utilized in various settings depending on the prevalence of the infection or the degree or level of unmet medical need. The RNA vaccines may be utilized to treat and/or prevent an influenza virus of various genotypes, strains, and isolates. The RNA vaccines typically have superior properties in that they produce much larger antibody titers and produce responses earlier than commercially available anti-viral therapeutic treatments. While not wishing to be bound by theory, it is believed that the RNA vaccines, as mRNA polynucleotides, are better designed to produce the appropriate protein conformation upon translation as the RNA vaccines co-opt natural cellular machinery. Unlike traditional vaccines, which are manufactured ex vivo and may trigger unwanted cellular responses, RNA (e.g., mRNA) vaccines are presented to the cellular system in a more native fashion.


There may be situations where persons are at risk for infection with more than one strain of influenza virus. RNA (e.g., mRNA) therapeutic vaccines are particularly amenable to combination vaccination approaches due to a number of factors including, but not limited to, speed of manufacture, ability to rapidly tailor vaccines to accommodate perceived geographical threat, and the like. Moreover, because the vaccines utilize the human body to produce the antigenic protein, the vaccines are amenable to the production of larger, more complex antigenic proteins, allowing for proper folding, surface expression, antigen presentation, etc. in the human subject. To protect against more than one strain of influenza, a combination vaccine can be administered that includes RNA (e.g., mRNA) encoding at least one antigenic polypeptide protein (or antigenic portion thereof) of a first influenza virus or organism and further includes RNA encoding at least one antigenic polypeptide protein (or antigenic portion thereof) of a second influenza virus or organism. RNA (e.g., mRNA) can be co-formulated, for example, in a single lipid nanoparticle (LNP) or can be formulated in separate LNPs for co-administration.


Some embodiments of the present disclosure provide influenza virus (influenza) vaccines (or compositions or immunogenic compositions) that include at least one RNA polynucleotide having an open reading frame encoding at least one influenza antigenic polypeptide.


In some embodiments, the at least one antigenic polypeptide is one of the defined antigenic subdomains of HA, termed HA1, HA2, or a combination of HA1 and HA2, and at least one antigenic polypeptide selected from neuraminidase (NA), nucleoprotein (NP), matrix protein 1 (M1), matrix protein 2 (M2), non-structural protein 1 (NS1) and non-structural protein 2 (NS2).


In some embodiments, the at least one antigenic polypeptide is HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2, and at least one antigenic polypeptide selected from NA, NP, M1, M2, NS1 and NS2.


In some embodiments, the at least one antigenic polypeptide is HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2 and at least two antigenic polypeptides selected from NA, NP, M1, M2, NS1 and NS2.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding an influenza virus protein.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding multiple influenza virus proteins.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (e.g., at least one HA1, HA2, or a combination of both).


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (e.g., at least one HA1, HA2, or a combination of both, of any one of or a combination of any or all of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, and/or H18) and at least one other RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a protein selected from a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein and a NS2 protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (e.g., at least one any one of or a combination of any or all of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, and/or H18) and at least two other RNAs (e.g., mRNAs) polynucleotides having two open reading frames encoding two proteins selected from a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein and a NS2 protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (e.g., at least one of any one of or a combination of any or all of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, and/or H18) and at least three other RNAs (e.g., mRNAs) polynucleotides having three open reading frames encoding three proteins selected from a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein and a NS2 protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (e.g., at least one of any one of or a combination of any or all of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, and/or H18) and at least four other RNAs (e.g., mRNAs) polynucleotides having four open reading frames encoding four proteins selected from a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein and a NS2 protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (e.g., at least one of any one of or a combination of any or all of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, and/or H18) and at least five other RNAs (e.g., mRNAs) polynucleotides having five open reading frames encoding five proteins selected from a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein and a NS2 protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (e.g., at least one of any one of or a combination of any or all of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, and/or H18), a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein and a NS2 protein obtained from influenza virus.


Some embodiments of the present disclosure provide the following novel influenza virus polypeptide sequences: H1HA10-Foldon_ANglyl; H1HA1OTM-PR8 (H1 A/Puerto Rico/8/34 HA); H1HA10-PR8-DS (H1 A/Puerto Rico/8/34 HA; pH1HA10-Cal04-DS (H1 A/California/04/2009 HA); Pandemic H1HA10 from California 04; pH1HA10-ferritin; HA10; Pandemic H1HA10 from California 04; Pandemic H1HA10 from California 04 strain/without foldon and with K68C/R76C mutation for trimerization; H1HA10 from A/Puerto Rico/8/34 strain, without foldon and with Y94D/N95L mutation for trimerization; H1HA10 from A/Puerto Rico/8/34 strain, without foldon and with K68C/R76C mutation for trimerization; HIN1 A/Viet Nam/850/2009; H3N2 A/Wisconsin/67/2005; H7N9 (A/Anhui/1/2013); H9N2 A/Hong Kong/1073/99; H10N8 A/JX346/2013.


Some embodiments of the present disclosure provide influenza virus (influenza) vaccines that include at least one RNA polynucleotide having an open reading frame encoding at least one influenza antigenic polypeptide. In some embodiments, an influenza vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding at least one influenza antigenic polypeptide comprising a modified sequence that is at least 75% (e.g., any number between 75% and 100%, inclusive, e.g., 70%, 80%, 85%, 90%, 95%, 99%, and 100%) identity to an amino acid sequence of the novel influenza virus sequences described above. The modified sequence can be at least 75% (e.g., any number between 75% and 100%, inclusive, e.g., 70%, 80%, 85%, 90%, 95%, 99%, and 100%) identical to an amino acid sequence of the novel influenza virus sequences described above.


Some embodiments of the present disclosure provide an isolated nucleic acid comprising a sequence encoding the novel influenza virus polypeptide sequences described above; an expression vector comprising the nucleic acid; and a host cell comprising the nucleic acid. The present disclosure also provides a method of producing a polypeptide of any of the novel influenza virus sequences described above. A method may include culturing the host cell in a medium under conditions permitting nucleic acid expression of the novel influenza virus sequences described above, and purifying from the cultured cell or the medium of the cell a novel influenza virus polypeptide. The present disclosure also provides antibody molecules, including full length antibodies and antibody derivatives, directed against the novel influenza virus sequences.


In some embodiments, an open reading frame of a RNA (e.g., mRNA) vaccine is codon-optimized. In some embodiments, at least one RNA polynucleotide encodes at least one antigenic polypeptide comprising an amino acid sequence identified by any one of SEQ ID NO: 1-444, 458, 460, 462-479, or 543-565 (see also Tables 7-13 and 26) and is codon optimized mRNA.


In some embodiments, a RNA (e.g., mRNA) vaccine further comprising an adjuvant.


Tables 7-13 provide National Center for Biotechnology Information (NCBI) accession numbers of interest. It should be understood that the phrase “an amino acid sequence of Tables 7-13” refers to an amino acid sequence identified by one or more NCBI accession numbers listed in 7-13. Each of the amino acid sequences, and variants having greater than 95% identity or greater than 98% identity to each of the amino acid sequences encompassed by the accession numbers of Tables 7-13 are included within the constructs (polynucleotides/polypeptides) of the present disclosure.


In some embodiments, at least one mRNA polynucleotide is encoded by a nucleic acid comprising a sequence identified by any one of SEQ ID NO: 447-457, 459, 461, 505-523, or 570-573 and having less than 80% identity to wild-type mRNA sequence. In some embodiments, at least one mRNA polynucleotide is encoded by a nucleic acid comprising a sequence identified by any one SEQ ID NO: 447-457, 459, 461, 505-523, or 570-573 and having less than 75%, 85% or 95% identity to a wild-type mRNA sequence. In some embodiments, at least one mRNA polynucleotide is encoded by nucleic acid comprising a sequence identified by any one of SEQ ID NO: 447-457, 459, 461, 505-523, or 570-573 and having less than 50-80%, 60-80%, 40-80%, 30-80%, 70-80%, 75-80% or 78-80% identity to wild-type mRNA sequence. In some embodiments, at least one mRNA polynucleotide is encoded by a nucleic acid comprising a sequence identified by any one of SEQ ID NO: 447-457, 459, 461, 505-523, or 570-573 and having less than 40-85%, 50-85%, 60-85%, 30-85%, 70-85%, 75-85% or 80-85% identity to wild-type mRNA sequence. In some embodiments, at least one mRNA polynucleotide is encoded by a nucleic acid comprising a sequence identified by any one of SEQ ID NO: 447-457, 459, 461, 505-523, or 570-573 and having less than 40-90%, 50-90%, 60-90%, 30-90%, 70-90%, 75-90%, 80-90%, or 85-90% identity to wild-type mRNA sequence.


In some embodiments, at least one mRNA polynucleotide comprises a sequence identified by any one of SEQ ID NO: 491-503 or 566-569 and has less than 80% identity to wild-type mRNA sequence. In some embodiments, at least one mRNA polynucleotide is encoded by a nucleic acid comprising a sequence identified by any one SEQ ID NO: 491-503 or 566-569 and has less than 75%, 85% or 95% identity to a wild-type mRNA sequence. In some embodiments, at least one mRNA polynucleotide is encoded by nucleic acid comprising a sequence identified by any one of SEQ ID NO: 491-503 or 566-569 and has less than 50-80%, 60-80%, 40-80%, 30-80%, 70-80%, 75-80% or 78-80% identity to wild-type mRNA sequence. In some embodiments, at least one mRNA polynucleotide is encoded by a nucleic acid comprising a sequence identified by any one of SEQ ID NO: 491-503 or 566-569 and has less than 40-85%, 50-85%, 60-85%, 30-85%, 70-85%, 75-85% or 80-85% identity to wild-type mRNA sequence. In some embodiments, at least one mRNA polynucleotide is encoded by a nucleic acid comprising a sequence identified by any one of SEQ ID NO: 491-503 or 566-569 and has less than 40-90%, 50-90%, 60-90%, 30-90%, 70-90%, 75-90%, 80-90%, or 85-90% identity to wild-type mRNA sequence.


In some embodiments, at least one RNA polynucleotide encodes at least one antigenic polypeptide comprising an amino acid sequence identified by any one of SEQ ID NO: 1-444, 458, 460, 462-479, or 543-565 (see also Tables 7-13 and 26) and having at least 80% (e.g., 85%, 90%, 95%, 98%, 99%) identity to wild-type mRNA sequence, but does not include wild-type mRNA sequence.


In some embodiments, at least one RNA polynucleotide encodes at least one antigenic polypeptide comprising an amino acid sequence identified by any one of SEQ ID NO: 1-444, 458, 460, 462-479, or 543-565 (see also Tables 7-13 and 26) and has less than 95%, 90%, 85%, 80% or 75% identity to wild-type mRNA sequence. In some embodiments, at least one RNA polynucleotide encodes at least one antigenic polypeptide comprising an amino acid sequence identified by any one of SEQ ID NO: 1-444, 458, 460, 462-479, or 543-565 (see also Tables 7-13 and 26) and has 30-80%, 40-80%, 50-80%, 60-80%, 70-80%, 75-80% or 78-80%, 30-85%, 40-85%, 50-805%, 60-85%, 70-85%, 75-85% or 78-85%, 30-90%, 40-90%, 50-90%, 60-90%, 70-90%, 75-90%, 80-90% or 85-90% identity to wild-type mRNA sequence.


In some embodiments, at least one RNA polynucleotide encodes at least one antigenic polypeptide having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to an amino acid sequence identified by any one of SEQ ID NO: 1-444, 458, 460, 462-479, or 543-565 (see also Tables 7-13 and 26). In some embodiments, at least one RNA polynucleotide encodes at least one antigenic polypeptide having 95%-99% identity to an amino acid sequence identified by any one of 1-444, 458, 460, 462-479, or 543-565 (see also Tables 7-13 and 26).


In some embodiments, at least one RNA polynucleotide encodes at least one antigenic polypeptide having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to amino acid sequence identified by any one of SEQ ID NO: 1-444, 458, 460, 462-479, or 543-565 (see also Tables 7-13 and 26) and having membrane fusion activity. In some embodiments, at least one RNA polynucleotide encodes at least one antigenic polypeptide having 95%-99% identity to amino acid sequence identified by any one of SEQ ID NO: 1-444, 458, 460, 462-479, or 543-565 (see also Tables 7-13 and 26) and having membrane fusion activity.


In some embodiments, at least one RNA polynucleotide encodes at least one influenza antigenic polypeptide that attaches to cell receptors.


In some embodiments, at least one RNA polynucleotide encodes at least one influenza antigenic polypeptide that causes fusion of viral and cellular membranes.


In some embodiments, at least one RNA polynucleotide encodes at least one influenza antigenic polypeptide that is responsible for binding of the virus to a cell being infected.


Some embodiments of the present disclosure provide a vaccine that includes at least one ribonucleic acid (RNA) (e.g., mRNA) polynucleotide having an open reading frame encoding at least one influenza antigenic polypeptide, at least one 5′ terminal cap and at least one chemical modification, formulated within a lipid nanoparticle.


In some embodiments, a 5′ terminal cap is 7mG(5′)ppp(5′)NlmpNp.


In some embodiments, at least one chemical modification is selected from pseudouridine, N1-methylpseudouridine, N1-ethylpseudouridine, 2-thiouridine, 4′-thiouridine, 5-methylcytosine, 5-methyluridine, 2-thio-1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine, 2-thio-dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine, 4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine, 4-thio-pseudouridine, 5-aza-uridine, dihydropseudouridine, 5-methoxyuridine and 2′-O-methyl uridine. In some embodiments, the chemical modification is in the 5-position of the uracil. In some embodiments, the chemical modification is a N1-methylpseudouridine. In some embodiments, the chemical modification is a N1-ethylpseudouridine.


In some embodiments, a lipid nanoparticle comprises a cationic lipid, a PEG-modified lipid, a sterol and a non-cationic lipid. In some embodiments, a cationic lipid is an ionizable cationic lipid and the non-cationic lipid is a neutral lipid, and the sterol is a cholesterol. In some embodiments, a cationic lipid is selected from the group consisting of 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, (12Z,15Z)-N,N-dimethyl-2-nonylhenicosa-12,15-dien-1-amine, and N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]heptadecan-8-amine.


In some embodiments, the cationic lipid is




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In some embodiments, the cationic lipid is




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In some embodiments, at least one cationic lipid selected from compounds of Formula (I):




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    • or a salt or isomer thereof, wherein:

    • R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′R’;

    • R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;

    • R4 is selected from the group consisting of a C3-6 carbocycle, —(CH2)nQ, —(CH2)nCHQR, —CHQR, —CQ(R)2, and unsubstituted C1-6 alkyl, where Q is selected from a carbocycle, heterocycle, —OR, —O(CH2)nN(R)2, —C(O)OR, —OC(O)R, —CX3, —CX2H, —CXH2, —CN, —N(R)2, —C(O)N(R)2, —N(R)C(O)R, —N(R)S(O)2R, —N(R)C(O)N(R)2, —N(R)C(S)N(R)2, —N(R)R8, —O(CH2)nOR, —N(R)C(═NR9)N(R)2, —N(R)C(═CHR9)N(R)2, —OC(O)N(R)2, —N(R)C(O)OR, —N(OR)C(O)R, —N(OR)S(O)2R, —N(OR)C(O)OR, —N(OR)C(O)N(R)2, —N(OR)C(S)N(R)2, —N(OR)C(═NR9)N(R)2, —N(OR)C(═CHR9)N(R)2, —C(═NR9)N(R)2, —C(═NR9)R, —C(O)N(R)OR, and —C(R)N(R)2C(O)OR, and each n is independently selected from 1, 2, 3, 4, and 5;

    • each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′)C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O)(OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;

    • R7 is selected from the group consisting of C13 alkyl, C2-3 alkenyl, and H;

    • R8 is selected from the group consisting of C3-6 carbocycle and heterocycle;

    • R9 is selected from the group consisting of H, CN, NO2, C1-6 alkyl, —OR, —S(O)2R, —S(O)2N(R)2, C2-6 alkenyl, C3-6 carbocycle and heterocycle;

    • each R is independently selected from the group consisting of C13 alkyl, C2-3 alkenyl, and H;

    • each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;

    • each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;

    • each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;

    • each Y is independently a C3-6 carbocycle;

    • each X is independently selected from the group consisting of F, Cl, Br, and I; and m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.





In some embodiments, a subset of compounds of Formula (I) includes those in which when R4 is —(CH2)nQ, —(CH2)nCHQR, —CHQR, or —CQ(R)2, then (i) Q is not —N(R)2 when n is 1, 2, 3, 4 or 5, or (ii) Q is not 5, 6, or 7-membered heterocycloalkyl when n is 1 or 2.


In some embodiments, a subset of compounds of Formula (I) includes those in which R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′R’;

    • R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;
    • R4 is selected from the group consisting of a C3-6 carbocycle, —(CH2)nQ, —(CH2)nCHQR, —CHQR, —CQ(R)2, and unsubstituted C1-6 alkyl, where Q is selected from a C3-6 carbocycle, a 5- to 14-membered heteroaryl having one or more heteroatoms selected from N, O, and S, —OR, —O(CH2)nN(R)2, —C(O)OR, —OC(O)R, —CX3, —CX2H, —CXH2, —CN, —C(O)N(R)2, —N(R)C(O)R, —N(R)S(O)2R, —N(R)C(O)N(R)2, —N(R)C(S)N(R)2, —CRN(R)2C(O)OR, —N(R)R8, —O(CH2)nOR, —N(R)C(═NR9)N(R)2, —N(R)C(═CHR9)N(R)2, —OC(O)N(R)2, —N(R)C(O)OR, —N(OR)C(O)R, —N(OR)S(O)2R, —N(OR)C(O)OR, —N(OR)C(O)N(R)2, —N(OR)C(S)N(R)2, —N(OR)C(═NR9)N(R)2, —N(OR)C(═CHR9)N(R)2, —C(═NR9)N(R)2, —C(═NR9)R, —C(O)N(R)OR, and a 5- to 14-membered heterocycloalkyl having one or more heteroatoms selected from N, O, and S which is substituted with one or more substituents selected from oxo (═O), OH, amino, mono- or di-alkylamino, and C1-3 alkyl, and each n is independently selected from 1, 2, 3, 4, and 5;
    • each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′)C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O)(OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;
    • R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • R8 is selected from the group consisting of C3-6 carbocycle and heterocycle;
    • R9 is selected from the group consisting of H, CN, NO2, C1-6 alkyl, —OR, —S(O)2R, —S(O)2N(R)2, C2-6 alkenyl, C3-6 carbocycle and heterocycle;
    • each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;
    • each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;
    • each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;
    • each Y is independently a C3-6 carbocycle;
    • each X is independently selected from the group consisting of F, Cl, Br, and I; and
    • m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
    • or salts or isomers thereof.


In some embodiments, a subset of compounds of Formula (I) includes those in which R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′R’;

    • R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;
    • R4 is selected from the group consisting of a C3-6 carbocycle, —(CH2)nQ, —(CH2)nCHQR, —CHQR,-CQ(R)2, and unsubstituted C1-6 alkyl, where Q is selected from a C3-6 carbocycle, a 5- to 14-membered heterocycle having one or more heteroatoms selected from N, O, and S, —OR, —O(CH2)nN(R)2, —C(O)OR, —OC(O)R, —CX3, —CX2H, —CXH2, —CN, —C(O)N(R)2, —N(R)C(O)R, —N(R)S(O)2R, —N(R)C(O)N(R)2, —N(R)C(S)N(R)2, —CRN(R)2C(O)OR, —N(R)R8, —O(CH2)nOR, —N(R)C(═NR9)N(R)2, —N(R)C(═CHR9)N(R)2, —OC(O)N(R)2, —N(R)C(O)OR, —N(OR)C(O)R, —N(OR)S(O)2R, —N(OR)C(O)OR, —N(OR)C(O)N(R)2, —N(OR)C(S)N(R)2, —N(OR)C(═NR9)N(R)2, —N(OR)C(═CHR9)N(R)2, —C(═NR9)R, —C(O)N(R)OR, and —C(═NR9)N(R)2, and each n is independently selected from 1, 2, 3, 4, and 5; and when Q is a 5- to 14-membered heterocycle and (i) R4 is —(CH2)nQ in which n is 1 or 2, or (ii) R4 is —(CH2)nCHQR in which n is 1, or (iii) R4 is-CHQR, and -CQ(R)2, then Q is either a 5- to 14-membered heteroaryl or 8- to 14-membered heterocycloalkyl;
    • each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H; M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′)C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O)(OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;
    • R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • R8 is selected from the group consisting of C3-6 carbocycle and heterocycle;
    • R9 is selected from the group consisting of H, CN, NO2, C1-6 alkyl, —OR, —S(O)2R, —S(O)2N(R)2, C2-6 alkenyl, C3-6 carbocycle and heterocycle;
    • each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;
    • each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;
    • each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;
    • each Y is independently a C3-6 carbocycle;
    • each X is independently selected from the group consisting of F, Cl, Br, and I; and m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13, or salts or isomers thereof.


In some embodiments, a subset of compounds of Formula (I) includes those in which R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′R’;

    • R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;
    • R4 is selected from the group consisting of a C3-6 carbocycle, —(CH2)nQ, —(CH2)nCHQR, —CHQR,-CQ(R)2, and unsubstituted C1-6 alkyl, where Q is selected from a C3-6 carbocycle, a 5- to 14-membered heteroaryl having one or more heteroatoms selected from N, O, and S, —OR, —O(CH2)nN(R)2, —C(O)OR, —OC(O)R, —CX3, —CX2H, —CXH2, —CN, —C(O)N(R)2, —N(R)C(O)R, —N(R)S(O)2R, —N(R)C(O)N(R)2, —N(R)C(S)N(R)2, —CRN(R)2C(O)OR, —N(R)R8, —O(CH2)nOR, —N(R)C(═NR9)N(R)2, —N(R)C(═CHR9)N(R)2, —OC(O)N(R)2, —N(R)C(O)OR, —N(OR)C(O)R, —N(OR)S(O)2R, —N(OR)C(O)OR, —N(OR)C(O)N(R)2, —N(OR)C(S)N(R)2, —N(OR)C(═NR9)N(R)2, —N(OR)C(═CHR9)N(R)2, —C(═NR9)R, —C(O)N(R)OR, and —C(═NR9)N(R)2, and each n is independently selected from 1, 2, 3, 4, and 5; each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H; each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H; M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′)C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O)(OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;
    • R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • R8 is selected from the group consisting of C3-6 carbocycle and heterocycle;
    • R9 is selected from the group consisting of H, CN, NO2, C1-6 alkyl, —OR, —S(O)2R, —S(O)2N(R)2, C2-6 alkenyl, C3-6 carbocycle and heterocycle;
    • each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;
    • each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;
    • each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;
    • each Y is independently a C3-6 carbocycle;
    • each X is independently selected from the group consisting of F, Cl, Br, and I; and m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
    • or salts or isomers thereof.


In some embodiments, a subset of compounds of Formula (I) includes those in which R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′ R’;

    • R2 and R3 are independently selected from the group consisting of H, C2-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;
    • R4 is —(CH2)nQ or —(CH2)·CHQR, where Q is —N(R)2, and n is selected from 3, 4, and 5;
    • each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′)C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O)(OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;
    • R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;
    • each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;
    • each R* is independently selected from the group consisting of C1-12 alkyl and C1-12 alkenyl;
    • each Y is independently a C3-6 carbocycle;
    • each X is independently selected from the group consisting of F, Cl, Br, and I; and m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13, or salts or isomers thereof.


In some embodiments, a subset of compounds of Formula (I) includes those in which R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′R’;

    • R2 and R3 are independently selected from the group consisting of C1-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;
    • R4 is selected from the group consisting of —(CH2)nQ, —(CH2)nCHQR, —CHQR, and -CQ(R)2,
    • where Q is —N(R)2, and n is selected from 1, 2, 3, 4, and 5;
    • each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′)C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O)(OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;
    • R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;
    • each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;
    • each R* is independently selected from the group consisting of C1-12 alkyl and C1-12 alkenyl;
    • each Y is independently a C3-6 carbocycle;
    • each X is independently selected from the group consisting of F, Cl, Br, and I; and
    • m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
    • or salts or isomers thereof.


In some embodiments, a subset of compounds of Formula (I) includes those of Formula (IA):




embedded image


or a salt or isomer thereof, wherein 1 is selected from 1, 2, 3, 4, and 5; m is selected from 5, 6, 7, 8, and 9; M1 is a bond or M′; R4 is unsubstituted C1-3 alkyl, or —(CH2)nQ, in which Q is OH, —NHC(S)N(R)2, —NHC(O)N(R)2, —N(R)C(O)R, —N(R)S(O)2R, —N(R)R8, —NHC(═NR9)N(R)2, —NHC(═CHR9)N(R)2, —OC(O)N(R)2, —N(R)C(O)OR, heteroaryl or heterocycloalkyl; M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —P(O)(OR′)O—, —S—S—, an aryl group, and a heteroaryl group; and R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, and C2-14 alkenyl.


Some embodiments of the present disclosure provide a vaccine that includes at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding at least one influenza antigenic polypeptide, wherein at least 80% (e.g., 85%, 90%, 95%, 98%, 99%) of the uracil in the open reading frame have a chemical modification, optionally wherein the vaccine is formulated in a lipid nanoparticle (e.g., a lipid nanoparticle comprises a cationic lipid, a PEG-modified lipid, a sterol and a non-cationic lipid).


In some embodiments, 100% of the uracil in the open reading frame have a chemical modification. In some embodiments, a chemical modification is in the 5-position of the uracil. In some embodiments, a chemical modification is a N1-methyl pseudouridine. In some embodiments, 100% of the uracil in the open reading frame have a N1-methyl pseudouridine in the 5-position of the uracil.


In some embodiments, an open reading frame of a RNA (e.g., mRNA) polynucleotide encodes at least two influenza antigenic polypeptides. In some embodiments, the open reading frame encodes at least five or at least ten antigenic polypeptides. In some embodiments, the open reading frame encodes at least 100 antigenic polypeptides. In some embodiments, the open reading frame encodes 2-100 antigenic polypeptides.


In some embodiments, a vaccine comprises at least two RNA (e.g., mRNA) polynucleotides, each having an open reading frame encoding at least one influenza antigenic polypeptide. In some embodiments, the vaccine comprises at least five or at least ten RNA (e.g., mRNA) polynucleotides, each having an open reading frame encoding at least one antigenic polypeptide. In some embodiments, the vaccine comprises at least 100 RNA (e.g., mRNA) polynucleotides, each having an open reading frame encoding at least one antigenic polypeptide. In some embodiments, the vaccine comprises 2-100 RNA (e.g., mRNA) polynucleotides, each having an open reading frame encoding at least one antigenic polypeptide.


In some embodiments, at least one influenza antigenic polypeptide is fused to a signal peptide. In some embodiments, the signal peptide is selected from: a HuIgGk signal peptide (METPAQLLFLLLLWLPDTTG; SEQ ID NO: 480); IgE heavy chain epsilon-1 signal peptide (MDWTWILFLVAAATRVHS; SEQ ID NO: 481); Japanese encephalitis PRM signal sequence (MLGSNSGQRVVFTILLLLVAPAYS; SEQ ID NO: 482), VSVg protein signal sequence (MKCLLYLAFLFIGVNCA; SEQ ID NO: 483) and Japanese encephalitis JEV signal sequence (MWLVSLAIVTACAGA; SEQ ID NO: 484).


In some embodiments, the signal peptide is fused to the N-terminus of at least one antigenic polypeptide. In some embodiments, a signal peptide is fused to the C-terminus of at least one antigenic polypeptide.


In some embodiments, at least one influenza antigenic polypeptide comprises a mutated N-linked glycosylation site.


Also provided herein is an influenza RNA (e.g., mRNA) vaccine of any one of the foregoing paragraphs formulated in a nanoparticle (e.g., a lipid nanoparticle).


In some embodiments, the nanoparticle has a mean diameter of 50-200 nm. In some embodiments, the nanoparticle is a lipid nanoparticle. In some embodiments, the lipid nanoparticle comprises a cationic lipid, a PEG-modified lipid, a sterol and a non-cationic lipid. In some embodiments, the lipid nanoparticle comprises a molar ratio of about 20-60% cationic lipid, 0.5-15% PEG-modified lipid, 25-55% sterol, and 25% non-cationic lipid. In some embodiments, the cationic lipid is an ionizable cationic lipid and the non-cationic lipid is a neutral lipid, and the sterol is a cholesterol. In some embodiments, the cationic lipid is selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate.


In some embodiments, the nanoparticle has a polydispersity value of less than 0.4 (e.g., less than 0.3, 0.2 or 0.1).


In some embodiments, the nanoparticle has a net neutral charge at a neutral pH value.


In some embodiments, the RNA (e.g., mRNA) vaccine is multivalent.


Some embodiments of the present disclosure provide methods of inducing an antigen specific immune response in a subject, comprising administering to the subject any of the RNA (e.g., mRNA) vaccine as provided herein in an amount effective to produce an antigen-specific immune response. In some embodiments, the RNA (e.g., mRNA) vaccine is an influenza vaccine. In some embodiments, the RNA (e.g., mRNA) vaccine is a combination vaccine comprising a combination of influenza vaccines (a broad spectrum influenza vaccine).


In some embodiments, an antigen-specific immune response comprises a T cell response or a B cell response.


In some embodiments, a method of producing an antigen-specific immune response comprises administering to a subject a single dose (no booster dose) of an influenza RNA (e.g., mRNA) vaccine of the present disclosure.


In some embodiments, a method further comprises administering to the subject a second (booster) dose of an influenza RNA (e.g., mRNA) vaccine. Additional doses of an influenza RNA (e.g., mRNA) vaccine may be administered.


In some embodiments, the subjects exhibit a seroconversion rate of at least 80% (e.g., at least 85%, at least 90%, or at least 95%) following the first dose or the second (booster) dose of the vaccine. Seroconversion is the time period during which a specific antibody develops and becomes detectable in the blood. After seroconversion has occurred, a virus can be detected in blood tests for the antibody. During an infection or immunization, antigens enter the blood, and the immune system begins to produce antibodies in response. Before seroconversion, the antigen itself may or may not be detectable, but antibodies are considered absent. During seroconversion, antibodies are present but not yet detectable. Any time after seroconversion, the antibodies can be detected in the blood, indicating a prior or current infection.


In some embodiments, an influenza RNA (e.g., mRNA) vaccine is administered to a subject by intradermal injection, intramuscular injection, or by intranasal administration. In some embodiments, an influenza RNA (e.g., mRNA) vaccine is administered to a subject by intramuscular injection.


Some embodiments, of the present disclosure provide methods of inducing an antigen specific immune response in a subject, including administering to a subject an influenza RNA (e.g., mRNA) vaccine in an effective amount to produce an antigen specific immune response in a subject. Antigen-specific immune responses in a subject may be determined, in some embodiments, by assaying for antibody titer (for titer of an antibody that binds to an influenza antigenic polypeptide) following administration to the subject of any of the influenza RNA (e.g., mRNA) vaccines of the present disclosure. In some embodiments, the anti-antigenic polypeptide antibody titer produced in the subject is increased by at least 1 log relative to a control. In some embodiments, the anti-antigenic polypeptide antibody titer produced in the subject is increased by 1-3 log relative to a control.


In some embodiments, the anti-antigenic polypeptide antibody titer produced in a subject is increased at least 2 times relative to a control. In some embodiments, the anti-antigenic polypeptide antibody titer produced in the subject is increased at least 5 times relative to a control. In some embodiments, the anti-antigenic polypeptide antibody titer produced in the subject is increased at least 10 times relative to a control. In some embodiments, the anti-antigenic polypeptide antibody titer produced in the subject is increased 2-10 times relative to a control.


In some embodiments, the control is an anti-antigenic polypeptide antibody titer produced in a subject who has not been administered a RNA (e.g., mRNA) vaccine of the present disclosure. In some embodiments, the control is an anti-antigenic polypeptide antibody titer produced in a subject who has been administered a live attenuated or inactivated influenza, or wherein the control is an anti-antigenic polypeptide antibody titer produced in a subject who has been administered a recombinant or purified influenza protein vaccine. In some embodiments, the control is an anti-antigenic polypeptide antibody titer produced in a subject who has been administered an influenza virus-like particle (VLP) vaccine (see, e.g., Cox R G et al., J Virol. 2014 June; 88(11): 6368-6379).


A RNA (e.g., mRNA) vaccine of the present disclosure is administered to a subject in an effective amount (an amount effective to induce an immune response). In some embodiments, the effective amount is a dose equivalent to an at least 2-fold, at least 4-fold, at least 10-fold, at least 100-fold, at least 1000-fold reduction in the standard of care dose of a recombinant influenza protein vaccine, wherein the anti-antigenic polypeptide antibody titer produced in the subject is equivalent to an anti-antigenic polypeptide antibody titer produced in a control subject administered the standard of care dose of a recombinant influenza protein vaccine, a purified influenza protein vaccine, a live attenuated influenza vaccine, an inactivated influenza vaccine, or an influenza VLP vaccine. In some embodiments, the effective amount is a dose equivalent to 2-1000-fold reduction in the standard of care dose of a recombinant influenza protein vaccine, wherein the anti-antigenic polypeptide antibody titer produced in the subject is equivalent to an anti-antigenic polypeptide antibody titer produced in a control subject administered the standard of care dose of a recombinant influenza protein vaccine, a purified influenza protein vaccine, a live attenuated influenza vaccine, an inactivated influenza vaccine, or an influenza VLP vaccine.


In some embodiments, the control is an anti-antigenic polypeptide antibody titer produced in a subject who has been administered a virus-like particle (VLP) vaccine comprising structural proteins of influenza.


In some embodiments, the RNA (e.g., mRNA) vaccine is formulated in an effective amount to produce an antigen specific immune response in a subject.


In some embodiments, the effective amount is a total dose of 25 μg to 1000 μg, or 50 μg to 1000 μg. In some embodiments, the effective amount is a total dose of 100 μg. In some embodiments, the effective amount is a dose of 25 μg administered to the subject a total of two times. In some embodiments, the effective amount is a dose of 100 μg administered to the subject a total of two times. In some embodiments, the effective amount is a dose of 400 μg administered to the subject a total of two times. In some embodiments, the effective amount is a dose of 500 μg administered to the subject a total of two times.


In some embodiments, the efficacy (or effectiveness) of a RNA (e.g., mRNA) vaccine is greater than 60%. In some embodiments, the RNA (e.g., mRNA) polynucleotide of the vaccine at least one Influenza antigenic polypeptide.


Vaccine efficacy may be assessed using standard analyses (see, e.g., Weinberg et al., J Infect Dis. 2010 Jun. 1; 201(11):1607-10). For example, vaccine efficacy may be measured by double-blind, randomized, clinical controlled trials. Vaccine efficacy may be expressed as a proportionate reduction in disease attack rate (AR) between the unvaccinated (ARU) and vaccinated (ARV) study cohorts and can be calculated from the relative risk (RR) of disease among the vaccinated group with use of the following formulas:





Efficacy=(ARU−ARV)/ARU×100; and





Efficacy=(1−RR)×100.


Likewise, vaccine effectiveness may be assessed using standard analyses (see, e.g., Weinberg et al., J Infect Dis. 2010 Jun. 1; 201(11):1607-10). Vaccine effectiveness is an assessment of how a vaccine (which may have already proven to have high vaccine efficacy) reduces disease in a population. This measure can assess the net balance of benefits and adverse effects of a vaccination program, not just the vaccine itself, under natural field conditions rather than in a controlled clinical trial. Vaccine effectiveness is proportional to vaccine efficacy (potency) but is also affected by how well target groups in the population are immunized, as well as by other non-vaccine-related factors that influence the ‘real-world’ outcomes of hospitalizations, ambulatory visits, or costs. For example, a retrospective case control analysis may be used, in which the rates of vaccination among a set of infected cases and appropriate controls are compared. Vaccine effectiveness may be expressed as a rate difference, with use of the odds ratio (OR) for developing infection despite vaccination:





Effectiveness=(1−OR)×100.


In some embodiments, the efficacy (or effectiveness) of a RNA (e.g., mRNA) vaccine is at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, or at least 90%.


In some embodiments, the vaccine immunizes the subject against Influenza for up to 2 years. In some embodiments, the vaccine immunizes the subject against Influenza for more than 2 years, more than 3 years, more than 4 years, or for 5-10 years.


In some embodiments, the subject is about 5 years old or younger. For example, the subject may be between the ages of about 1 year and about 5 years (e.g., about 1, 2, 3, 5 or 5 years), or between the ages of about 6 months and about 1 year (e.g., about 6, 7, 8, 9, 10, 11 or 12 months). In some embodiments, the subject is about 12 months or younger (e.g., 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 months or 1 month). In some embodiments, the subject is about 6 months or younger.


In some embodiments, the subject was born full term (e.g., about 37-42 weeks). In some embodiments, the subject was born prematurely, for example, at about 36 weeks of gestation or earlier (e.g., about 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26 or 25 weeks). For example, the subject may have been born at about 32 weeks of gestation or earlier. In some embodiments, the subject was born prematurely between about 32 weeks and about 36 weeks of gestation. In such subjects, a RNA (e.g., mRNA) vaccine may be administered later in life, for example, at the age of about 6 months to about 5 years, or older.


In some embodiments, the subject is a young adult between the ages of about 20 years and about 50 years (e.g., about 20, 25, 30, 35, 40, 45 or 50 years old).


In some embodiments, the subject is an elderly subject about 60 years old, about 70 years old, or older (e.g., about 60, 65, 70, 75, 80, 85 or 90 years old).


In some embodiments, the subject has been exposed to influenza (e.g., C. trachomatis); the subject is infected with influenza (e.g., C. trachomatis); or subject is at risk of infection by influenza (e.g., C. trachomatis).


In some embodiments, the subject is immunocompromised (has an impaired immune system, e.g., has an immune disorder or autoimmune disorder).


In some embodiments the nucleic acid vaccines described herein are chemically modified. In other embodiments the nucleic acid vaccines are unmodified.


Yet other aspects provide compositions for and methods of vaccinating a subject comprising administering to the subject a nucleic acid vaccine comprising one or more RNA polynucleotides having an open reading frame encoding a first virus antigenic polypeptide, wherein the RNA polynucleotide does not include a stabilization element, and wherein an adjuvant is not coformulated or co-administered with the vaccine.


In other aspects the invention is a composition for or method of vaccinating a subject comprising administering to the subject a nucleic acid vaccine comprising one or more RNA polynucleotides having an open reading frame encoding a first antigenic polypeptide wherein a dosage of between 10 μg/kg and 400 μg/kg of the nucleic acid vaccine is administered to the subject. In some embodiments the dosage of the RNA polynucleotide is 1-5 μg, 5-10 μg, 10-15 μg, 15-20 μg, 10-25 μg, 20-25 μg, 20-50 μg, 30-50 μg, 40-50 μg, 40-60 μg, 60-80 μg, 60-100 μg, 50-100 μg, 80-120 μg, 40-120 μg, 40-150 μg, 50-150 μg, 50-200 μg, 80-200 μg, 100-200 μg, 120-250 μg, 150-250 μg, 180-280 μg, 200-300 μg, 50-300 μg, 80-300 μg, 100-300 μg, 40-300 μg, 50-350 μg, 100-350 μg, 200-350 μg, 300-350 μg, 320-400 μg, 40-380 μg, 40-100 μg, 100-400 μg, 200-400 μg, or 300-400 μg per dose. In some embodiments, the nucleic acid vaccine is administered to the subject by intradermal or intramuscular injection. In some embodiments, the nucleic acid vaccine is administered to the subject on day zero. In some embodiments, a second dose of the nucleic acid vaccine is administered to the subject on day twenty one.


In some embodiments, a dosage of 25 micrograms of the RNA polynucleotide is included in the nucleic acid vaccine administered to the subject. In some embodiments, a dosage of 100 micrograms of the RNA polynucleotide is included in the nucleic acid vaccine administered to the subject. In some embodiments, a dosage of 50 micrograms of the RNA polynucleotide is included in the nucleic acid vaccine administered to the subject. In some embodiments, a dosage of 75 micrograms of the RNA polynucleotide is included in the nucleic acid vaccine administered to the subject. In some embodiments, a dosage of 150 micrograms of the RNA polynucleotide is included in the nucleic acid vaccine administered to the subject. In some embodiments, a dosage of 400 micrograms of the RNA polynucleotide is included in the nucleic acid vaccine administered to the subject. In some embodiments, a dosage of 200 micrograms of the RNA polynucleotide is included in the nucleic acid vaccine administered to the subject. In some embodiments, the RNA polynucleotide accumulates at a 100 fold higher level in the local lymph node in comparison with the distal lymph node. In other embodiments the nucleic acid vaccine is chemically modified and in other embodiments the nucleic acid vaccine is not chemically modified.


Aspects of the invention provide a nucleic acid vaccine comprising one or more RNA polynucleotides having an open reading frame encoding a first antigenic polypeptide, wherein the RNA polynucleotide does not include a stabilization element, and a pharmaceutically acceptable carrier or excipient, wherein an adjuvant is not included in the vaccine. In some embodiments, the stabilization element is a histone stem-loop. In some embodiments, the stabilization element is a nucleic acid sequence having increased GC content relative to wild type sequence.


Aspects of the invention provide nucleic acid vaccines comprising one or more RNA polynucleotides having an open reading frame encoding a first antigenic polypeptide, wherein the RNA polynucleotide is present in the formulation for in vivo administration to a host, which confers an antibody titer superior to the criterion for seroprotection for the first antigen for an acceptable percentage of human subjects. In some embodiments, the antibody titer produced by the mRNA vaccines of the invention is a neutralizing antibody titer. In some embodiments the neutralizing antibody titer is greater than a protein vaccine. In other embodiments the neutralizing antibody titer produced by the mRNA vaccines of the invention is greater than an adjuvanted protein vaccine. In yet other embodiments the neutralizing antibody titer produced by the mRNA vaccines of the invention is 1,000-10,000, 1,200-10,000, 1,400-10,000, 1,500-10,000, 1,000-5,000, 1,000-4,000, 1,800-10,000, 2000-10,000, 2,000-5,000, 2,000-3,000, 2,000-4,000, 3,000-5,000, 3,000-4,000, or 2,000-2,500. A neutralization titer is typically expressed as the highest serum dilution required to achieve a 50% reduction in the number of plaques.


Also provided are nucleic acid vaccines comprising one or more RNA polynucleotides having an open reading frame encoding a first antigenic polypeptide, wherein the RNA polynucleotide is present in a formulation for in vivo administration to a host for eliciting a longer lasting high antibody titer than an antibody titer elicited by an mRNA vaccine having a stabilizing element or formulated with an adjuvant and encoding the first antigenic polypeptide. In some embodiments, the RNA polynucleotide is formulated to produce a neutralizing antibodies within one week of a single administration. In some embodiments, the adjuvant is selected from a cationic peptide and an immunostimulatory nucleic acid. In some embodiments, the cationic peptide is protamine.


Aspects provide nucleic acid vaccines comprising one or more RNA polynucleotides having an open reading frame comprising at least one chemical modification or optionally no modified nucleotides, the open reading frame encoding a first antigenic polypeptide, wherein the RNA polynucleotide is present in the formulation for in vivo administration to a host such that the level of antigen expression in the host significantly exceeds a level of antigen expression produced by an mRNA vaccine having a stabilizing element or formulated with an adjuvant and encoding the first antigenic polypeptide.


Other aspects provide nucleic acid vaccines comprising one or more RNA polynucleotides having an open reading frame comprising at least one chemical modification or optionally no modified nucleotides, the open reading frame encoding a first antigenic polypeptide, wherein the vaccine has at least 10 fold less RNA polynucleotide than is required for an unmodified mRNA vaccine to produce an equivalent antibody titer. In some embodiments, the RNA polynucleotide is present in a dosage of 25-100 micrograms.


Aspects of the invention also provide a unit of use vaccine, comprising between 10 ug and 400 μg of one or more RNA polynucleotides having an open reading frame comprising at least one chemical modification or optionally no modified nucleotides, the open reading frame encoding a first antigenic polypeptide, and a pharmaceutically acceptable carrier or excipient, formulated for delivery to a human subject. In some embodiments, the vaccine further comprises a cationic lipid nanoparticle.


Aspects of the invention provide methods of creating, maintaining or restoring antigenic memory to a virus strain in an individual or population of individuals comprising administering to said individual or population an antigenic memory booster nucleic acid vaccine comprising (a) at least one RNA polynucleotide, said polynucleotide comprising at least one chemical modification or optionally no modified nucleotides and two or more codon-optimized open reading frames, said open reading frames encoding a set of reference antigenic polypeptides, and (b) optionally a pharmaceutically acceptable carrier or excipient. In some embodiments, the vaccine is administered to the individual via a route selected from the group consisting of intramuscular administration, intradermal administration and subcutaneous administration. In some embodiments, the administering step comprises contacting a muscle tissue of the subject with a device suitable for injection of the composition. In some embodiments, the administering step comprises contacting a muscle tissue of the subject with a device suitable for injection of the composition in combination with electroporation.


Aspects of the invention provide methods of vaccinating a subject comprising administering to the subject a single dosage of between 25 μg/kg and 400 μg/kg of a nucleic acid vaccine comprising one or more RNA polynucleotides having an open reading frame encoding a first antigenic polypeptide in an effective amount to vaccinate the subject.


Other aspects provide nucleic acid vaccines comprising one or more RNA polynucleotides having an open reading frame comprising at least one chemical modification, the open reading frame encoding a first antigenic polypeptide, wherein the vaccine has at least 10 fold less RNA polynucleotide than is required for an unmodified mRNA vaccine to produce an equivalent antibody titer. In some embodiments, the RNA polynucleotide is present in a dosage of 25-100 micrograms.


Other aspects provide nucleic acid vaccines comprising an LNP formulated RNA polynucleotide having an open reading frame comprising no nucleotide modifications (unmodified), the open reading frame encoding a first antigenic polypeptide, wherein the vaccine has at least 10 fold less RNA polynucleotide than is required for an unmodified mRNA vaccine not formulated in a LNP to produce an equivalent antibody titer. In some embodiments, the RNA polynucleotide is present in a dosage of 25-100 micrograms.


The data presented in the Examples demonstrate significant enhanced immune responses using the formulations of the invention. Both chemically modified and unmodified RNA vaccines are useful according to the invention. Surprisingly, in contrast to prior art reports that it was preferable to use chemically unmodified mRNA formulated in a carrier for the production of vaccines, it is described herein that chemically modified mRNA-LNP vaccines required a much lower effective mRNA dose than unmodified mRNA, i.e., tenfold less than unmodified mRNA when formulated in carriers other than LNP. Both the chemically modified and unmodified RNA vaccines of the invention produce better immune responses than mRNA vaccines formulated in a different lipid carrier.


In other aspects the invention encompasses a method of treating an elderly subject age 60 years or older comprising administering to the subject a nucleic acid vaccine comprising one or more RNA polynucleotides having an open reading frame encoding an virus antigenic polypeptide in an effective amount to vaccinate the subject.


In other aspects the invention encompasses a method of treating a young subject age 17 years or younger comprising administering to the subject a nucleic acid vaccine comprising one or more RNA polynucleotides having an open reading frame encoding an virus antigenic polypeptide in an effective amount to vaccinate the subject.


In other aspects the invention encompasses a method of treating an adult subject comprising administering to the subject a nucleic acid vaccine comprising one or more RNA polynucleotides having an open reading frame encoding an virus antigenic polypeptide in an effective amount to vaccinate the subject.


In some aspects the invention is a method of vaccinating a subject with a combination vaccine including at least two nucleic acid sequences encoding antigens wherein the dosage for the vaccine is a combined therapeutic dosage wherein the dosage of each individual nucleic acid encoding an antigen is a sub therapeutic dosage. In some embodiments, the combined dosage is 25 micrograms of the RNA polynucleotide in the nucleic acid vaccine administered to the subject. In some embodiments, the combined dosage is 100 micrograms of the RNA polynucleotide in the nucleic acid vaccine administered to the subject. In some embodiments the combined dosage is 50 micrograms of the RNA polynucleotide in the nucleic acid vaccine administered to the subject. In some embodiments, the combined dosage is 75 micrograms of the RNA polynucleotide in the nucleic acid vaccine administered to the subject. In some embodiments, the combined dosage is 150 micrograms of the RNA polynucleotide in the nucleic acid vaccine administered to the subject. In some embodiments, the combined dosage is 400 micrograms of the RNA polynucleotide in the nucleic acid vaccine administered to the subject. In some embodiments, the sub therapeutic dosage of each individual nucleic acid encoding an antigen is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 micrograms. In other embodiments the nucleic acid vaccine is chemically modified and in other embodiments the nucleic acid vaccine is not nucleotide modified.


In some embodiments, the RNA polynucleotide is one of SEQ ID NO: 447-457, 459, 461, 491-503, 524-542, or 566-569 and includes at least one chemical modification. In other embodiments, the RNA polynucleotide is one of SEQ ID NO: 447-457, 459, 461, 491-503, 524-542, or 566-569 and does not include any nucleotide modifications, or is unmodified. In yet other embodiments the at least one RNA polynucleotide encodes an antigenic protein of any of SEQ ID NO: 1-444, 458, 460, 462-479, 543-565, or 566-569 and includes at least one chemical modification. In other embodiments the RNA polynucleotide encodes an antigenic protein of any of SEQ ID NO: 1-444, 458, 460, 462-479,543-565, or 566-569 and does not include any nucleotide modifications, or is unmodified.


In preferred aspects, vaccines of the invention (e.g., LNP-encapsulated mRNA vaccines) produce prophylactically- and/or therapeutically-efficacious levels, concentrations and/or titers of antigen-specific antibodies in the blood or serum of a vaccinated subject. As defined herein, the term antibody titer refers to the amount of antigen-specific antibody produces in s subject, e.g., a human subject. In exemplary embodiments, antibody titer is expressed as the inverse of the greatest dilution (in a serial dilution) that still gives a positive result. In exemplary embodiments, antibody titer is determined or measured by enzyme-linked immunosorbent assay (ELISA). In exemplary embodiments, antibody titer is determined or measured by neutralization assay, e.g., by microneutralization assay. In certain aspects, antibody titer measurement is expressed as a ratio, such as 1:40, 1:100, etc.


In exemplary embodiments of the invention, an efficacious vaccine produces an antibody titer of greater than 1:40, greater that 1:100, greater than 1:400, greater than 1:1000, greater than 1:2000, greater than 1:3000, greater than 1:4000, greater than 1:500, greater than 1:6000, greater than 1:7500, greater than 1:10000. In exemplary embodiments, the antibody titer is produced or reached by 10 days following vaccination, by 20 days following vaccination, by 30 days following vaccination, by 40 days following vaccination, or by 50 or more days following vaccination. In exemplary embodiments, the titer is produced or reached following a single dose of vaccine administered to the subject. In other embodiments, the titer is produced or reached following multiple doses, e.g., following a first and a second dose (e.g., a booster dose).


In exemplary aspects of the invention, antigen-specific antibodies are measured in units of μg/ml or are measured in units of IU/L (International Units per liter) or mIU/ml (milli International Units per ml). In exemplary embodiments of the invention, an efficacious vaccine produces >0.5 μg/ml, >0.1 μg/ml, >0.2 μg/ml, >0.35 μg/ml, >0.5 μg/ml, >1 μg/ml, >2 μg/ml, >5 μg/ml or >10 μg/ml. In exemplary embodiments of the invention, an efficacious vaccine produces >10 mIU/ml, >20 mIU/ml, >50 mIU/ml, >100 mIU/ml, >200 mIU/ml, >500 mIU/ml or >1000 mIU/ml. In exemplary embodiments, the antibody level or concentration is produced or reached by 10 days following vaccination, by 20 days following vaccination, by 30 days following vaccination, by 40 days following vaccination, or by 50 or more days following vaccination. In exemplary embodiments, the level or concentration is produced or reached following a single dose of vaccine administered to the subject. In other embodiments, the level or concentration is produced or reached following multiple doses, e.g., following a first and a second dose (e.g., a booster dose.) In exemplary embodiments, antibody level or concentration is determined or measured by enzyme-linked immunosorbent assay (ELISA). In exemplary embodiments, antibody level or concentration is determined or measured by neutralization assay, e.g., by microneutralization assay.


The details of various embodiments of the disclosure are set forth in the description below. Other features, objects, and advantages of the disclosure will be apparent from the description and from the claims.





BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects, features and advantages will be apparent from the following description of particular embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of various embodiments of the invention.



FIG. 1 shows data obtained from an ELISA, demonstrating that vaccination with RNA encoding HA stem protein sequences from different strains induces serum antibodies that bind to diverse panel of recombinant HA (rHA) proteins.



FIG. 2 shows data demonstrating that serum antibody titers obtained from mice vaccinated with a second set of mRNA vaccine antigens induces serum antibodies that bind to a diverse panel of recombinant HA (rHA) proteins.



FIG. 3 shows combining mRNAs encoding HA stem protein from an H1 strain with mRNA encoding HA stem protein from an H3 strain did not result in interference in the immune response to either HA.



FIGS. 4A-4B depict endpoint titers of the pooled serum from animals vaccinated with the test vaccines. In FIG. 4A, the vaccines tested are shown on the x-axis and the binding to HA from each of the different strains of influenza is plotted as an endpoint titer. In FIG. 4B, the vaccines tested are shown on the x-axis, and the endpoint titer to NP protein is plotted.



FIG. 5 shows an examination of functional antibody response through an assessment of the ability of serum to neutralize a panel of HA-pseudotyped viruses.



FIG. 6 shows data plotted as fold induction (sample luminescence/background luminescence) versus serum concentration.



FIG. 7 is a representation of cell-mediated immune responses following mRNA vaccination. Splenocytes were harvested from vaccinated mice and stimulated with a pool of overlapping NP peptides. The % of CD4 or CD8 T cells secreting one of the three cytokines (IFN-γ, IL-2, or TNF-α) is plotted.



FIG. 8 is a representation of cell-mediated immune responses following mRNA vaccination. Splenocytes were harvested from vaccinated mice and stimulated with a pool of overlapping HA peptides. The % of CD4 or CD8 T cells secreting one of the three cytokines (IFN-γ, IL-2, or TNF-α) is plotted.



FIG. 9 shows murine weight loss following challenge with a lethal dose of mouse-adapted HIN1 A/Puerto Rico/8/1934. The percentage of weight lost as compared to baseline was calculated for each animal and was averaged across the group. The group average was plotted over time in days. Error bars represent standard error of the mean. Efficacy of the NIHGen6HASS-foldon+NP combination vaccine was better than that of either the NIHGen6HASS-foldon or NP mRNA vaccine alone.



FIG. 10 shows vaccine efficacy was similar at all vaccine doses, as well as with all co-formulation and co-delivery methods assessed. Following challenge with a lethal dose of mouse-adapted HIN1 A/Puerto Rico/8/1934, the percentage of weight lost as compared to baseline was calculated for each animal and was averaged across the group. The group average was plotted over time in days. Error bars represent standard error of the mean.



FIG. 11A depicts the endpoint titers of the pooled serum from animals vaccinated with the test vaccines. FIG. 11B shows efficacy of the test vaccines (NIHGen6HASS-foldon and NIHGen6HASS-TM2) is similar. Following challenge with a lethal dose of mouse-adapted HIN1 A/Puerto Rico/8/1934, the percentage of group weight lost as compared to baseline was calculated and plotted over time in days.



FIG. 12A shows that serum from mice immunized with mRNA encoding consensus HA antigens from the H1 subtype was able to detectably neutralize the PR8 luciferase virus.



FIG. 12B shows that serum from mice immunized with mRNA encoding H1 subtype consensus HA antigens with a ferritin fusion sequence was able to detectably neutralize the PR8 luciferase virus, except for the Merck_pH1_Con_ferritin mRNA, while serum from mice vaccinated with an mRNA encoding the consensus H3 antigen with a ferritin fusion sequence was not able to neutralize the PR8 luciferase virus.



FIGS. 13A-13B show murine weight loss following challenge with a lethal dose of mouse-adapted H1N1 A/Puerto Rico/8/1934. The percentage of group weight lost as compared to baseline was calculated and plotted over time in days.



FIG. 14 shows the results of neutralization assays performed on a panel of pseudoviruses to assess the breadth of the serum-neutralizing activity elicited by the consensus HA antigens.



FIG. 15A depicts the ELISA endpoint anti-HA antibody titers of the pooled serum from animals vaccinated with the test vaccines. FIG. 15B shows murine survival (left) and weight loss (right) following challenge with a lethal dose of mouse-adapted B/Ann Arbor/1954. The percentage of group survival and weight loss as compared to baseline was calculated and plotted over time in days.



FIGS. 16A-16C show data depicting the NIHGen6HASS-foldon vaccine's robust antibody response as measured by ELISA assay (plates coated with recombinantly-expressed NIHGen6HASS-foldon [HA stem] or NP proteins). FIG. 16A shows titers to HA stem, over time, for four rhesus macaques previously vaccinated with FLUZONE® and boosted a single time with NIHGen6HASS-foldon mRNA vaccine. FIG. 16B depicts titers to HA stem, over time, from four rhesus macaques vaccinated at days 0, 28 and 56 with the same NIHGen6HASS-foldon RNA vaccine. FIG. 16C illustrates antibody titers to NP, over time, for four rhesus macaques vaccinated at days 0, 28 and 56 with the NP mRNA vaccine and shows that the vaccine elicited a robust antibody response to NP.



FIGS. 17A-17B show the results of ELISAs examining the presence of antibody capable of binding to recombinant hemagglutinin (rHA) from a wide variety of influenza strains. FIG. 17A shows the results of rhesus macaques previously vaccinated with FLUZONE® and boosted a single time with NIHGen6HASS-foldon mRNA vaccine, and FIG. 17B shows the results of naive rhesus macaques vaccinated at days 0, 28 and 56 with the same NIHGen6HASS-foldon RNA vaccine.



FIG. 18 is a representation of cell-mediated immune responses following mRNA vaccination. Peripheral blood mononuclear cells were harvested from vaccinated macaques and stimulated with a pool of overlapping NP peptides. The % of CD4 or CD8 T cells secreting one of the three cytokines (IFN-γ, IL-2, or TNF-α) is plotted.



FIG. 19 shows the results of hemagglutination inhibition (HAI) tests. Placebo subjects (targeted to be 25% of each cohort) are included. The data is shown per protocol, and excludes those that did not receive the day 22 injection.



FIG. 20 shows the HAI test kinetics per subject, including the placebo subjects (targeted to be 25% of each cohort).



FIG. 21 shows the results of microneutralization (MN) tests, including placebo subjects (targeted to be 25% of each cohort). The data shown is per protocol, and excludes those that did not receive a day 22 injection.



FIG. 22 shows the MN test kinetics per subject, including the placebo subjects (targeted to be 25% of each cohort).



FIG. 23 is a graph depicting the very strong correlation between HAI and MN. The data includes placebo subjects (targeted to be 25% of each cohort).



FIG. 24A shows murine survival following challenge with a lethal dose of mouse-adapted influenza virus strain HIN1 A/Puerto Rico/8/1934 (PR8) or H3 A/Hong Kong/1/1968 (HK68). FIG. 24B shows murine weight loss following challenge with a lethal dose of mouse-adapted influenza virus strain HIN1 A/Puerto Rico/8/1934 (PR8) or H3 A/Hong Kong/1/1968 (HK68). FIG. 24C shows murine survival following challenge with a lethal dose of HK68 virus. FIG. 24D shows murine weight loss following challenge with a lethal dose of HK68 virus. The percentage of group survival and weight loss as compared to baseline was calculated and plotted over time in days.





DETAILED DESCRIPTION

Embodiments of the present disclosure provide RNA (e.g., mRNA) vaccines that include polynucleotide encoding an influenza virus antigen. Influenza virus RNA vaccines, as provided herein may be used to induce a balanced immune response, comprising both cellular and humoral immunity, without many of the risks associated with DNA vaccination.


In some embodiments, the virus is a strain of Influenza A or Influenza B or combinations thereof. In some embodiments, the strain of Influenza A or Influenza B is associated with birds, pigs, horses, dogs, humans or non-human primates. In some embodiments, the antigenic polypeptide encodes a hemagglutinin protein. In some embodiments, the hemagglutinin protein is H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, H18. In some embodiments, the hemagglutinin protein does not comprise a head domain. In some embodiments, the hemagglutinin protein comprises a portion of the head domain. In some embodiments, the hemagglutinin protein does not comprise a cytoplasmic domain. In some embodiments, the hemagglutinin protein comprises a portion of the cytoplasmic domain. In some embodiments, the truncated hemagglutinin protein comprises a portion of the transmembrane domain. In some embodiments, the amino acid sequence of the hemagglutinin protein comprises at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97% 98%, or 99% identify with any of the amino acid sequences having an amino acid sequence identified by any one of SEQ ID NO: 1-444, 458, 460, 462-479, or 543-561 (see also Tables 7-13 and 26). In some embodiments, the virus is selected from the group consisting of H1N1, H3N2, H7N9, and H10N8. In some embodiments, the antigenic polypeptide is selected from those proteins having an amino acid sequences identified by any one of SEQ ID NO: 1-444, 458, 460, 462-479, or 543-561 (see also Tables 7-13 and 26).


Some embodiments provide influenza vaccines comprising one or more RNA polynucleotides having an open reading frame encoding a hemagglutinin protein and a pharmaceutically acceptable carrier or excipient, formulated within a cationic lipid nanoparticle. In some embodiments, the hemagglutinin protein is selected from H1, H7 and H10. In some embodiments, the RNA polynucleotide further encodes neuraminidase protein. In some embodiments, the hemagglutinin protein is derived from a strain of Influenza A virus or Influenza B virus or combinations thereof. In some embodiments, the Influenza virus is selected from HIN1, H3N2, H7N9, and H10N8.


Some embodiments provide methods of preventing or treating influenza viral infection comprising administering to a subject any of the vaccines described herein. In some embodiments, the antigen specific immune response comprises a T cell response. In some embodiments, the antigen specific immune response comprises a B cell response. In some embodiments, the antigen specific immune response comprises both a T cell response and a B cell response. In some embodiments, the method of producing an antigen specific immune response involves a single administration of the vaccine. In some embodiments, the vaccine is administered to the subject by intradermal, intramuscular injection, subcutaneous injection, intranasal inoculation, or oral administration.


In some embodiments, the RNA (e.g., mRNA) polynucleotides or portions thereof may encode one or more polypeptides of an influenza strain as an antigen. Such antigens include, but are not limited to, those antigens encoded by the polynucleotides or portions thereof of the polynucleotides listed in the Tables presented herein. In the Tables, the GenBank Accession Number or GI Accession Number represents either the complete or partial CDS of the encoded antigen. The RNA (e.g., mRNA) polynucleotides may comprise a region of any of the sequences listed in the Tables or entire coding region of the mRNA listed. They may comprise hybrid or chimeric regions, or mimics or variants.


In the following embodiments, when referring to at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding for a specific influenza virus protein, the polynucleotides may comprise a coding region of the specific influenza virus protein sequence or the entire coding region of the mRNA for that specific influenza virus protein sequence.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (e.g., at least one HA1, HA2, or a combination of both, of H1-H18).


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (e.g., at least one HA1, HA2, or a combination of both, of H1-H18) and at least one protein selected from a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein and a NS2 protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (e.g., at least one of H1-H18) and at least two proteins selected from a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein and a NS2 protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (e.g., at least one of H1-H18) and at least three proteins selected from a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein and a NS2 protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (e.g., at least one of H1-H18) and at least four proteins selected from a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein and a NS2 protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (e.g., at least one of H1-H18) and at least five proteins selected from a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein and a NS2 protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (e.g., at least one of H1-H18), a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, and a NS2 protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein and a NA protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein and a M1 protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein and a M2 protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein and a NS1 protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein and a NS2 protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein, a NP protein and a NA protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein, a NP protein, and a M1 protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein, a NP protein, and a M2 protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein, a NP protein, and a NS1 protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein, a NP protein, and a NS2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein, a NA protein, and a M1 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein, a NA protein, and a M2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein, a NA protein, and a NS1 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein, a NA protein, and a NS2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein, a M1 protein, and a M2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein, a M1 protein, and a NS1 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein, a M1 protein, and a NS2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein, a M2 protein, and a NS1 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein, a M2 protein, and a NS2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein, a NS1 protein, and a NS2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA1 protein, and a NA protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA1 protein and a M1 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA1 protein and a M2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA1 protein and a NS1 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA1 protein and a NS2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA1 protein, a NP protein, and a NA protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA1 protein, a NP protein, and a M1 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA1 protein, a NP protein, and a M2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA1 protein, a NP protein, and a NS1 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA1 protein, a NP protein, and a NS2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA1 protein, a NA protein, and a M1 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA1 protein, a NA protein, and a M2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA1 protein, a NA protein and a NS1 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA1 protein, a NA protein, and a NS2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA1 protein, a M1 protein, and a M2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA1 protein, a M1 protein, and a NS1 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA1 protein, a M1 protein, and a NS2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA1 protein, a M2 protein, and a NS1 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA1 protein, a M2 protein, and a NS2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA1 protein, a NS1 protein, and a NS2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2), and a NA protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2) and a M1 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2) and a M2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2) and a NS1 protein obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2) and a NS2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2), a NP protein, and a NA protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2), a NP protein, and a M1 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2), a NP protein, and a M2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2), a NP protein, and a NS1 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2), a NP protein and a NS2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2), a NA protein, and a M1 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2), a NA protein, and a M2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2), a NA protein, and a NS1 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2), a NA protein, and a NS2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2), a M1 protein, and a M2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2), a M1 protein, and a NS1 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2), a M1 protein, and a NS2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2), a M2 protein, and a NS1 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a H HA protein (HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2), a M2 protein, and a NS2 protein, obtained from influenza virus.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a HA protein (HA or derivatives thereof comprising antigenic sequences from HA1 and/or HA2), a NS1 protein, and a NS2 protein, obtained from influenza virus.


It should be understood that the present disclosure is not intended to be limited by a particular strain of influenza virus. The strain of influenza virus used, as provided herein, may be any strain of influenza virus. Examples of preferred strains of influenza virus and preferred influenza antigens are provided in Tables 7-13 below.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding an influenza antigenic polypeptide (e.g., a HA protein, a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a NS2 protein, an immunogenic fragment of any of the foregoing influenza antigens, a variant or homolog of any of the foregoing influenza antigens, or any combination of two or more of the foregoing influenza antigens, variants or homologs) obtained from H1/PuertoRico/8/1934.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding an influenza antigenic polypeptide (e.g., a HA protein, a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a NS2 protein, an immunogenic fragment of any of the foregoing influenza antigens, a variant or homolog of any of the foregoing influenza antigens, or any combination of two or more of the foregoing influenza antigens, variants or homologs) obtained from H1/New Caledonia/20/1999.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding an influenza antigenic polypeptide (e.g., a HA protein, a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a NS2 protein, an immunogenic fragment of any of the foregoing influenza antigens, a variant or homolog of any of the foregoing influenza antigens, or any combination of two or more of the foregoing influenza antigens, variants or homologs) obtained from H1/California/04/2009.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding an influenza antigenic polypeptide (e.g., a HA protein, a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a NS2 protein, an immunogenic fragment of any of the foregoing influenza antigens, a variant or homolog of any of the foregoing influenza antigens, or any combination of two or more of the foregoing influenza antigens, variants or homologs) obtained from H5/Vietnam/1194/2004.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding an influenza antigenic polypeptide (e.g., a HA protein, a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a NS2 protein, an immunogenic fragment of any of the foregoing influenza antigens, a variant or homolog of any of the foregoing influenza antigens, or any combination of two or more of the foregoing influenza antigens, variants or homologs) obtained from H2/Japan/305/1957.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding an influenza antigenic polypeptide (e.g., a HA protein, a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a NS2 protein, an immunogenic fragment of any of the foregoing influenza antigens, a variant or homolog of any of the foregoing influenza antigens, or any combination of two or more of the foregoing influenza antigens, variants or homologs) obtained from H9/Hong Kong/1073/99.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding an influenza antigenic polypeptide (e.g., a HA protein, a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a NS2 protein, an immunogenic fragment of any of the foregoing influenza antigens, a variant or homolog of any of the foregoing influenza antigens, or any combination of two or more of the foregoing influenza antigens, variants or homologs) obtained from H3/Aichi/2/1968.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding an influenza antigenic polypeptide (e.g., a HA protein, a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a NS2 protein, an immunogenic fragment of any of the foregoing influenza antigens, a variant or homolog of any of the foregoing influenza antigens, or any combination of two or more of the foregoing influenza antigens, variants or homologs) obtained from H3/Brisbane/10/2007.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding an influenza antigenic polypeptide (e.g., a HA protein, a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a NS2 protein, an immunogenic fragment of any of the foregoing influenza antigens, a variant or homolog of any of the foregoing influenza antigens, or any combination of two or more of the foregoing influenza antigens, variants or homologs) obtained from H7/Anhui/1/2013.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding an influenza antigenic polypeptide (e.g., a HA protein, a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a NS2 protein, an immunogenic fragment of any of the foregoing influenza antigens, a variant or homolog of any of the foregoing influenza antigens, or any combination of two or more of the foregoing influenza antigens, variants or homologs) obtained from H10/Jiangxi-Donghu/346/2013.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding an influenza antigenic polypeptide (e.g., a HA protein, a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a NS2 protein, an immunogenic fragment of any of the foregoing influenza antigens, a variant or homolog of any of the foregoing influenza antigens, or any combination of two or more of the foregoing influenza antigens, variants or homologs) obtained from H3/Wisconsin/67/2005.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding an influenza antigenic polypeptide (e.g., a HA protein, a NP protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a NS2 protein, an immunogenic fragment of any of the foregoing influenza antigens, a variant or homolog of any of the foregoing influenza antigens, or any combination of two or more of the foregoing influenza antigens, variants or homologs) obtained from H1/Vietnam/850/2009.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding influenza H7N9 HA1 protein, ferritin and a dendritic cell targeting peptide (see, e.g., Ren X et al. Emerg Infect Dis 2013; 19(11):1881-84; Steel J et al. mBio 2010; 1(1): e00018-10; Kanekiyo M. et al. Nature 2013; 499:102-6, each of which is incorporated herein by reference).


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding an avian influenza H7 HA protein.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding influenza H7 HA1 protein (see, e.g., Steel J et al. mBio 2010; 1(1):e00018-10).


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding influenza H7N9 HA1 protein and ferritin (see, e.g., Kanekiyo M. et al. Nature 2013; 499:102-6).


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding an influenza H5N1 protein. In some embodiments, the influenza H5N1 protein is from a human strain.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding an influenza H1N1 protein.


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding an influenza protein from an influenza A strain, such as human HIN1, H5N1, H9N2 or H3N2. In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding an influenza H1N1 HA having a nanoscaffold (see, e.g., Walker A et al. Sci Rep 2011:1(5):1-8, incorporated herein by reference).


In some embodiments, a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a glycosylated influenza HIN1 HA (see, e.g., Chen J et al. PNAS USA 2014; 111(7):2476-81, incorporated herein by reference).


An influenza vaccine may comprise, for example, at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding at least one influenza HA2 stem antigen selected from the influenza HA2 stem antigens, provided herein, for example, those listed in Table 16, comprising an amino acid sequence identified by any one of SEQ ID NO: 394-412.


The present disclosure also encompasses an influenza vaccine comprising, for example, at least one RNA (e.g., mRNA) polynucleotide having a nucleic acid sequence selected from the influenza sequences listed in SEQ ID NO: 491-503 or 566-569 (see also: Mallajosyula V V et al., Front Immunol. 2015 Jun. 26; 6:329; Mallajosyula V V et al., Proc Natl Acad Sci USA. 2014 Jun. 24; 111(25):E2514-23; Bommakanti G, et al., J Virol. 2012 December; 86(24):13434-44; Bommakanti G et al., Proc Natl Acad Sci USA. 2010 Aug. 3; 107(31):13701-6 and Yassine et al., Nat Med. 2015 September; 21(9):1065-70; Impagliazzo et al., Science, 2015 Sep. 18; 349(6254)).


The entire contents of International Application No. PCT/US2015/027400, International Publication No. WO2015/164674A, is incorporated herein by reference.


In some embodiments the vaccines described herein are consensus sequences. A “consensus sequence” as used herein refers to a polypeptide sequence based on analysis of an alignment of multiple subtypes of a particular influenza antigen. mRNA sequences that encode a consensus polypeptide sequence may be prepared and used to induce broad immunity against multiple subtypes or serotypes of a particular influenza antigen.


The mRNA encoding influenza antigens provided herein can be arranged as a vaccine that causes seroconversion in vaccinated mammals and provides cross-reactivity against a broad range of seasonal strains of influenza and also pandemic strains of influenza. The seroconversion and broad cross-reactivity can be determined by measuring inhibiting titers against different hemagglutinin strains of influenza. Preferred combinations include at least two antigens from each of the influenza antigens described herein.


It has been discovered that the mRNA vaccines described herein are superior to current vaccines in several ways. First, the lipid nanoparticle (LNP) delivery is superior to other formulations including a protamine base approach described in the literature and no additional adjuvants are to be necessary. The use of LNPs enables the effective delivery of chemically modified or unmodified mRNA vaccines. Additionally it has been demonstrated herein that both modified and unmodified LNP formulated mRNA vaccines were superior to conventional vaccines by a significant degree. In some embodiments the mRNA vaccines of the invention are superior to conventional vaccines by a factor of at least 10 fold, 20 fold, 40 fold, 50 fold, 100 fold, 500 fold or 1,000 fold.


Although attempts have been made to produce functional RNA vaccines, including mRNA vaccines and self-replicating RNA vaccines, the therapeutic efficacy of these RNA vaccines have not yet been fully established. Quite surprisingly, the inventors have discovered, according to aspects of the invention a class of formulations for delivering mRNA vaccines in vivo that results in significantly enhanced, and in many respects synergistic, immune responses including enhanced antigen generation and functional antibody production with neutralization capability. These results can be achieved even when significantly lower doses of the mRNA are administered in comparison with mRNA doses used in other classes of lipid based formulations. The formulations of the invention have demonstrated significant unexpected in vivo immune responses sufficient to establish the efficacy of functional mRNA vaccines as prophylactic and therapeutic agents. Additionally, self-replicating RNA vaccines rely on viral replication pathways to deliver enough RNA to a cell to produce an immunogenic response. The formulations of the invention do not require viral replication to produce enough protein to result in a strong immune response. Thus, the mRNA of the invention are not self-replicating RNA and do not include components necessary for viral replication.


The invention involves, in some aspects, the surprising finding that lipid nanoparticle (LNP) formulations significantly enhance the effectiveness of mRNA vaccines, including chemically modified and unmodified mRNA vaccines. The efficacy of mRNA vaccines formulated in LNP was examined in vivo using several distinct antigens. The results presented herein demonstrate the unexpected superior efficacy of the mRNA vaccines formulated in LNP over other commercially available vaccines.


In addition to providing an enhanced immune response, the formulations of the invention generate a more rapid immune response with fewer doses of antigen than other vaccines tested. The mRNA-LNP formulations of the invention also produce quantitatively and qualitatively better immune responses than vaccines formulated in a different carriers.


The data described herein demonstrate that the formulations of the invention produced significant unexpected improvements over existing antigen vaccines. Additionally, the mRNA-LNP formulations of the invention are superior to other vaccines even when the dose of mRNA is lower than other vaccines. mRNA encoding HA protein sequences such as HA stem sequences from different strains have been demonstrated to induce serum antibodies that bind to diverse panel of recombinant HA (rHA) proteins. The vaccine efficacy in mice was similar at all vaccine doses, as well as with all co-formulation and co-delivery methods assessed.


The LNP used in the studies described herein has been used previously to deliver siRNA in various animal models as well as in humans. In view of the observations made in association with the siRNA delivery of LNP formulations, the fact that LNP is useful in vaccines is quite surprising. It has been observed that therapeutic delivery of siRNA formulated in LNP causes an undesirable inflammatory response associated with a transient IgM response, typically leading to a reduction in antigen production and a compromised immune response. In contrast to the findings observed with siRNA, the LNP-mRNA formulations of the invention are demonstrated herein to generate enhanced IgG levels, sufficient for prophylactic and therapeutic methods rather than transient IgM responses.


Nucleic Acids/Polynucleotides

Influenza virus vaccines, as provided herein, comprise at least one (one or more) ribonucleic acid (RNA) (e.g., mRNA) polynucleotide having an open reading frame encoding at least one Influenza antigenic polypeptide. The term “nucleic acid” includes any compound and/or substance that comprises a polymer of nucleotides (nucleotide monomer). These polymers are referred to as polynucleotides. Thus, the terms “nucleic acid” and “polynucleotide” are used interchangeably.


Nucleic acids may be or may include, for example, ribonucleic acids (RNAs), deoxyribonucleic acids (DNAs), threose nucleic acids (TNAs), glycol nucleic acids (GNAs), peptide nucleic acids (PNAs), locked nucleic acids (LNAs, including LNA having a β-D-ribo configuration, α-LNA having an α-L-ribo configuration (a diastereomer of LNA), 2′-amino-LNA having a 2′-amino functionalization, and 2′-amino-α-LNA having a 2′-amino functionalization), ethylene nucleic acids (ENA), cyclohexenyl nucleic acids (CeNA) or chimeras or combinations thereof.


In some embodiments, polynucleotides of the present disclosure function as messenger RNA (mRNA). “Messenger RNA” (mRNA) refers to any polynucleotide that encodes a (at least one) polypeptide (a naturally-occurring, non-naturally-occurring, or modified polymer of amino acids) and can be translated to produce the encoded polypeptide in vitro, in vivo, in situ or ex vivo. The skilled artisan will appreciate that, except where otherwise noted, polynucleotide sequences set forth in the instant application will recite “T” s in a representative DNA sequence but where the sequence represents RNA (e.g., mRNA), the “T”s would be substituted for “U” s. Thus, any of the RNA polynucleotides encoded by a DNA identified by a particular sequence identification number may also comprise the corresponding RNA (e.g., mRNA) sequence encoded by the DNA, where each “T” of the DNA sequence is substituted with “U.”


It should be understood that the mRNA polynucleotides of the vaccines as provided herein are synthetic molecules, i.e., they are not naturally-occurring molecules. That is, the mRNA polynucleotides of the present disclosure are isolated mRNA polynucleotides. As is known in the art, “isolated polynucleotides” refer to polynucleotides that are substantially physically separated from other cellular material (e.g., separated from cells and/or systems that produce the polynucleotides) or from other material that hinders their use in the vaccines of the present disclosure. Isolated polynucleotides are substantially pure in that they have been substantially separated from the substances with which they may be associated in living or viral systems. Thus, mRNA polynucleotide vaccines are not associated with living or viral systems, such as cells or viruses. The mRNA polynucleotide vaccines do not include viral components (e.g., viral capsids, viral enzymes, or other viral proteins, for example, those needed for viral-based replication), and the mRNA polynucleotide vaccines are not packaged within, encapsulated within, linked to, or otherwise associated with a virus or viral particle. In some embodiments, the mRNA vaccines comprise a lipid nanoparticle that consists of, or consists essentially of, one or more mRNA polynucleotides (e.g., mRNA polynucleotides encoding one or more influenza antigen(s)).


The basic components of an mRNA molecule typically include at least one coding region, a 5′ untranslated region (UTR), a 3′ UTR, a 5′ cap and a poly-A tail. Polynucleotides of the present disclosure may function as mRNA but can be distinguished from wild-type mRNA in their functional and/or structural design features, which serve to overcome existing problems of effective polypeptide expression using nucleic-acid based therapeutics. In some embodiments, the RNA is a mRNA having an open reading frame encoding at least one influenza virus antigen. In some embodiments, the RNA (e.g., mRNA) further comprises a (at least one) 5′ UTR, 3′ UTR, a polyA tail and/or a 5′ cap.


In some embodiments, a RNA polynucleotide of an RNA (e.g., mRNA) vaccine encodes 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10, 5-9, 5-8, 5-7, 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8-10, 8-9 or 9-10 antigenic polypeptides. In some embodiments, a RNA (e.g., mRNA) polynucleotide of an influenza vaccine encodes at least 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100 antigenic polypeptides. In some embodiments, a RNA (e.g., mRNA) polynucleotide of an influenza vaccine encodes at least 100 or at least 200 antigenic polypeptides. In some embodiments, a RNA polynucleotide of an influenza vaccine encodes 1-10, 5-15, 10-20, 15-25, 20-30, 25-35, 30-40, 35-45, 40-50, 1-50, 1-100, 2-50 or 2-100 antigenic polypeptides.


Polynucleotides of the present disclosure, in some embodiments, are codon optimized. Codon optimization methods are known in the art and may be used as provided herein. Codon optimization, in some embodiments, may be used to match codon frequencies in target and host organisms to ensure proper folding; bias GC content to increase mRNA stability or reduce secondary structures; minimize tandem repeat codons or base runs that may impair gene construction or expression; customize transcriptional and translational control regions; insert or remove protein trafficking sequences; remove/add post translation modification sites in encoded protein (e.g. glycosylation sites); add, remove or shuffle protein domains; insert or delete restriction sites; modify ribosome binding sites and mRNA degradation sites; adjust translational rates to allow the various domains of the protein to fold properly; or to reduce or eliminate problem secondary structures within the polynucleotide. Codon optimization tools, algorithms and services are known in the art—non-limiting examples include services from GeneArt (Life Technologies), DNA2.0 (Menlo Park CA) and/or proprietary methods. In some embodiments, the open reading frame (ORF) sequence is optimized using optimization algorithms.


In some embodiments, a codon optimized sequence shares less than 95% sequence identity, less than 90% sequence identity, less than 85% sequence identity, less than 80% sequence identity, or less than 75% sequence identity to a naturally-occurring or wild-type sequence (e.g., a naturally-occurring or wild-type mRNA sequence encoding a polypeptide or protein of interest (e.g., an antigenic protein or antigenic polypeptide)).


In some embodiments, a codon-optimized sequence shares between 65% and 85% (e.g., between about 67% and about 85%, or between about 67% and about 80%) sequence identity to a naturally-occurring sequence or a wild-type sequence (e.g., a naturally-occurring or wild-type mRNA sequence encoding a polypeptide or protein of interest (e.g., an antigenic protein or polypeptide)). In some embodiments, a codon-optimized sequence shares between 65% and 75%, or about 80% sequence identity to a naturally-occurring sequence or wild-type sequence (e.g., a naturally-occurring or wild-type mRNA sequence encoding a polypeptide or protein of interest (e.g., an antigenic protein or polypeptide)).


In some embodiments a codon-optimized RNA (e.g., mRNA) may, for instance, be one in which the levels of G/C are enhanced. The G/C-content of nucleic acid molecules may influence the stability of the RNA. RNA having an increased amount of guanine (G) and/or cytosine (C) residues may be functionally more stable than nucleic acids containing a large amount of adenine (A) and thymine (T) or uracil (U) nucleotides. WO2002/098443 discloses a pharmaceutical composition containing an mRNA stabilized by sequence modifications in the translated region. Due to the degeneracy of the genetic code, the modifications work by substituting existing codons for those that promote greater RNA stability without changing the resulting amino acid. The approach is limited to coding regions of the RNA.


Antigens/Antigenic Polypeptides

In some embodiments, an antigenic polypeptide (e.g., at least one Influenza antigenic polypeptide) is longer than 25 amino acids and shorter than 50 amino acids. The term “antigenic polypeptides” and “antigenic proteins” includes immunogenic fragments and epitopes thereof (e.g., an immunogenic fragment capable of inducing an immune response to influenza). Polypeptides include gene products, naturally occurring polypeptides, synthetic polypeptides, homologs, orthologs, paralogs, fragments and other equivalents, variants, and analogs of the foregoing. A polypeptide may be a single molecule or may be a multi-molecular complex such as a dimer, trimer or tetramer. Polypeptides may also comprise single chain polypeptides or multichain polypeptides, such as antibodies or insulin, and may be associated or linked to each other. Most commonly, disulfide linkages are found in multichain polypeptides. The term “polypeptide” may also apply to amino acid polymers in which at least one amino acid residue is an artificial chemical analogue of a corresponding naturally-occurring amino acid.


A “polypeptide variant” is a molecule that differs in its amino acid sequence relative to a native sequence or a reference sequence. Amino acid sequence variants may possess substitutions, deletions, insertions, or a combination of any two or three of the foregoing, at certain positions within the amino acid sequence, as compared to a native sequence or a reference sequence. Ordinarily, variants possess at least 50% identity to a native sequence or a reference sequence. In some embodiments, variants share at least 80% identity or at least 90% identity with a native sequence or a reference sequence.


In some embodiments “variant mimics” are provided. A “variant mimic” contains at least one amino acid that would mimic an activated sequence. For example, glutamate may serve as a mimic for phosphoro-threonine and/or phosphoro-serine. Alternatively, variant mimics may result in deactivation or in an inactivated product containing the mimic. For example, phenylalanine may act as an inactivating substitution for tyrosine, or alanine may act as an inactivating substitution for serine.


“Orthologs” refers to genes in different species that evolved from a common ancestral gene by speciation. Normally, orthologs retain the same function in the course of evolution. Identification of orthologs is important for reliable prediction of gene function in newly sequenced genomes.


“Analogs” is meant to include polypeptide variants that differ by one or more amino acid alterations, for example, substitutions, additions or deletions of amino acid residues that still maintain one or more of the properties of the parent or starting polypeptide.


The present disclosure provides several types of compositions that are polynucleotide or polypeptide based, including variants and derivatives. These include, for example, substitutional, insertional, deletion and covalent variants and derivatives. The term “derivative” is synonymous with the term “variant” and generally refers to a molecule that has been modified and/or changed in any way relative to a reference molecule or a starting molecule.


As such, polynucleotides encoding peptides or polypeptides containing substitutions, insertions and/or additions, deletions and covalent modifications with respect to reference sequences, in particular the polypeptide sequences disclosed herein, are included within the scope of this disclosure. For example, sequence tags or amino acids, such as one or more lysines, can be added to peptide sequences (e.g., at the N-terminal or C-terminal ends). Sequence tags can be used for peptide detection, purification or localization. Lysines can be used to increase peptide solubility or to allow for biotinylation. Alternatively, amino acid residues located at the carboxy and amino terminal regions of the amino acid sequence of a peptide or protein may optionally be deleted providing for truncated sequences. Certain amino acids (e.g., C-terminal residues or N-terminal residues) alternatively may be deleted depending on the use of the sequence, as for example, expression of the sequence as part of a larger sequence that is soluble, or linked to a solid support.


“Substitutional variants” when referring to polypeptides are those that have at least one amino acid residue in a native or starting sequence removed and a different amino acid inserted in its place at the same position. Substitutions may be single, where only one amino acid in the molecule has been substituted, or they may be multiple, where two or more (e.g., 3, 4 or 5) amino acids have been substituted in the same molecule.


As used herein the term “conservative amino acid substitution” refers to the substitution of an amino acid that is normally present in the sequence with a different amino acid of similar size, charge, or polarity. Examples of conservative substitutions include the substitution of a non-polar (hydrophobic) residue such as isoleucine, valine and leucine for another non-polar residue. Likewise, examples of conservative substitutions include the substitution of one polar (hydrophilic) residue for another such as between arginine and lysine, between glutamine and asparagine, and between glycine and serine. Additionally, the substitution of a basic residue such as lysine, arginine or histidine for another, or the substitution of one acidic residue such as aspartic acid or glutamic acid for another acidic residue are additional examples of conservative substitutions. Examples of non-conservative substitutions include the substitution of a non-polar (hydrophobic) amino acid residue such as isoleucine, valine, leucine, alanine, methionine for a polar (hydrophilic) residue such as cysteine, glutamine, glutamic acid or lysine and/or a polar residue for a non-polar residue.


“Features” when referring to polypeptide or polynucleotide are defined as distinct amino acid sequence-based or nucleotide-based components of a molecule respectively. Features of the polypeptides encoded by the polynucleotides include surface manifestations, local conformational shape, folds, loops, half-loops, domains, half-domains, sites, termini and any combination(s) thereof.


As used herein when referring to polypeptides the term “domain” refers to a motif of a polypeptide having one or more identifiable structural or functional characteristics or properties (e.g., binding capacity, serving as a site for protein-protein interactions).


As used herein when referring to polypeptides the terms “site” as it pertains to amino acid based embodiments is used synonymously with “amino acid residue” and “amino acid side chain.” As used herein when referring to polynucleotides the terms “site” as it pertains to nucleotide based embodiments is used synonymously with “nucleotide.” A site represents a position within a peptide or polypeptide or polynucleotide that may be modified, manipulated, altered, derivatized or varied within the polypeptide-based or polynucleotide-based molecules.


As used herein the terms “termini” or “terminus” when referring to polypeptides or polynucleotides refers to an extremity of a polypeptide or polynucleotide respectively. Such extremity is not limited only to the first or final site of the polypeptide or polynucleotide but may include additional amino acids or nucleotides in the terminal regions. Polypeptide-based molecules may be characterized as having both an N-terminus (terminated by an amino acid with a free amino group (NH2)) and a C-terminus (terminated by an amino acid with a free carboxyl group (COOH)). Proteins are in some cases made up of multiple polypeptide chains brought together by disulfide bonds or by non-covalent forces (multimers, oligomers). These proteins have multiple N- and C-termini. Alternatively, the termini of the polypeptides may be modified such that they begin or end, as the case may be, with a non-polypeptide based moiety such as an organic conjugate.


As recognized by those skilled in the art, protein fragments, functional protein domains, and homologous proteins are also considered to be within the scope of polypeptides of interest. For example, provided herein is any protein fragment (meaning a polypeptide sequence at least one amino acid residue shorter than a reference polypeptide sequence but otherwise identical) of a reference protein having a length of 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 or longer than 100 amino acids. In another example, any protein that includes a stretch of 20, 30, 40, 50, or 100 (contiguous) amino acids that are 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 100% identical to any of the sequences described herein can be utilized in accordance with the disclosure. In some embodiments, a polypeptide includes 2, 3, 4, 5, 6, 7, 8, 9, 10, or more mutations as shown in any of the sequences provided herein or referenced herein. In another example, any protein that includes a stretch of 20, 30, 40, 50, or 100 amino acids that are greater than 80%, 90%, 95%, or 100% identical to any of the sequences described herein, wherein the protein has a stretch of 5, 10, 15, 20, 25, or 30 amino acids that are less than 80%, 75%, 70%, 65% to 60% identical to any of the sequences described herein can be utilized in accordance with the disclosure.


Polypeptide or polynucleotide molecules of the present disclosure may share a certain degree of sequence similarity or identity with the reference molecules (e.g., reference polypeptides or reference polynucleotides), for example, with art-described molecules (e.g., engineered or designed molecules or wild-type molecules). The term “identity,” as known in the art, refers to a relationship between the sequences of two or more polypeptides or polynucleotides, as determined by comparing the sequences. In the art, identity also means the degree of sequence relatedness between two sequences as determined by the number of matches between strings of two or more amino acid residues or nucleic acid residues. Identity measures the percent of identical matches between the smaller of two or more sequences with gap alignments (if any) addressed by a particular mathematical model or computer program (e.g., “algorithms”). Identity of related peptides can be readily calculated by known methods. “% identity” as it applies to polypeptide or polynucleotide sequences is defined as the percentage of residues (amino acid residues or nucleic acid residues) in the candidate amino acid or nucleic acid sequence that are identical with the residues in the amino acid sequence or nucleic acid sequence of a second sequence after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent identity. Methods and computer programs for the alignment are well known in the art. Identity depends on a calculation of percent identity but may differ in value due to gaps and penalties introduced in the calculation. Generally, variants of a particular polynucleotide or polypeptide have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% but less than 100% sequence identity to that particular reference polynucleotide or polypeptide as determined by sequence alignment programs and parameters described herein and known to those skilled in the art. Such tools for alignment include those of the BLAST suite (Stephen F. Altschul, et al. (1997).” Gapped BLAST and PSI-BLAST: a new generation of protein database search programs,” Nucleic Acids Res. 25:3389-3402). Another popular local alignment technique is based on the Smith-Waterman algorithm (Smith, T. F. & Waterman, M. S. (1981) “Identification of common molecular subsequences.” J. Mol. Biol. 147:195-197). A general global alignment technique based on dynamic programming is the Needleman-Wunsch algorithm (Needleman, S. B. & Wunsch, C. D. (1970) “A general method applicable to the search for similarities in the amino acid sequences of two proteins.” J. Mol. Biol. 48:443-453). More recently, a Fast Optimal Global Sequence Alignment Algorithm (FOGSAA) was developed that purportedly produces global alignment of nucleotide and protein sequences faster than other optimal global alignment methods, including the Needleman-Wunsch algorithm. Other tools are described herein, specifically in the definition of “identity” below.


As used herein, the term “homology” refers to the overall relatedness between polymeric molecules, e.g. between nucleic acid molecules (e.g. DNA molecules and/or RNA molecules) and/or between polypeptide molecules. Polymeric molecules (e.g. nucleic acid molecules (e.g. DNA molecules and/or RNA molecules) and/or polypeptide molecules) that share a threshold level of similarity or identity determined by alignment of matching residues are termed homologous. Homology is a qualitative term that describes a relationship between molecules and can be based upon the quantitative similarity or identity. Similarity or identity is a quantitative term that defines the degree of sequence match between two compared sequences. In some embodiments, polymeric molecules are considered to be “homologous” to one another if their sequences are at least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical or similar. The term “homologous” necessarily refers to a comparison between at least two sequences (polynucleotide or polypeptide sequences). Two polynucleotide sequences are considered homologous if the polypeptides they encode are at least 50%, 60%, 70%, 80%, 90%, 95%, or even 99% for at least one stretch of at least 20 amino acids. In some embodiments, homologous polynucleotide sequences are characterized by the ability to encode a stretch of at least 4-5 uniquely specified amino acids. For polynucleotide sequences less than 60 nucleotides in length, homology is determined by the ability to encode a stretch of at least 4-5 uniquely specified amino acids. Two protein sequences are considered homologous if the proteins are at least 50%, 60%, 70%, 80%, or 90% identical for at least one stretch of at least 20 amino acids.


Homology implies that the compared sequences diverged in evolution from a common origin. The term “homolog” refers to a first amino acid sequence or nucleic acid sequence (e.g., gene (DNA or RNA) or protein sequence) that is related to a second amino acid sequence or nucleic acid sequence by descent from a common ancestral sequence. The term “homolog” may apply to the relationship between genes and/or proteins separated by the event of speciation or to the relationship between genes and/or proteins separated by the event of genetic duplication. “Orthologs” are genes (or proteins) in different species that evolved from a common ancestral gene (or protein) by speciation. Typically, orthologs retain the same function in the course of evolution. “Paralogs” are genes (or proteins) related by duplication within a genome. Orthologs retain the same function in the course of evolution, whereas paralogs evolve new functions, even if these are related to the original one.


The term “identity” refers to the overall relatedness between polymeric molecules, for example, between polynucleotide molecules (e.g. DNA molecules and/or RNA molecules) and/or between polypeptide molecules. Calculation of the percent identity of two polynucleic acid sequences, for example, can be performed by aligning the two sequences for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second nucleic acid sequences for optimal alignment and non-identical sequences can be disregarded for comparison purposes). In certain embodiments, the length of a sequence aligned for comparison purposes is at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the length of the reference sequence. The nucleotides at corresponding nucleotide positions are then compared. When a position in the first sequence is occupied by the same nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position. The percent identity between the two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps, and the length of each gap, which needs to be introduced for optimal alignment of the two sequences. The comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm. For example, the percent identity between two nucleic acid sequences can be determined using methods such as those described in Computational Molecular Biology, Lesk, A. M., ed., Oxford University Press, New York, 1988; Biocomputing: Informatics and Genome Projects, Smith, D. W., ed., Academic Press, New York, 1993; Sequence Analysis in Molecular Biology, von Heinje, G., Academic Press, 1987; Computer Analysis of Sequence Data, Part I, Griffin, A. M., and Griffin, H. G., eds., Humana Press, New Jersey, 1994; and Sequence Analysis Primer, Gribskov, M. and Devereux, J., eds., M Stockton Press, New York, 1991; each of which is incorporated herein by reference. For example, the percent identity between two nucleic acid sequences can be determined using the algorithm of Meyers and Miller (CABIOS, 1989, 4:11-17), which has been incorporated into the ALIGN program (version 2.0) using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. The percent identity between two nucleic acid sequences can, alternatively, be determined using the GAP program in the GCG software package using an NWSgapdna.CMP matrix. Methods commonly employed to determine percent identity between sequences include, but are not limited to those disclosed in Carillo, H., and Lipman, D., SIAM J Applied Math., 48:1073 (1988); incorporated herein by reference. Techniques for determining identity are codified in publicly available computer programs. Exemplary computer software to determine homology between two sequences include, but are not limited to, GCG program package, Devereux, J., et al., Nucleic Acids Research, 12, 387 (1984)), BLASTP, BLASTN, and FASTA Altschul, S. F. et al., J. Molec. Biol., 215, 403 (1990)).


Multiprotein and Multicomponent Vaccines

The present disclosure encompasses influenza vaccines comprising multiple RNA (e.g., mRNA) polynucleotides, each encoding a single antigenic polypeptide, as well as influenza vaccines comprising a single RNA polynucleotide encoding more than one antigenic polypeptide (e.g., as a fusion polypeptide). Thus, a vaccine composition comprising a RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a first antigenic polypeptide and a RNA (e.g., mRNA) polynucleotide having an open reading frame encoding a second antigenic polypeptide encompasses (a) vaccines that comprise a first RNA polynucleotide encoding a first antigenic polypeptide and a second RNA polynucleotide encoding a second antigenic polypeptide, and (b) vaccines that comprise a single RNA polynucleotide encoding a first and second antigenic polypeptide (e.g., as a fusion polypeptide). RNA (e.g., mRNA) vaccines of the present disclosure, in some embodiments, comprise 2-10 (e.g., 2, 3, 4, 5, 6, 7, 8, 9 or 10), or more, RNA polynucleotides having an open reading frame, each of which encodes a different antigenic polypeptide (or a single RNA polynucleotide encoding 2-10, or more, different antigenic polypeptides). The antigenic polypeptides may be selected from any of the influenza antigenic polypeptides described herein.


In some embodiments, a multicomponent vaccine comprises at least one RNA (e.g., mRNA) polynucleotide encoding at least one influenza antigenic polypeptide fused to a signal peptide (e.g., SEQ ID NO: 488-490). The signal peptide may be fused at the N-terminus or the C-terminus of an antigenic polypeptide.


Signal Peptides

In some embodiments, antigenic polypeptides encoded by influenza RNA (e.g., mRNA) polynucleotides comprise a signal peptide. Signal peptides, comprising the N-terminal 15-60 amino acids of proteins, are typically needed for the translocation across the membrane on the secretory pathway and, thus, universally control the entry of most proteins both in eukaryotes and prokaryotes to the secretory pathway. Signal peptides generally include three regions: an N-terminal region of differing length, which usually comprises positively charged amino acids; a hydrophobic region; and a short carboxy-terminal peptide region. In eukaryotes, the signal peptide of a nascent precursor protein (pre-protein) directs the ribosome to the rough endoplasmic reticulum (ER) membrane and initiates the transport of the growing peptide chain across it for processing. ER processing produces mature proteins, wherein the signal peptide is cleaved from precursor proteins, typically by a ER-resident signal peptidase of the host cell, or they remain uncleaved and function as a membrane anchor. A signal peptide may also facilitate the targeting of the protein to the cell membrane. The signal peptide, however, is not responsible for the final destination of the mature protein. Secretory proteins devoid of additional address tags in their sequence are by default secreted to the external environment. During recent years, a more advanced view of signal peptides has evolved, showing that the functions and immunodominance of certain signal peptides are much more versatile than previously anticipated.


Influenza vaccines of the present disclosure may comprise, for example, RNA (e.g., mRNA) polynucleotides encoding an artificial signal peptide, wherein the signal peptide coding sequence is operably linked to and is in frame with the coding sequence of the antigenic polypeptide. Thus, influenza vaccines of the present disclosure, in some embodiments, produce an antigenic polypeptide fused to a signal peptide. In some embodiments, a signal peptide is fused to the N-terminus of the antigenic polypeptide. In some embodiments, a signal peptide is fused to the C-terminus of the antigenic polypeptide.


In some embodiments, the signal peptide fused to the antigenic polypeptide is an artificial signal peptide. In some embodiments, an artificial signal peptide fused to the antigenic polypeptide encoded by the RNA (e.g., mRNA) vaccine is obtained from an immunoglobulin protein, e.g., an IgE signal peptide or an IgG signal peptide. In some embodiments, a signal peptide fused to the antigenic polypeptide encoded by a RNA (e.g., mRNA) vaccine is an Ig heavy chain epsilon-1 signal peptide (IgE HC SP) having the sequence of: MDWTWILFLVAAATRVHS; SEQ ID NO: 481. In some embodiments, a signal peptide fused to the antigenic polypeptide encoded by the (e.g., mRNA) RNA (e.g., mRNA) vaccine is an IgGk chain V-III region HAH signal peptide (IgGk SP) having the sequence of METPAQLLFLLLLWLPDTTG; SEQ ID NO: 480. In some embodiments, the signal peptide is selected from: Japanese encephalitis PRM signal sequence (MLGSNSGQRVVFTILLLLVAPAYS; SEQ ID NO: 482), VSVg protein signal sequence (MKCLLYLAFLFIGVNCA; SEQ ID NO: 483) and Japanese encephalitis JEV signal sequence (MWLVSLAIVTACAGA; SEQ ID NO: 484).


In some embodiments, the antigenic polypeptide encoded by a RNA (e.g., mRNA) vaccine comprises an amino acid sequence identified by any one of SEQ ID NO: 1-444, 458, 460, 462-479, or 543-565 (see also Tables 7-13 and 26) fused to a signal peptide identified by any one of SEQ ID NO: 480-484. The examples disclosed herein are not meant to be limiting and any signal peptide that is known in the art to facilitate targeting of a protein to ER for processing and/or targeting of a protein to the cell membrane may be used in accordance with the present disclosure.


A signal peptide may have a length of 15-60 amino acids. For example, a signal peptide may have a length of 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, or 60 amino acids. In some embodiments, a signal peptide has a length of 20-60, 25-60, 30-60, 35-60, 40-60, 45-60, 50-60, 55-60, 15-55, 20-55, 25-55, 30-55, 35-55, 40-55, 45-55, 50-55, 15-50, 20-50, 25-50, 30-50, 35-50, 40-50, 45-50, 15-45, 20-45, 25-45, 30-45, 35-45, 40-45, 15-40, 20-40, 25-40, 30-40, 35-40, 15-35, 20-35, 25-35, 30-35, 15-30, 20-30, 25-30, 15-25, 20-25, or 15-20 amino acids.


A signal peptide is typically cleaved from the nascent polypeptide at the cleavage junction during ER processing. The mature antigenic polypeptide produce by an influenza RNA (e.g., mRNA) vaccine of the present disclosure typically does not comprise a signal peptide.


Chemical Modifications

Influenza vaccines of the present disclosure, in some embodiments, comprise at least RNA (e.g. mRNA) polynucleotide having an open reading frame encoding at least one antigenic polypeptide that comprises at least one chemical modification.


The terms “chemical modification” and “chemically modified” refer to modification with respect to adenosine (A), guanosine (G), uridine (U), thymidine (T) or cytidine (C) ribonucleosides or deoxyribnucleosides in at least one of their position, pattern, percent or population. Generally, these terms do not refer to the ribonucleotide modifications in naturally occurring 5′-terminal mRNA cap moieties. With respect to a polypeptide, the term “modification” refers to a modification relative to the canonical set 20 amino acids. Polypeptides, as provided herein, are also considered “modified” of they contain amino acid substitutions, insertions or a combination of substitutions and insertions.


Polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides), in some embodiments, comprise various (more than one) different modifications. In some embodiments, a particular region of a polynucleotide contains one, two or more (optionally different) nucleoside or nucleotide modifications. In some embodiments, a modified RNA polynucleotide (e.g., a modified mRNA polynucleotide), introduced to a cell or organism, exhibits reduced degradation in the cell or organism, respectively, relative to an unmodified polynucleotide. In some embodiments, a modified RNA polynucleotide (e.g., a modified mRNA polynucleotide), introduced into a cell or organism, may exhibit reduced immunogenicity in the cell or organism, respectively (e.g., a reduced innate response).


Modifications of polynucleotides include, without limitation, those described herein. Polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) may comprise modifications that are naturally-occurring, non-naturally-occurring or the polynucleotide may comprise a combination of naturally-occurring and non-naturally-occurring modifications. Polynucleotides may include any useful modification, for example, of a sugar, a nucleobase, or an internucleoside linkage (e.g., to a linking phosphate, to a phosphodiester linkage or to the phosphodiester backbone).


Polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides), in some embodiments, comprise non-natural modified nucleotides that are introduced during synthesis or post-synthesis of the polynucleotides to achieve desired functions or properties. The modifications may be present on an internucleotide linkages, purine or pyrimidine bases, or sugars. The modification may be introduced with chemical synthesis or with a polymerase enzyme at the terminal of a chain or anywhere else in the chain. Any of the regions of a polynucleotide may be chemically modified.


The present disclosure provides for modified nucleosides and nucleotides of a polynucleotide (e.g., RNA polynucleotides, such as mRNA polynucleotides). A “nucleoside” refers to a compound containing a sugar molecule (e.g., a pentose or ribose) or a derivative thereof in combination with an organic base (e.g., a purine or pyrimidine) or a derivative thereof (also referred to herein as “nucleobase”). A nucleotide” refers to a nucleoside, including a phosphate group. Modified nucleotides may by synthesized by any useful method, such as, for example, chemically, enzymatically, or recombinantly, to include one or more modified or non-natural nucleosides. Polynucleotides may comprise a region or regions of linked nucleosides. Such regions may have variable backbone linkages. The linkages may be standard phosphodioester linkages, in which case the polynucleotides would comprise regions of nucleotides.


Modified nucleotide base pairing encompasses not only the standard adenosine-thymine, adenosine-uracil, or guanosine-cytosine base pairs, but also base pairs formed between nucleotides and/or modified nucleotides comprising non-standard or modified bases, wherein the arrangement of hydrogen bond donors and hydrogen bond acceptors permits hydrogen bonding between a non-standard base and a standard base or between two complementary non-standard base structures. One example of such non-standard base pairing is the base pairing between the modified nucleotide inosine and adenine, cytosine or uracil. Any combination of base/sugar or linker may be incorporated into polynucleotides of the present disclosure.


Modifications of polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) that are useful in the vaccines of the present disclosure include, but are not limited to the following: 2-methylthio-N6-(cis-hydroxyisopentenyl)adenosine; 2-methylthio-N6-methyladenosine; 2-methylthio-N6-threonyl carbamoyladenosine; N6-glycinylcarbamoyladenosine; N6-isopentenyladenosine; N6-methyladenosine; N6-threonylcarbamoyladenosine; 1,2′-O-dimethyladenosine; 1-methyladenosine; 2′-O-methyladenosine; 2′-O-ribosyladenosine (phosphate); 2-methyladenosine; 2-methylthio-N6 isopentenyladenosine; 2-methylthio-N6-hydroxynorvalyl carbamoyladenosine; 2′-O-methyladenosine; 2′-O-ribosyladenosine (phosphate); Isopentenyladenosine; N6-(cis-hydroxyisopentenyl)adenosine; N6,2′-O-dimethyladenosine; N6,2′-O-dimethyladenosine; N6,N6,2′-O-trimethyladenosine; N6,N6-dimethyladenosine; N6-acetyladenosine; N6-hydroxynorvalylcarbamoyladenosine; N6-methyl-N6-threonylcarbamoyladenosine; 2-methyladenosine; 2-methylthio-N6-isopentenyladenosine; 7-deaza-adenosine; N1-methyl-adenosine; N6, N6 (dimethyl)adenine; N6-cis-hydroxy-isopentenyl-adenosine; α-thio-adenosine; 2 (amino)adenine; 2 (aminopropyl)adenine; 2 (methylthio) N6 (isopentenyl)adenine; 2-(alkyl)adenine; 2-(aminoalkyl)adenine; 2-(aminopropyl)adenine; 2-(halo)adenine; 2-(halo)adenine; 2-(propyl)adenine; 2′-Amino-2′-deoxy-ATP; 2′-Azido-2′-deoxy-ATP; 2′-Deoxy-2′-a-aminoadenosine TP; 2′-Deoxy-2′-a-azidoadenosine TP; 6 (alkyl)adenine; 6 (methyl)adenine; 6-(alkyl)adenine; 6-(methyl)adenine; 7 (deaza)adenine; 8 (alkenyl)adenine; 8 (alkynyl)adenine; 8 (amino)adenine; 8 (thioalkyl)adenine; 8-(alkenyl)adenine; 8-(alkyl)adenine; 8-(alkynyl)adenine; 8-(amino)adenine; 8-(halo)adenine; 8-(hydroxyl)adenine; 8-(thioalkyl)adenine; 8-(thiol)adenine; 8-azido-adenosine; aza adenine; deaza adenine; N6 (methyl)adenine; N6-(isopentyl)adenine; 7-deaza-8-aza-adenosine; 7-methyladenine; 1-Deazaadenosine TP; 2′ Fluoro-N6-Bz-deoxyadenosine TP; 2′-OMe-2-Amino-ATP; 2′O-methyl-N6-Bz-deoxyadenosine TP; 2′-a-Ethynyladenosine TP; 2-aminoadenine; 2-Aminoadenosine TP; 2-Amino-ATP; 2′-a-Trifluoromethyladenosine TP; 2-Azidoadenosine TP; 2′-b-Ethynyladenosine TP; 2-Bromoadenosine TP; 2′-b-Trifluoromethyladenosine TP; 2-Chloroadenosine TP; 2′-Deoxy-2′,2′-difluoroadenosine TP; 2′-Deoxy-2′-a-mercaptoadenosine TP; 2′-Deoxy-2′-a-thiomethoxyadenosine TP; 2′-Deoxy-2′-b-aminoadenosine TP; 2′-Deoxy-2′-b-azidoadenosine TP; 2′-Deoxy-2′-b-bromoadenosine TP; 2′-Deoxy-2′-b-chloroadenosine TP; 2′-Deoxy-2′-b-fluoroadenosine TP; 2′-Deoxy-2′-b-iodoadenosine TP; 2′-Deoxy-2′-b-mercaptoadenosine TP; 2′-Deoxy-2′-b-thiomethoxyadenosine TP; 2-Fluoroadenosine TP; 2-Iodoadenosine TP; 2-Mercaptoadenosine TP; 2-methoxy-adenine; 2-methylthio-adenine; 2-Trifluoromethyladenosine TP; 3-Deaza-3-bromoadenosine TP; 3-Deaza-3-chloroadenosine TP; 3-Deaza-3-fluoroadenosine TP; 3-Deaza-3-iodoadenosine TP; 3-Deazaadenosine TP; 4′-Azidoadenosine TP; 4′-Carbocyclic adenosine TP; 4′-Ethynyladenosine TP; 5′-Homo-adenosine TP; 8-Aza-ATP; 8-bromo-adenosine TP; 8-Trifluoromethyladenosine TP; 9-Deazaadenosine TP; 2-aminopurine; 7-deaza-2,6-diaminopurine; 7-deaza-8-aza-2,6-diaminopurine; 7-deaza-8-aza-2-aminopurine; 2,6-diaminopurine; 7-deaza-8-aza-adenine, 7-deaza-2-aminopurine; 2-thiocytidine; 3-methylcytidine; 5-formylcytidine; 5-hydroxymethylcytidine; 5-methylcytidine; N4-acetylcytidine; 2′-O-methylcytidine; 2′-O-methylcytidine; 5,2′-O-dimethylcytidine; 5-formyl-2′-O-methylcytidine; Lysidine; N4,2′-O-dimethylcytidine; N4-acetyl-2′-O-methylcytidine; N4-methylcytidine; N4,N4-Dimethyl-2′-OMe-Cytidine TP; 4-methylcytidine; 5-aza-cytidine; Pseudo-iso-cytidine; pyrrolo-cytidine; α-thio-cytidine; 2-(thio)cytosine; 2′-Amino-2′-deoxy-CTP; 2′-Azido-2′-deoxy-CTP; 2′-Deoxy-2′-a-aminocytidine TP; 2′-Deoxy-2′-a-azidocytidine TP; 3 (deaza) 5 (aza)cytosine; 3 (methyl)cytosine; 3-(alkyl)cytosine; 3-(deaza) 5 (aza)cytosine; 3-(methyl)cytidine; 4,2′-O-dimethylcytidine; 5 (halo)cytosine; 5 (methyl)cytosine; 5 (propynyl)cytosine; 5 (trifluoromethyl)cytosine; 5-(alkyl)cytosine; 5-(alkynyl)cytosine; 5-(halo)cytosine; 5-(propynyl)cytosine; 5-(trifluoromethyl)cytosine; 5-bromo-cytidine; 5-iodo-cytidine; 5-propynyl cytosine; 6-(azo)cytosine; 6-aza-cytidine; aza cytosine; deaza cytosine; N4 (acetyl)cytosine; 1-methyl-1-deaza-pseudoisocytidine; 1-methyl-pseudoisocytidine; 2-methoxy-5-methyl-cytidine; 2-methoxy-cytidine; 2-thio-5-methyl-cytidine; 4-methoxy-1-methyl-pseudoisocytidine; 4-methoxy-pseudoisocytidine; 4-thio-1-methyl-1-deaza-pseudoisocytidine; 4-thio-1-methyl-pseudoisocytidine; 4-thio-pseudoisocytidine; 5-aza-zebularine; 5-methyl-zebularine; pyrrolo-pseudoisocytidine; Zebularine; (E)-5-(2-Bromo-vinyl)cytidine TP; 2,2′-anhydro-cytidine TP hydrochloride; 2′ Fluor-N4-Bz-cytidine TP; 2′ Fluoro-N4-Acetyl-cytidine TP; 2′-O-Methyl-N4-Acetyl-cytidine TP; 2′O-methyl-N4-Bz-cytidine TP; 2′-a-Ethynylcytidine TP; 2′-a-Trifluoromethylcytidine TP; 2′-b-Ethynylcytidine TP; 2′-b-Trifluoromethylcytidine TP; 2′-Deoxy-2′,2′-difluorocytidine TP; 2′-Deoxy-2′-a-mercaptocytidine TP; 2′-Deoxy-2′-a-thiomethoxycytidine TP; 2′-Deoxy-2′-b-aminocytidine TP; 2′-Deoxy-2′-b-azidocytidine TP; 2′-Deoxy-2′-b-bromocytidine TP; 2′-Deoxy-2′-b-chlorocytidine TP; 2′-Deoxy-2′-b-fluorocytidine TP; 2′-Deoxy-2′-b-iodocytidine TP; 2′-Deoxy-2′-b-mercaptocytidine TP; 2′-Deoxy-2′-b-thiomethoxycytidine TP; 2′-O-Methyl-5-(1-propynyl)cytidine TP; 3′-Ethynylcytidine TP; 4′-Azidocytidine TP; 4′-Carbocyclic cytidine TP; 4′-Ethynylcytidine TP; 5-(1-Propynyl)ara-cytidine TP; 5-(2-Chloro-phenyl)-2-thiocytidine TP; 5-(4-Amino-phenyl)-2-thiocytidine TP; 5-Aminoallyl-CTP; 5-Cyanocytidine TP; 5-Ethynylara-cytidine TP; 5-Ethynylcytidine TP; 5′-Homo-cytidine TP; 5-Methoxycytidine TP; 5-Trifluoromethyl-Cytidine TP; N4-Amino-cytidine TP; N4-Benzoyl-cytidine TP; Pseudoisocytidine; 7-methylguanosine; N2,2′-O-dimethylguanosine; N2-methylguanosine; Wyosine; 1,2′-O-dimethylguanosine; 1-methylguanosine; 2′-O-methylguanosine; 2′-O-ribosylguanosine (phosphate); 2′-O-methylguanosine; 2′-O-ribosylguanosine (phosphate); 7-aminomethyl-7-deazaguanosine; 7-cyano-7-deazaguanosine; Archaeosine; Methylwyosine; N2,7-dimethylguanosine; N2,N2,2′-O-trimethylguanosine; N2,N2,7-trimethylguanosine; N2,N2-dimethylguanosine; N2,7,2′-O-trimethylguanosine; 6-thio-guanosine; 7-deaza-guanosine; 8-oxo-guanosine; N1-methyl-guanosine; α-thio-guanosine; 2 (propyl)guanine; 2-(alkyl)guanine; 2′-Amino-2′-deoxy-GTP; 2′-Azido-2′-deoxy-GTP; 2′-Deoxy-2′-a-aminoguanosine TP; 2′-Deoxy-2′-a-azidoguanosine TP; 6 (methyl)guanine; 6-(alkyl)guanine; 6-(methyl)guanine; 6-methyl-guanosine; 7 (alkyl)guanine; 7 (deaza)guanine; 7 (methyl)guanine; 7-(alkyl)guanine; 7-(deaza)guanine; 7-(methyl)guanine; 8 (alkyl)guanine; 8 (alkynyl)guanine; 8 (halo)guanine; 8 (thioalkyl)guanine; 8-(alkenyl)guanine; 8-(alkyl)guanine; 8-(alkynyl)guanine; 8-(amino)guanine; 8-(halo)guanine; 8-(hydroxyl)guanine; 8-(thioalkyl)guanine; 8-(thiol)guanine; aza guanine; deaza guanine; N (methyl)guanine; N-(methyl)guanine; 1-methyl-6-thio-guanosine; 6-methoxy-guanosine; 6-thio-7-deaza-8-aza-guanosine; 6-thio-7-deaza-guanosine; 6-thio-7-methyl-guanosine; 7-deaza-8-aza-guanosine; 7-methyl-8-oxo-guanosine; N2,N2-dimethyl-6-thio-guanosine; N2-methyl-6-thio-guanosine; 1-Me-GTP; 2′ Fluoro-N2-isobutyl-guanosine TP; 2′O-methyl-N2-isobutyl-guanosine TP; 2′-a-Ethynylguanosine TP; 2′-a-Trifluoromethylguanosine TP; 2′-b-Ethynylguanosine TP; 2′-b-Trifluoromethylguanosine TP; 2′-Deoxy-2′,2′-difluoroguanosine TP; 2′-Deoxy-2′-a-mercaptoguanosine TP; 2′-Deoxy-2′-a-thiomethoxyguanosine TP; 2′-Deoxy-2′-b-aminoguanosine TP; 2′-Deoxy-2′-b-azidoguanosine TP; 2′-Deoxy-2′-b-bromoguanosine TP; 2′-Deoxy-2′-b-chloroguanosine TP; 2′-Deoxy-2′-b-fluoroguanosine TP; 2′-Deoxy-2′-b-iodoguanosine TP; 2′-Deoxy-2′-b-mercaptoguanosine TP; 2′-Deoxy-2′-b-thiomethoxyguanosine TP; 4′-Azidoguanosine TP; 4′-Carbocyclic guanosine TP; 4′-Ethynylguanosine TP; 5′-Homo-guanosine TP; 8-bromo-guanosine TP; 9-Deazaguanosine TP; N2-isobutyl-guanosine TP; 1-methylinosine; Inosine; 1,2′-O-dimethylinosine; 2′-O-methylinosine; 7-methylinosine; 2′-O-methylinosine; Epoxyqueuosine; galactosyl-queuosine; Mannosylqueuosine; Queuosine; allyamino-thymidine; aza thymidine; deaza thymidine; deoxy-thymidine; 2′-O-methyluridine; 2-thiouridine; 3-methyluridine; 5-carboxymethyluridine; 5-hydroxyuridine; 5-methyluridine; 5-taurinomethyl-2-thiouridine; 5-taurinomethyluridine; Dihydrouridine; Pseudouridine; (3-(3-amino-3-carboxypropyl)uridine; 1-methyl-3-(3-amino-5-carboxypropyl)pseudouridine; 1-methylpseduouridine; 1-methyl-pseudouridine; 2′-O-methyluridine; 2′-O-methylpseudouridine; 2′-O-methyluridine; 2-thio-2′-O-methyluridine; 3-(3-amino-3-carboxypropyl)uridine; 3,2′-O-dimethyluridine; 3-Methyl-pseudo-Uridine TP; 4-thiouridine; 5-(carboxyhydroxymethyl)uridine; 5-(carboxyhydroxymethyl)uridine methyl ester; 5,2′-O-dimethyluridine; 5,6-dihydro-uridine; 5-aminomethyl-2-thiouridine; 5-carbamoylmethyl-2′-O-methyluridine; 5-carbamoylmethyluridine; 5-carboxyhydroxymethyluridine; 5-carboxyhydroxymethyluridine methyl ester; 5-carboxymethylaminomethyl-2′-O-methyluridine; 5-carboxymethylaminomethyl-2-thiouridine; 5-carboxymethylaminomethyl-2-thiouridine; 5-carboxymethylaminomethyluridine; 5-carboxymethylaminomethyluridine; 5-Carbamoylmethyluridine TP; 5-methoxycarbonylmethyl-2′-O-methyluridine; 5-methoxycarbonylmethyl-2-thiouridine; 5-methoxycarbonylmethyluridine; 5-methoxyuridine; 5-methyl-2-thiouridine; 5-methylaminomethyl-2-selenouridine; 5-methylaminomethyl-2-thiouridine; 5-methylaminomethyluridine; 5-Methyldihydrouridine; 5-Oxyacetic acid-Uridine TP; 5-Oxyacetic acid-methyl ester-Uridine TP; N1-methyl-pseudo-uridine; uridine 5-oxyacetic acid; uridine 5-oxyacetic acid methyl ester; 3-(3-Amino-3-carboxypropyl)-Uridine TP; 5-(iso-Pentenylaminomethyl)-2-thiouridine TP; 5-(iso-Pentenylaminomethyl)-2′-O-methyluridine TP; 5-(iso-Pentenylaminomethyl)uridine TP; 5-propynyl uracil; α-thio-uridine; 1 (aminoalkylamino-carbonylethylenyl)-2(thio)-pseudouracil; 1 (aminoalkylaminocarbonylethylenyl)-2,4-(dithio)pseudouracil; 1 (aminoalkylaminocarbonylethylenyl)-4 (thio)pseudouracil; 1 (aminoalkylaminocarbonylethylenyl)-pseudouracil; 1 (aminocarbonylethylenyl)-2(thio)-pseudouracil; 1 (aminocarbonylethylenyl)-2,4-(dithio)pseudouracil; 1 (aminocarbonylethylenyl)-4 (thio)pseudouracil; 1 (aminocarbonylethylenyl)-pseudouracil; 1 substituted 2(thio)-pseudouracil; 1 substituted 2,4-(dithio)pseudouracil; 1 substituted 4 (thio)pseudouracil; 1 substituted pseudouracil; 1-(aminoalkylamino-carbonylethylenyl)-2-(thio)-pseudouracil; 1-Methyl-3-(3-amino-3-carboxypropyl) pseudouridine TP; 1-Methyl-3-(3-amino-3-carboxypropyl)pseudo-UTP; 1-Methyl-pseudo-UTP; 2 (thio)pseudouracil; 2′ deoxy uridine; 2′ fluorouridine; 2-(thio)uracil; 2,4-(dithio)psuedouracil; 2′ methyl, 2′ amino, 2′ azido, 2′ fluro-guanosine; 2′-Amino-2′-deoxy-UTP; 2′-Azido-2′-deoxy-UTP; 2′-Azido-deoxyuridine TP; 2′-O-methylpseudouridine; 2′ deoxy uridine; 2′ fluorouridine; 2′-Deoxy-2′-a-aminouridine TP; 2′-Deoxy-2′-a-azidouridine TP; 2-methylpseudouridine; 3 (3 amino-3 carboxypropyl)uracil; 4 (thio)pseudouracil; 4-(thio)pseudouracil; 4-(thio)uracil; 4-thiouracil; 5 (1,3-diazole-1-alkyl)uracil; 5 (2-aminopropyl)uracil; 5 (aminoalkyl)uracil; 5 (dimethylaminoalkyl)uracil; 5 (guanidiniumalkyl)uracil; 5 (methoxycarbonylmethyl)-2-(thio)uracil; 5 (methoxycarbonyl-methyl)uracil; 5 (methyl) 2 (thio)uracil; 5 (methyl) 2,4 (dithio)uracil; 5 (methyl) 4 (thio)uracil; 5 (methylaminomethyl)-2 (thio)uracil; 5 (methylaminomethyl)-2,4 (dithio)uracil; 5 (methylaminomethyl)-4 (thio)uracil; 5 (propynyl)uracil; 5 (trifluoromethyl)uracil; 5-(2-aminopropyl)uracil; 5-(alkyl)-2-(thio)pseudouracil; 5-(alkyl)-2,4 (dithio)pseudouracil; 5-(alkyl)-4 (thio)pseudouracil; 5-(alkyl)pseudouracil; 5-(alkyl)uracil; 5-(alkynyl)uracil; 5-(allylamino)uracil; 5-(cyanoalkyl)uracil; 5-(dialkylaminoalkyl)uracil; 5-(dimethylaminoalkyl)uracil; 5-(guanidiniumalkyl)uracil; 5-(halo)uracil; 5-(1,3-diazole-1-alkyl)uracil; 5-(methoxy)uracil; 5-(methoxycarbonylmethyl)-2-(thio)uracil; 5-(methoxycarbonyl-methyl)uracil; 5-(methyl) 2(thio)uracil; 5-(methyl) 2,4 (dithio)uracil; 5-(methyl) 4 (thio)uracil; 5-(methyl)-2-(thio)pseudouracil; 5-(methyl)-2,4 (dithio)pseudouracil; 5-(methyl)-4 (thio)pseudouracil; 5-(methyl)pseudouracil; 5-(methylaminomethyl)-2 (thio)uracil; 5-(methylaminomethyl)-2,4(dithio)uracil; 5-(methylaminomethyl)-4-(thio)uracil; 5-(propynyl)uracil; 5-(trifluoromethyl)uracil; 5-aminoallyl-uridine; 5-bromo-uridine; 5-iodo-uridine; 5-uracil; 6 (azo)uracil; 6-(azo)uracil; 6-aza-uridine; allyamino-uracil; aza uracil; deaza uracil; N3 (methyl)uracil; P seudo-UTP-1-2-ethanoic acid; Pseudouracil; 4-Thio-pseudo-UTP; 1-carboxymethyl-pseudouridine; 1-methyl-1-deaza-pseudouridine; 1-propynyl-uridine; 1-taurinomethyl-1-methyl-uridine; 1-taurinomethyl-4-thio-uridine; 1-taurinomethyl-pseudouridine; 2-methoxy-4-thio-pseudouridine; 2-thio-1-methyl-1-deaza-pseudouridine; 2-thio-1-methyl-pseudouridine; 2-thio-5-aza-uridine; 2-thio-dihydropseudouridine; 2-thio-dihydrouridine; 2-thio-pseudouridine; 4-methoxy-2-thio-pseudouridine; 4-methoxy-pseudouridine; 4-thio-1-methyl-pseudouridine; 4-thio-pseudouridine; 5-aza-uridine; Dihydropseudouridine; (±)1-(2-Hydroxypropyl)pseudouridine TP; (2R)-1-(2-Hydroxypropyl)pseudouridine TP; (2S)-1-(2-Hydroxypropyl)pseudouridine TP; (E)-5-(2-Bromo-vinyl)ara-uridine TP; (E)-5-(2-Bromo-vinyl)uridine TP; (Z)-5-(2-Bromo-vinyl)ara-uridine TP; (Z)-5-(2-Bromo-vinyl)uridine TP; 1-(2,2,2-Trifluoroethyl)-pseudo-UTP; 1-(2,2,3,3,3-Pentafluoropropyl)pseudouridine TP; 1-(2,2-Diethoxyethyl)pseudouridine TP; 1-(2,4,6-Trimethylbenzyl)pseudouridine TP; 1-(2,4,6-Trimethyl-benzyl)pseudo-UTP; 1-(2,4,6-Trimethyl-phenyl)pseudo-UTP; 1-(2-Amino-2-carboxyethyl)pseudo-UTP; 1-(2-Amino-ethyl)pseudo-UTP; 1-(2-Hydroxyethyl)pseudouridine TP; 1-(2-Methoxyethyl)pseudouridine TP; 1-(3,4-Bis-trifluoromethoxybenzyl)pseudouridine TP; 1-(3,4-Dimethoxybenzyl)pseudouridine TP; 1-(3-Amino-3-carboxypropyl)pseudo-UTP; 1-(3-Amino-propyl)pseudo-UTP; 1-(3-Cyclopropyl-prop-2-ynyl)pseudouridine TP; 1-(4-Amino-4-carboxybutyl)pseudo-UTP; 1-(4-Amino-benzyl)pseudo-UTP; 1-(4-Amino-butyl)pseudo-UTP; 1-(4-Amino-phenyl)pseudo-UTP; 1-(4-Azidobenzyl)pseudouridine TP; 1-(4-Bromobenzyl)pseudouridine TP; 1-(4-Chlorobenzyl)pseudouridine TP; 1-(4-Fluorobenzyl)pseudouridine TP; 1-(4-Iodobenzyl)pseudouridine TP; 1-(4-Methanesulfonylbenzyl)pseudouridine TP; 1-(4-Methoxybenzyl)pseudouridine TP; 1-(4-Methoxy-benzyl)pseudo-UTP; 1-(4-Methoxy-phenyl)pseudo-UTP; 1-(4-Methylbenzyl)pseudouridine TP; 1-(4-Methyl-benzyl)pseudo-UTP; 1-(4-Nitrobenzyl)pseudouridine TP; 1-(4-Nitro-benzyl)pseudo-UTP; 1(4-Nitro-phenyl)pseudo-UTP; 1-(4-Thiomethoxybenzyl)pseudouridine TP; 1-(4-Trifluoromethoxybenzyl)pseudouridine TP; 1-(4-Trifluoromethylbenzyl)pseudouridine TP; 1-(5-Amino-pentyl)pseudo-UTP; 1-(6-Amino-hexyl)pseudo-UTP; 1,6-Dimethyl-pseudo-UTP; 1-[3-(2-{2-[2-(2-Aminoethoxy)-ethoxy]-ethoxy}-ethoxy)-propionyl]pseudouridine TP; 1-13-[2-(2-Aminoethoxy)-ethoxy]-propionyl} pseudouridine TP; 1-Acetylpseudouridine TP; 1-Alkyl-6-(1-propynyl)-pseudo-UTP; 1-Alkyl-6-(2-propynyl)-pseudo-UTP; 1-Alkyl-6-allyl-pseudo-UTP; 1-Alkyl-6-ethynyl-pseudo-UTP; 1-Alkyl-6-homoallyl-pseudo-UTP; 1-Alkyl-6-vinyl-pseudo-UTP; 1-Allylpseudouridine TP; 1-Aminomethyl-pseudo-UTP; 1-Benzoylpseudouridine TP; 1-Benzyloxymethylpseudouridine TP; 1-Benzyl-pseudo-UTP; 1-Biotinyl-PEG2-pseudouridine TP; 1-Biotinylpseudouridine TP; 1-Butyl-pseudo-UTP; 1-Cyanomethylpseudouridine TP; 1-Cyclobutylmethyl-pseudo-UTP; 1-Cyclobutyl-pseudo-UTP; 1-Cycloheptylmethyl-pseudo-UTP; 1-Cycloheptyl-pseudo-UTP; 1-Cyclohexylmethyl-pseudo-UTP; 1-Cyclohexyl-pseudo-UTP; 1-Cyclooctylmethyl-pseudo-UTP; 1-Cyclooctyl-pseudo-UTP; 1-Cyclopentylmethyl-pseudo-UTP; 1-Cyclopentyl-pseudo-UTP; 1-Cyclopropylmethyl-pseudo-UTP; 1-Cyclopropyl-pseudo-UTP; 1-Ethyl-pseudo-UTP; 1-Hexyl-pseudo-UTP; 1-Homoallylpseudouridine TP; 1-Hydroxymethylpseudouridine TP; 1-iso-propyl-pseudo-UTP; 1-Me-2-thio-pseudo-UTP; 1-Me-4-thio-pseudo-UTP; 1-Me-alpha-thio-pseudo-UTP; 1-Methanesulfonylmethylpseudouridine TP; 1-Methoxymethylpseudouridine TP; 1-Methyl-6-(2,2,2-Trifluoroethyl)pseudo-UTP; 1-Methyl-6-(4-morpholino)-pseudo-UTP; 1-Methyl-6-(4-thiomorpholino)-pseudo-UTP; 1-Methyl-6-(substituted phenyl)pseudo-UTP; 1-Methyl-6-amino-pseudo-UTP; 1-Methyl-6-azido-pseudo-UTP; 1-Methyl-6-bromo-pseudo-UTP; 1-Methyl-6-butyl-pseudo-UTP; 1-Methyl-6-chloro-pseudo-UTP; 1-Methyl-6-cyano-pseudo-UTP; 1-Methyl-6-dimethylamino-pseudo-UTP; 1-Methyl-6-ethoxy-pseudo-UTP; 1-Methyl-6-ethylcarboxylate-pseudo-UTP; 1-Methyl-6-ethyl-pseudo-UTP; 1-Methyl-6-fluoro-pseudo-UTP; 1-Methyl-6-formyl-pseudo-UTP; 1-Methyl-6-hydroxyamino-pseudo-UTP; 1-Methyl-6-hydroxy-pseudo-UTP; 1-Methyl-6-iodo-pseudo-UTP; 1-Methyl-6-iso-propyl-pseudo-UTP; 1-Methyl-6-methoxy-pseudo-UTP; 1-Methyl-6-methylamino-pseudo-UTP; 1-Methyl-6-phenyl-pseudo-UTP; 1-Methyl-6-propyl-pseudo-UTP; 1-Methyl-6-tert-butyl-pseudo-UTP; 1-Methyl-6-trifluoromethoxy-pseudo-UTP; 1-Methyl-6-trifluoromethyl-pseudo-UTP; 1-Morpholinomethylpseudouridine TP; 1-Pentyl-pseudo-UTP; 1-Phenyl-pseudo-UTP; 1-Pivaloylpseudouridine TP; 1-Propargylpseudouridine TP; 1-Propyl-pseudo-UTP; 1-propynyl-pseudouridine; 1-p-tolyl-pseudo-UTP; 1-tert-Butyl-pseudo-UTP; 1-Thiomethoxymethylpseudouridine TP; 1-Thiomorpholinomethylpseudouridine TP; 1-Trifluoroacetylpseudouridine TP; 1-Trifluoromethyl-pseudo-UTP; 1-Vinylpseudouridine TP; 2,2′-anhydro-uridine TP; 2′-bromo-deoxyuridine TP; 2′-F-5-Methyl-2′-deoxy-UTP; 2′-OMe-5-Me-UTP; 2′-OMe-pseudo-UTP; 2′-a-Ethynyluridine TP; 2′-a-Trifluoromethyluridine TP; 2′-b-Ethynyluridine TP; 2′-b-Trifluoromethyluridine TP; 2′-Deoxy-2′,2′-difluorouridine TP; 2′-Deoxy-2′-a-mercaptouridine TP; 2′-Deoxy-2′-a-thiomethoxyuridine TP; 2′-Deoxy-2′-b-aminouridine TP; 2′-Deoxy-2′-b-azidouridine TP; 2′-Deoxy-2′-b-bromouridine TP; 2′-Deoxy-2′-b-chlorouridine TP; 2′-Deoxy-2′-b-fluorouridine TP; 2′-Deoxy-2′-b-iodouridine TP; 2′-Deoxy-2′-b-mercaptouridine TP; 2′-Deoxy-2′-b-thiomethoxyuridine TP; 2-methoxy-4-thio-uridine; 2-methoxyuridine; 2′-O-Methyl-5-(1-propynyl)uridine TP; 3-Alkyl-pseudo-UTP; 4′-Azidouridine TP; 4′-Carbocyclic uridine TP; 4′-Ethynyluridine TP; 5-(1-Propynyl)ara-uridine TP; 5-(2-Furanyl)uridine TP; 5-Cyanouridine TP; 5-Dimethylaminouridine TP; 5′-Homo-uridine TP; 5-iodo-2′-fluoro-deoxyuridine TP; 5-Phenylethynyluridine TP; 5-Trideuteromethyl-6-deuterouridine TP; 5-Trifluoromethyl-Uridine TP; 5-Vinylarauridine TP; 6-(2,2,2-Trifluoroethyl)-pseudo-UTP; 6-(4-Morpholino)-pseudo-UTP; 6-(4-Thiomorpholino)-pseudo-UTP; 6-(Substituted-Phenyl)-pseudo-UTP; 6-Amino-pseudo-UTP; 6-Azido-pseudo-UTP; 6-Bromo-pseudo-UTP; 6-Butyl-pseudo-UTP; 6-Chloro-pseudo-UTP; 6-Cyano-pseudo-UTP; 6-Dimethylamino-pseudo-UTP; 6-Ethoxy-pseudo-UTP; 6-Ethylcarboxylate-pseudo-UTP; 6-Ethyl-pseudo-UTP; 6-Fluoro-pseudo-UTP; 6-Formyl-pseudo-UTP; 6-Hydroxyamino-pseudo-UTP; 6-Hydroxy-pseudo-UTP; 6-Iodo-pseudo-UTP; 6-iso-Propyl-pseudo-UTP; 6-Methoxy-pseudo-UTP; 6-Methylamino-pseudo-UTP; 6-Methyl-pseudo-UTP; 6-Phenyl-pseudo-UTP; 6-Phenyl-pseudo-UTP; 6-Propyl-pseudo-UTP; 6-tert-Butyl-pseudo-UTP; 6-Trifluoromethoxy-pseudo-UTP; 6-Trifluoromethyl-pseudo-UTP; Alpha-thio-pseudo-UTP; Pseudouridine 1-(4-methylbenzenesulfonic acid) TP; Pseudouridine 1-(4-methylbenzoic acid) TP; Pseudouridine TP 1-[3-(2-ethoxy)]propionic acid; Pseudouridine TP 1-[3-{2-(2-[2-(2-ethoxy)-ethoxy]-ethoxy)-ethoxy}]propionic acid; Pseudouridine TP 1-[3-{2-(2-[2-{2(2-ethoxy)-ethoxy}-ethoxy]-ethoxy)-ethoxy}]propionic acid; Pseudouridine TP 1-[3-{2-(2-[2-ethoxy]-ethoxy)-ethoxy}]propionic acid; Pseudouridine TP 1-[3-{2-(2-ethoxy)-ethoxy}] propionic acid; Pseudouridine TP 1-methylphosphonic acid; Pseudouridine TP 1-methylphosphonic acid diethyl ester; Pseudo-UTP-N1-3-propionic acid; Pseudo-UTP-N1-4-butanoic acid; Pseudo-UTP-N1-5-pentanoic acid; Pseudo-UTP-N1-6-hexanoic acid; Pseudo-UTP-N1-7-heptanoic acid; Pseudo-UTP-N1-methyl-p-benzoic acid; Pseudo-UTP-N1-p-benzoic acid; Wybutosine; Hydroxywybutosine; Isowyosine; Peroxywybutosine; undermodified hydroxywybutosine; 4-demethylwyosine; 2,6-(diamino)purine; 1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl: 1,3-(diaza)-2-(oxo)-phenthiazin-1-yl; 1,3-(diaza)-2-(oxo)-phenoxazin-1-yl; 1,3,5-(triaza)-2,6-(dioxa)-naphthalene; 2 (amino)purine; 2,4,5-(trimethyl)phenyl; 2′ methyl, 2′ amino, 2′ azido, 2′ fluro-cytidine; 2′ methyl, 2′ amino, 2′ azido, 2′ fluro-adenine; 2′ methyl, 2′ amino, 2′ azido, 2′ fluro-uridine; 2′-amino-2′-deoxyribose; 2-amino-6-Chloro-purine; 2-aza-inosinyl; 2′-azido-2′-deoxyribose; 2′ fluoro-2′-deoxyribose; 2′-fluoro-modified bases; 2′-O-methyl-ribose; 2-oxo-7-aminopyridopyrimidin-3-yl; 2-oxo-pyridopyrimidine-3-yl; 2-pyridinone; 3 nitropyrrole; 3-(methyl)-7-(propynyl)isocarbostyrilyl; 3-(methyl)isocarbostyrilyl; 4-(fluoro)-6-(methyl)benzimidazole; 4-(methyl)benzimidazole; 4-(methyl)indolyl; 4,6-(dimethyl)indolyl; 5 nitroindole; 5 substituted pyrimidines; 5-(methyl)isocarbostyrilyl; 5-nitroindole; 6-(aza)pyrimidine; 6-(azo)thymine; 6-(methyl)-7-(aza)indolyl; 6-chloro-purine; 6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; 7-(aminoalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenthiazin-1-yl; 7-(aminoalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl; 7-(aminoalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl; 7-(aminoalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenthiazin-1-yl; 7-(aminoalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl; 7-(aza)indolyl; 7-(guanidiniumalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenoxazinl-yl; 7-(guanidiniumalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenthiazin-1-yl; 7-(guanidiniumalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl; 7-(guanidiniumalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl; 7-(guanidiniumalkyl-hydroxy)-1,3-(diaza)-2-(oxo)-phenthiazin-1-yl; 7-(guanidiniumalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl; 7-(propynyl)isocarbostyrilyl; 7-(propynyl)isocarbostyrilyl, propynyl-7-(aza)indolyl; 7-deaza-inosinyl; 7-substituted 1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl; 7-substituted 1,3-(diaza)-2-(oxo)-phenoxazin-1-yl; 9-(methyl)-imidizopyridinyl; Aminoindolyl; Anthracenyl; bis-ortho-(aminoalkylhydroxy)-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; bis-ortho-substituted-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; Difluorotolyl; Hypoxanthine; Imidizopyridinyl; Inosinyl; Isocarbostyrilyl; Isoguanisine; N2-substituted purines; N6-methyl-2-amino-purine; N6-substituted purines; N-alkylated derivative; Napthalenyl; Nitrobenzimidazolyl; Nitroimidazolyl; Nitroindazolyl; Nitropyrazolyl; Nubularine; 06-substituted purines; O-alkylated derivative; ortho-(aminoalkylhydroxy)-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; ortho-substituted-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; Oxoformycin TP; para-(aminoalkylhydroxy)-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; para-substituted-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; Pentacenyl; Phenanthracenyl; Phenyl; propynyl-7-(aza)indolyl; Pyrenyl; pyridopyrimidin-3-yl; pyridopyrimidin-3-yl, 2-oxo-7-amino-pyridopyrimidin-3-yl; pyrrolo-pyrimidin-2-on-3-yl; Pyrrolopyrimidinyl; Pyrrolopyrizinyl; Stilbenzyl; substituted 1,2,4-triazoles; Tetracenyl; Tubercidine; Xanthine; Xanthosine-5′-TP; 2-thio-zebularine; 5-aza-2-thio-zebularine; 7-deaza-2-amino-purine; pyridin-4-one ribonucleoside; 2-Amino-riboside-TP; Formycin A TP; Formycin B TP; Pyrrolosine TP; 2′-OH-ara-adenosine TP; 2′-OH-ara-cytidine TP; 2′-OH-ara-uridine TP; 2′-OH-ara-guanosine TP; 5-(2-carbomethoxyvinyl)uridine TP; and N6-(19-Amino-pentaoxanonadecyl)adenosine TP.


In some embodiments, polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) include a combination of at least two (e.g., 2, 3, 4 or more) of the aforementioned modified nucleobases.


In some embodiments, modified nucleobases in polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) are selected from the group consisting of pseudouridine (ψ), N1-methylpseudouridine (m1ψ), 2-thiouridine, N1-ethylpseudouridine, 4′-thiouridine, 5-methylcytosine, 2-thio-1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine, 2-thio-dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine, 4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine, 4-thio-pseudouridine, 5-aza-uridine, dihydropseudouridine, 5-methoxyuridine and 2′-O-methyl uridine. In some embodiments, polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) include a combination of at least two (e.g., 2, 3, 4 or more) of the aforementioned modified nucleobases.


In some embodiments, modified nucleobases in polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) are selected from the group consisting of 1-methyl-pseudouridine (m1ψ), 5-methoxy-uridine (mo5U), 5-methyl-cytidine (m5C), pseudouridine (ψ), α-thio-guanosine and α-thio-adenosine. In some embodiments, polynucleotides includes a combination of at least two (e.g., 2, 3, 4 or more) of the aforementioned modified nucleobases.


In some embodiments, polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) comprise pseudouridine (ψ) and 5-methyl-cytidine (m5C). In some embodiments, polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) comprise 1-methyl-pseudouridine (m1ψ). In some embodiments, polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) comprise 1-methyl-pseudouridine (m1ψ) and 5-methyl-cytidine (m5C). In some embodiments, polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) comprise 2-thiouridine (s2U). In some embodiments, polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) comprise 2-thiouridine and 5-methyl-cytidine (m5C). In some embodiments, polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) comprise methoxy-uridine (mo5U). In some embodiments, polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) comprise 5-methoxy-uridine (mo5U) and 5-methyl-cytidine (m5C). In some embodiments, polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) comprise 2′-O-methyl uridine. In some embodiments polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) comprise 2′-O-methyl uridine and 5-methyl-cytidine (m5C). In some embodiments, polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) comprise N6-methyl-adenosine (m6A). In some embodiments, polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) comprise N6-methyl-adenosine (m6A) and 5-methyl-cytidine (m5C).


In some embodiments, polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) are uniformly modified (e.g., fully modified, modified throughout the entire sequence) for a particular modification. For example, a polynucleotide can be uniformly modified with 5-methyl-cytidine (m5C), meaning that all cytosine residues in the mRNA sequence are replaced with 5-methyl-cytidine (m5C). Similarly, a polynucleotide can be uniformly modified for any type of nucleoside residue present in the sequence by replacement with a modified residue such as those set forth above.


Exemplary nucleobases and nucleosides having a modified cytosine include N4-acetyl-cytidine (ac4C), 5-methyl-cytidine (m5C), 5-halo-cytidine (e.g., 5-iodo-cytidine), 5-hydroxymethyl-cytidine (hm5C), 1-methyl-pseudoisocytidine, 2-thio-cytidine (s2C), and 2-thio-5-methyl-cytidine.


In some embodiments, a modified nucleobase is a modified uridine. Exemplary nucleobases and In some embodiments, a modified nucleobase is a modified cytosine. nucleosides having a modified uridine include 5-cyano uridine, and 4′-thio uridine.


In some embodiments, a modified nucleobase is a modified adenine. Exemplary nucleobases and nucleosides having a modified adenine include 7-deaza-adenine, 1-methyl-adenosine (m1A), 2-methyl-adenine (m2A), and N6-methyl-adenosine (m6A).


In some embodiments, a modified nucleobase is a modified guanine. Exemplary nucleobases and nucleosides having a modified guanine include inosine (I), 1-methyl-inosine (m1I), wyosine (imG), methylwyosine (mimG), 7-deaza-guanosine, 7-cyano-7-deaza-guanosine (preQ0), 7-aminomethyl-7-deaza-guanosine (preQ1), 7-methyl-guanosine (m7G), 1-methyl-guanosine (m1G), 8-oxo-guanosine, 7-methyl-8-oxo-guanosine.


The polynucleotides of the present disclosure may be partially or fully modified along the entire length of the molecule. For example, one or more or all or a given type of nucleotide (e.g., purine or pyrimidine, or any one or more or all of A, G, U, C) may be uniformly modified in a polynucleotide of the invention, or in a given predetermined sequence region thereof (e.g., in the mRNA including or excluding the polyA tail). In some embodiments, all nucleotides X in a polynucleotide of the present disclosure (or in a given sequence region thereof) are modified nucleotides, wherein X may any one of nucleotides A, G, U, C, or any one of the combinations A+G, A+U, A+C, G+U, G+C, U+C, A+G+U, A+G+C, G+U+C or A+G+C.


The polynucleotide may contain from about 1% to about 100% modified nucleotides (either in relation to overall nucleotide content, or in relation to one or more types of nucleotide, i.e., any one or more of A, G, U or C) or any intervening percentage (e.g., from 1% to 20%, from 1% to 25%, from 1% to 50%, from 1% to 60%, from 1% to 70%, from 1% to 80%, from 1% to 90%, from 1% to 95%, from 10% to 20%, from 10% to 25%, from 10% to 50%, from 10% to 60%, from 10% to 70%, from 10% to 80%, from 10% to 90%, from 10% to 95%, from 10% to 100%, from 20% to 25%, from 20% to 50%, from 20% to 60%, from 20% to 70%, from 20% to 80%, from 20% to 90%, from 20% to 95%, from 20% to 100%, from 50% to 60%, from 50% to 70%, from 50% to 80%, from 50% to 90%, from 50% to 95%, from 50% to 100%, from 70% to 80%, from 70% to 90%, from 70% to 95%, from 70% to 100%, from 80% to 90%, from 80% to 95%, from 80% to 100%, from 90% to 95%, from 90% to 100%, and from 95% to 100%). Any remaining percentage is accounted for by the presence of unmodified A, G, U, or C.


The polynucleotides may contain at a minimum 1% and at maximum 100% modified nucleotides, or any intervening percentage, such as at least 5% modified nucleotides, at least 10% modified nucleotides, at least 25% modified nucleotides, at least 50% modified nucleotides, at least 80% modified nucleotides, or at least 90% modified nucleotides. For example, the polynucleotides may contain a modified pyrimidine such as a modified uracil or cytosine. In some embodiments, at least 5%, at least 10%, at least 25%, at least 50%, at least 80%, at least 90% or 100% of the uracil in the polynucleotide is replaced with a modified uracil (e.g., a 5-substituted uracil). The modified uracil can be replaced by a compound having a single unique structure, or can be replaced by a plurality of compounds having different structures (e.g., 2, 3, 4 or more unique structures). n some embodiments, at least 5%, at least 10%, at least 25%, at least 50%, at least 80%, at least 90% or 100% of the cytosine in the polynucleotide is replaced with a modified cytosine (e.g., a 5-substituted cytosine). The modified cytosine can be replaced by a compound having a single unique structure, or can be replaced by a plurality of compounds having different structures (e.g., 2, 3, 4 or more unique structures).


Thus, in some embodiments, the RNA (e.g., mRNA) vaccines comprise a 5′UTR element, an optionally codon optimized open reading frame, and a 3′UTR element, a poly(A) sequence and/or a polyadenylation signal wherein the RNA is not chemically modified.


In some embodiments, the modified nucleobase is a modified uracil. Exemplary nucleobases and nucleosides having a modified uracil include pseudouridine (ψ), pyridin-4-one ribonucleoside, 5-aza-uridine, 6-aza-uridine, 2-thio-5-aza-uridine, 2-thio-uridine (s2U), 4-thio-uridine (s4U), 4-thio-pseudouridine, 2-thio-pseudouridine, 5-hydroxy-uridine (ho5U), 5-aminoallyl-uridine, 5-halo-uridine (e.g., 5-iodo-uridineor 5-bromo-uridine), 3-methyl-uridine (m3U), 5-methoxy-uridine (mo5U), uridine 5-oxyacetic acid (cmo5U), uridine 5-oxyacetic acid methyl ester (memo5U), 5-carboxymethyl-uridine (cm5U), 1-carboxymethyl-pseudouridine, 5-carboxyhydroxymethyl-uridine (chm5U), 5-carboxyhydroxymethyl-uridine methyl ester (mchm5U), 5-methoxycarbonylmethyl-uridine (mcm5U), 5-methoxycarbonylmethyl-2-thio-uridine (mcm5s2U), 5-aminomethyl-2-thio-uridine (nm5s2U), 5-methylaminomethyl-uridine (mnm5U), 5-methylaminomethyl-2-thio-uridine (mnm5s2U), 5-methylaminomethyl-2-seleno-uridine (mnm5 se2U), 5-carbamoylmethyl-uridine (ncm5U), 5-carboxymethylaminomethyl-uridine (cmnm5U), 5-carboxymethylaminomethyl-2-thio-uridine (cmnm5s2U), 5-propynyl-uridine, 1-propynyl-pseudouridine, 5-taurinomethyl-uridine (rm5U), 1-taurinomethyl-pseudouridine, 5-taurinomethyl-2-thio-uridine(m5s2U), 1-taurinomethyl-4-thio-pseudouridine, 5-methyl-uridine (m5U, i.e., having the nucleobase deoxythymine), 1-methyl-pseudouridine (m1ψ), 5-methyl-2-thio-uridine (m5s2U), 1-methyl-4-thio-pseudouridine (m1s4ψ), 4-thio-1-methyl-pseudouridine, 3-methyl-pseudouridine (m3ψ), 2-thio-1-methyl-pseudouridine, 1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-1-deaza-pseudouridine, dihydrouridine (D), dihydropseudouridine, 5,6-dihydrouridine, 5-methyl-dihydrouridine (m5D), 2-thio-dihydrouridine, 2-thio-dihydropseudouridine, 2-methoxy-uridine, 2-methoxy-4-thio-uridine, 4-methoxy-pseudouridine, 4-methoxy-2-thio-pseudouridine, N1-methyl-pseudouridine, 3-(3-amino-3-carboxypropyl)uridine (acp3U), 1-methyl-3-(3-amino-3-carboxypropyl)pseudouridine (acp3ψ), 5-(isopentenylaminomethyl)uridine (inm5U), 5-(isopentenylaminomethyl)-2-thio-uridine (inm5s2U), α-thio-uridine, 2′-O-methyl-uridine (Um), 5,2′-O-dimethyl-uridine (m5Um), 2′-O-methyl-pseudouridine (Wm), 2-thio-2′-O-methyl-uridine (s2Um), 5-methoxycarbonylmethyl-2′-O-methyl-uridine (mcm5Um), 5-carbamoylmethyl-2′-O-methyl-uridine (ncm5Um), 5-carboxymethylaminomethyl-2′-O-methyl-uridine (cmnm5Um), 3,2′-O-dimethyl-uridine (m3Um), and 5-(isopentenylaminomethyl)-2′-O-methyl-uridine (inm5Um), 1-thio-uridine, deoxythymidine, 2′-F-ara-uridine, 2′-F-uridine, 2′-OH-ara-uridine, 5-(2-carbomethoxyvinyl) uridine, and 5-[3-(1-E-propenylamino)]uridine.


In some embodiments, the modified nucleobase is a modified cytosine. Exemplary nucleobases and nucleosides having a modified cytosine include 5-aza-cytidine, 6-aza-cytidine, pseudoisocytidine, 3-methyl-cytidine (m3C), N4-acetyl-cytidine (ac4C), 5-formyl-cytidine (f5C), N4-methyl-cytidine (m4C), 5-methyl-cytidine (m5C), 5-halo-cytidine (e.g., 5-iodo-cytidine), 5-hydroxymethyl-cytidine (hm5C), 1-methyl-pseudoisocytidine, pyrrolo-cytidine, pyrrolo-pseudoisocytidine, 2-thio-cytidine (s2C), 2-thio-5-methyl-cytidine, 4-thio-pseudoisocytidine, 4-thio-1-methyl-pseudoisocytidine, 4-thio-1-methyl-1-deaza-pseudoisocytidine, 1-methyl-1-deaza-pseudoisocytidine, zebularine, 5-aza-zebularine, 5-methyl-zebularine, 5-aza-2-thio-zebularine, 2-thio-zebularine, 2-methoxy-cytidine, 2-methoxy-5-methyl-cytidine, 4-methoxy-pseudoisocytidine, 4-methoxy-1-methyl-pseudoisocytidine, lysidine (k2C), α-thio-cytidine, 2′-O-methyl-cytidine (Cm), 5,2′-O-dimethyl-cytidine (m5Cm), N4-acetyl-2′-O-methyl-cytidine (ac4Cm), N4,2′-O-dimethyl-cytidine (m4Cm), 5-formyl-2′-O-methyl-cytidine (f5Cm), N4,N4,2′-O-trimethyl-cytidine (m24Cm), 1-thio-cytidine, 2′-F-ara-cytidine, 2′-F-cytidine, and 2′-OH-ara-cytidine.


In some embodiments, the modified nucleobase is a modified adenine. Exemplary nucleobases and nucleosides having a modified adenine include 2-amino-purine, 2, 6-diaminopurine, 2-amino-6-halo-purine (e.g., 2-amino-6-chloro-purine), 6-halo-purine (e.g., 6-chloro-purine), 2-amino-6-methyl-purine, 8-azido-adenosine, 7-deaza-adenine, 7-deaza-8-aza-adenine, 7-deaza-2-amino-purine, 7-deaza-8-aza-2-amino-purine, 7-deaza-2,6-diaminopurine, 7-deaza-8-aza-2,6-diaminopurine, 1-methyl-adenosine (m1A), 2-methyl-adenine (m2A), N6-methyl-adenosine (m6A), 2-methylthio-N6-methyl-adenosine (ms2m6A), N6-isopentenyl-adenosine (i6A), 2-methylthio-N6-isopentenyl-adenosine (ms2i6A), N6-(cis-hydroxyisopentenyl)adenosine (io6A), 2-methylthio-N6-(cis-hydroxyisopentenyl)adenosine (ms2io6A), N6-glycinylcarbamoyl-adenosine (g6A), N6-threonylcarbamoyl-adenosine (t6A), N6-methyl-N6-threonylcarbamoyl-adenosine (m6t6A), 2-methylthio-N6-threonylcarbamoyl-adenosine (ms296A), N6,N6-dimethyl-adenosine (m26A), N6-hydroxynorvalylcarbamoyl-adenosine (hn6A), 2-methylthio-N6-hydroxynorvalylcarbamoyl-adenosine (ms2hn6A), N6-acetyl-adenosine (ac6A), 7-methyl-adenine, 2-methylthio-adenine, 2-methoxy-adenine, α-thio-adenosine, 2′-O-methyl-adenosine (Am), N6,2′-O-dimethyl-adenosine (m6Am), N6,N6,2′-O-trimethyl-adenosine (m26Am), 1,2′-O-dimethyl-adenosine (m1Am), 2′-O-ribosyladenosine (phosphate) (Ar(p)), 2-amino-N6-methyl-purine, 1-thio-adenosine, 8-azido-adenosine, 2′-F-ara-adenosine, 2′-F-adenosine, 2′-OH-ara-adenosine, and N6-(19-amino-pentaoxanonadecyl)-adenosine.


In some embodiments, the modified nucleobase is a modified guanine. Exemplary nucleobases and nucleosides having a modified guanine include inosine (I), 1-methyl-inosine (m1I), wyosine (imG), methylwyosine (mimG), 4-demethyl-wyosine (imG-14), isowyosine (imG2), wybutosine (yW), peroxywybutosine (o2yW), hydroxywybutosine (OhyW), undermodified hydroxywybutosine (OhyW*), 7-deaza-guanosine, queuosine (Q), epoxyqueuosine (oQ), galactosyl-queuosine (galQ), mannosyl-queuosine (manQ), 7-cyano-7-deaza-guanosine (preQ0), 7-aminomethyl-7-deaza-guanosine (preQ1), archaeosine (G+), 7-deaza-8-aza-guanosine, 6-thio-guanosine, 6-thio-7-deaza-guanosine, 6-thio-7-deaza-8-aza-guanosine, 7-methyl-guanosine (m7G), 6-thio-7-methyl-guanosine, 7-methyl-inosine, 6-methoxy-guanosine, 1-methyl-guanosine (m1G), N2-methyl-guanosine (m2G), N2,N2-dimethyl-guanosine (m22G), N2,7-dimethyl-guanosine (m2,7G), N2, N2,7-dimethyl-guanosine (m2,2,7G), 8-oxo-guanosine, 7-methyl-8-oxo-guanosine, 1-methyl-6-thio-guanosine, N2-methyl-6-thio-guanosine, N2,N2-dimethyl-6-thio-guanosine, α-thio-guanosine, 2′-O-methyl-guanosine (Gm), N2-methyl-2′-O-methyl-guanosine (m2Gm), N2,N2-dimethyl-2′-O-methyl-guanosine (m22Gm), 1-methyl-2′-O-methyl-guanosine (m1Gm), N2,7-dimethyl-2′-O-methyl-guanosine (m2,7Gm), 2′-O-methyl-inosine (Im), 1,2′-O-dimethyl-inosine (m1Im), 2′-O-ribosylguanosine (phosphate) (Gr(p)), 1-thio-guanosine, 06-methyl-guanosine, 2′-F-ara-guanosine, and 2′-F-guanosine.


In Vitro Transcription of RNA (e.g., mRNA)


Influenza virus vaccines of the present disclosure comprise at least one RNA polynucleotide, such as a mRNA (e.g., modified mRNA). mRNA, for example, is transcribed in vitro from template DNA, referred to as an “in vitro transcription template.” In some embodiments, an in vitro transcription template encodes a 5′ untranslated (UTR) region, contains an open reading frame, and encodes a 3′ UTR and a polyA tail. The particular nucleic acid sequence composition and length of an in vitro transcription template will depend on the mRNA encoded by the template.


A “5′ untranslated region” (5′UTR) refers to a region of an mRNA that is directly upstream (i.e., 5′) from the start codon (i.e., the first codon of an mRNA transcript translated by a ribosome) that does not encode a polypeptide.


A “3′ untranslated region” (3′UTR) refers to a region of an mRNA that is directly downstream (i.e., 3′) from the stop codon (i.e., the codon of an mRNA transcript that signals a termination of translation) that does not encode a polypeptide.


An “open reading frame” is a continuous stretch of DNA or RNA beginning with a start codon (e.g., methionine (ATG or AUG)), and ending with a stop codon (e.g., TAA, TAG or TGA, or UAA, UAG or UGA) and typically encodes a polypeptide (e.g., protein).


A “polyA tail” is a region of mRNA that is downstream, e.g., directly downstream (i.e., 3′), from the 3′ UTR that contains multiple, consecutive adenosine monophosphates. A polyA tail may contain 10 to 300 adenosine monophosphates. For example, a polyA tail may contain 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290 or 300 adenosine monophosphates. In some embodiments, a polyA tail contains 50 to 250 adenosine monophosphates. In a relevant biological setting (e.g., in cells, in vivo) the poly(A) tail functions to protect mRNA from enzymatic degradation, e.g., in the cytoplasm, and aids in transcription termination, export of the mRNA from the nucleus and translation.


In some embodiments, a polynucleotide includes 200 to 3,000 nucleotides. For example, a polynucleotide may include 200 to 500, 200 to 1000, 200 to 1500, 200 to 3000, 500 to 1000, 500 to 1500, 500 to 2000, 500 to 3000, 1000 to 1500, 1000 to 2000, 1000 to 3000, 1500 to 3000, or 2000 to 3000 nucleotides.


Flagellin Adjuvants

Flagellin is an approximately 500 amino acid monomeric protein that polymerizes to form the flagella associated with bacterial motion. Flagellin is expressed by a variety of flagellated bacteria (Salmonella typhimurium for example) as well as non-flagellated bacteria (such as Escherichia coli). Sensing of flagellin by cells of the innate immune system (dendritic cells, macrophages, etc.) is mediated by the Toll-like receptor 5 (TLR5) as well as by Nod-like receptors (NLRs) Ipaf and Naip5. TLRs and NLRs have been identified as playing a role in the activation of innate immune response and adaptive immune response. As such, flagellin provides an adjuvant effect in a vaccine.


The nucleotide and amino acid sequences encoding known flagellin polypeptides are publicly available in the NCBI GenBank database. The flagellin sequences from S. Typhimurium, H. Pylori, V. Cholera, S. marcesens, S. flexneri, T. Pallidum, L. pneumophila, B. burgdorferei, C. difficile, R. meliloti, A. tumefaciens, R. lupini, B. clarridgeiae, P. Mirabilis, B. subtilus, L. monocytogenes, P. aeruginosa, and E. coli, among others are known.


A flagellin polypeptide, as used herein, refers to a full length flagellin protein, immunogenic fragments thereof, and peptides having at least 50% sequence identify to a flagellin protein or immunogenic fragments thereof. Exemplary flagellin proteins include flagellin from Salmonella typhi (UniPro Entry number: Q56086), Salmonella typhimurium (AOAOC9DG09), Salmonella enteritidis (AOAOC9BAB7), and Salmonella choleraesuis (Q6V2X8), and proteins having an amino acid sequence identified by any one of SEQ ID NO 1-444, 458, 460, 462-479, or 543-565 (see also Tables 7-13 and 26). In some embodiments, the flagellin polypeptide has at least 60%, 70%, 75%, 80%, 90%, 95%, 97%, 98%, or 99% sequence identify to a flagellin protein or immunogenic fragments thereof.


In some embodiments, the flagellin polypeptide is an immunogenic fragment. An immunogenic fragment is a portion of a flagellin protein that provokes an immune response. In some embodiments, the immune response is a TLR5 immune response. An example of an immunogenic fragment is a flagellin protein in which all or a portion of a hinge region has been deleted or replaced with other amino acids. For example, an antigenic polypeptide may be inserted in the hinge region. Hinge regions are the hypervariable regions of a flagellin. Hinge regions of a flagellin are also referred to as “D3 domain or region, “propeller domain or region,” “hypervariable domain or region” and “variable domain or region.” “At least a portion of a hinge region,” as used herein, refers to any part of the hinge region of the flagellin, or the entirety of the hinge region. In other embodiments an immunogenic fragment of flagellin is a 20, 25, 30, 35, or 40 amino acid C-terminal fragment of flagellin.


The flagellin monomer is formed by domains D0 through D3. D0 and D1, which form the stem, are composed of tandem long alpha helices and are highly conserved among different bacteria. The D1 domain includes several stretches of amino acids that are useful for TLR5 activation. The entire D1 domain or one or more of the active regions within the domain are immunogenic fragments of flagellin. Examples of immunogenic regions within the D1 domain include residues 88-114 and residues 411-431 (in Salmonella typhimurium FliC flagellin. Within the 13 amino acids in the 88-100 region, at least 6 substitutions are permitted between Salmonella flagellin and other flagellins that still preserve TLR5 activation. Thus, immunogenic fragments of flagellin include flagellin like sequences that activate TLR5 and contain a 13 amino acid motif that is 53% or more identical to the Salmonella sequence in 88-100 of FliC (LQRVRELAVQSAN; SEQ ID NO: 504).


In some embodiments, the RNA (e.g., mRNA) vaccine includes an RNA that encodes a fusion protein of flagellin and one or more antigenic polypeptides. A “fusion protein” as used herein, refers to a linking of two components of the construct. In some embodiments, a carboxy-terminus of the antigenic polypeptide is fused or linked to an amino terminus of the flagellin polypeptide. In other embodiments, an amino-terminus of the antigenic polypeptide is fused or linked to a carboxy-terminus of the flagellin polypeptide. The fusion protein may include, for example, one, two, three, four, five, six or more flagellin polypeptides linked to one, two, three, four, five, six or more antigenic polypeptides. When two or more flagellin polypeptides and/or two or more antigenic polypeptides are linked such a construct may be referred to as a “multimer.”


Each of the components of a fusion protein may be directly linked to one another or they may be connected through a linker. For instance, the linker may be an amino acid linker. The amino acid linker encoded for by the RNA (e.g., mRNA) vaccine to link the components of the fusion protein may include, for instance, at least one member selected from the group consisting of a lysine residue, a glutamic acid residue, a serine residue and an arginine residue. In some embodiments the linker is 1-30, 1-25, 1-25, 5-10, 5, 15, or 5-20 amino acids in length.


In other embodiments the RNA (e.g., mRNA) vaccine includes at least two separate RNA polynucleotides, one encoding one or more antigenic polypeptides and the other encoding the flagellin polypeptide. The at least two RNA polynucleotides may be co-formulated in a carrier such as a lipid nanoparticle.


Methods of Treatment

Provided herein are compositions (e.g., pharmaceutical compositions), methods, kits and reagents for prevention and/or treatment of influenza virus in humans and other mammals. Influenza virus RNA vaccines can be used as therapeutic or prophylactic agents. They may be used in medicine to prevent and/or treat infectious disease. In exemplary aspects, the influenza virus RNA vaccines of the present disclosure are used to provide prophylactic protection from influenza virus. Prophylactic protection from influenza virus can be achieved following administration of an influenza virus RNA vaccine of the present disclosure. Vaccines can be administered once, twice, three times, four times or more. It is possible, although less desirable, to administer the vaccine to an infected individual to achieve a therapeutic response. Dosing may need to be adjusted accordingly.


In some embodiments, the influenza virus vaccines of the present disclosure can be used as a method of preventing an influenza virus infection in a subject, the method comprising administering to said subject at least one influenza virus vaccine as provided herein. In some embodiments, the influenza virus vaccines of the present disclosure can be used as a method of inhibiting a primary influenza virus infection in a subject, the method comprising administering to said subject at least one influenza virus vaccine as provided herein. In some embodiments, the influenza virus vaccines of the present disclosure can be used as a method of treating an influenza virus infection in a subject, the method comprising administering to said subject at least one influenza virus vaccine as provided herein. In some embodiments, the influenza virus vaccines of the present disclosure can be used as a method of reducing an incidence of influenza virus infection in a subject, the method comprising administering to said subject at least one influenza virus vaccine as provided herein. In come embodiments, the influenza virus vaccines of the present disclosure can be used as a method of inhibiting spread of influenza virus from a first subject infected with influenza virus to a second subject not infected with influenza virus, the method comprising administering to at least one of said first subject sand said second subject at least one influenza virus vaccine as provided herein.


A method of eliciting an immune response in a subject against an influenza virus is provided in aspects of the invention. The method involves administering to the subject an influenza virus RNA vaccine comprising at least one RNA polynucleotide having an open reading frame encoding at least one influenza virus antigenic polypeptide, thereby inducing in the subject an immune response specific to influenza virus antigenic polypeptide, wherein anti-antigenic polypeptide antibody titer in the subject is increased following vaccination relative to anti-antigenic polypeptide antibody titer in a subject vaccinated with a prophylactically effective dose of a traditional vaccine against the influenza virus. An “anti-antigenic polypeptide antibody” is a serum antibody the binds specifically to the antigenic polypeptide.


A prophylactically effective dose is a therapeutically effective dose that prevents infection with the virus at a clinically acceptable level. In some embodiments the therapeutically effective dose is a dose listed in a package insert for the vaccine. A traditional vaccine, as used herein, refers to a vaccine other than the mRNA vaccines of the present disclosure. For instance, a traditional vaccine includes, but is not limited to, live microorganism vaccines, killed microorganism vaccines, subunit vaccines, protein antigen vaccines, DNA vaccines, VLP vaccines, etc. In exemplary embodiments, a traditional vaccine is a vaccine that has achieved regulatory approval and/or is registered by a national drug regulatory body, for example the Food and Drug Administration (FDA) in the United States or the European Medicines Agency (EMA).


In some embodiments the anti-antigenic polypeptide antibody titer in the subject is increased 1 log to 10 log following vaccination relative to anti-antigenic polypeptide antibody titer in a subject vaccinated with a prophylactically effective dose of a traditional vaccine against the influenza virus.


In some embodiments the anti-antigenic polypeptide antibody titer in the subject is increased 1 log, 2 log, 3 log, 5 log or 10 log following vaccination relative to anti-antigenic polypeptide antibody titer in a subject vaccinated with a prophylactically effective dose of a traditional vaccine against influenza.


A method of eliciting an immune response in a subject against an influenza virus is provided in other aspects of the present disclosure. The method involves administering to the subject an influenza virus RNA vaccine comprising at least one RNA polynucleotide having an open reading frame encoding at least one influenza virus antigenic polypeptide, thereby inducing in the subject an immune response specific to influenza virus antigenic polypeptide, wherein the immune response in the subject is equivalent to an immune response in a subject vaccinated with a traditional vaccine against the influenza virus at 2 times to 100 times the dosage level relative to the RNA vaccine.


In some embodiments, the immune response in the subject is equivalent to an immune response in a subject vaccinated with a traditional vaccine at 2, 3, 4, 5, 10, 50, 100 times the dosage level relative to the influenza vaccine.


In some embodiments the immune response in the subject is equivalent to an immune response in a subject vaccinated with a traditional vaccine at 10-100 times, or 100-1000 times, the dosage level relative to the influenza vaccine.


In some embodiments the immune response is assessed by determining [protein] antibody titer in the subject.


Some embodiments provide a method of inducing an immune response in a subject by administering to the subject an influenza RNA (e.g., mRNA) vaccine comprising at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding at least one influenza antigenic polypeptide, thereby inducing in the subject an immune response specific to the antigenic polypeptide, wherein the immune response in the subject is induced 2 days to 10 weeks earlier relative to an immune response induced in a subject vaccinated with a prophylactically effective dose of a traditional vaccine against influenza. In some embodiments, the immune response in the subject is induced in a subject vaccinated with a prophylactically effective dose of a traditional vaccine at 2 times to 100 times the dosage level relative to the influenza RNA (e.g., mRNA) vaccine.


In some embodiments the immune response in the subject is equivalent to an immune response in a subject vaccinated with a traditional vaccine at 2, 3, 4, 5, 10, 50, 100 times the dosage level relative to the influenza RNA (e.g., mRNA) vaccine.


In some embodiments, the immune response in the subject is induced 2 days earlier, or 3 days earlier, relative to an immune response induced in a subject vaccinated with a prophylactically effective dose of a traditional vaccine.


In some embodiments the immune response in the subject is induced 1 week, 2 weeks, 3 weeks, 5 weeks, or 10 weeks earlier relative to an immune response induced in a subject vaccinated with a prophylactically effective dose of a traditional vaccine.


Therapeutic and Prophylactic Compositions

Provided herein are compositions (e.g., pharmaceutical compositions), methods, kits and reagents for prevention, treatment or diagnosis of influenza in humans and other mammals, for example. Influenza RNA (e.g. mRNA) vaccines can be used as therapeutic or prophylactic agents. They may be used in medicine to prevent and/or treat infectious disease. In some embodiments, the respiratory RNA (e.g., mRNA) vaccines of the present disclosure are used fin the priming of immune effector cells, for example, to activate peripheral blood mononuclear cells (PBMCs) ex vivo, which are then infused (re-infused) into a subject.


In some embodiments, influenza vaccine containing RNA (e.g., mRNA) polynucleotides as described herein can be administered to a subject (e.g., a mammalian subject, such as a human subject), and the RNA (e.g., mRNA) polynucleotides are translated in vivo to produce an antigenic polypeptide.


The influenza RNA (e.g., mRNA) vaccines may be induced for translation of a polypeptide (e.g., antigen or immunogen) in a cell, tissue or organism. In some embodiments, such translation occurs in vivo, although such translation may occur ex vivo, in culture or in vitro. In some embodiments, the cell, tissue or organism is contacted with an effective amount of a composition containing an influenza RNA (e.g., mRNA) vaccine that contains a polynucleotide that has at least one a translatable region encoding an antigenic polypeptide.


An “effective amount” of an influenza RNA (e.g. mRNA) vaccine is provided based, at least in part, on the target tissue, target cell type, means of administration, physical characteristics of the polynucleotide (e.g., size, and extent of modified nucleosides) and other components of the vaccine, and other determinants. In general, an effective amount of the influenza RNA (e.g., mRNA) vaccine composition provides an induced or boosted immune response as a function of antigen production in the cell, preferably more efficient than a composition containing a corresponding unmodified polynucleotide encoding the same antigen or a peptide antigen. Increased antigen production may be demonstrated by increased cell transfection (the percentage of cells transfected with the RNA, e.g., mRNA, vaccine), increased protein translation from the polynucleotide, decreased nucleic acid degradation (as demonstrated, for example, by increased duration of protein translation from a modified polynucleotide), or altered antigen specific immune response of the host cell.


In some embodiments, RNA (e.g. mRNA) vaccines (including polynucleotides their encoded polypeptides) in accordance with the present disclosure may be used for treatment of Influenza.


Influenza RNA (e.g. mRNA) vaccines may be administered prophylactically or therapeutically as part of an active immunization scheme to healthy individuals or early in infection during the incubation phase or during active infection after onset of symptoms. In some embodiments, the amount of RNA (e.g., mRNA) vaccine of the present disclosure provided to a cell, a tissue or a subject may be an amount effective for immune prophylaxis.


Influenza RNA (e.g. mRNA) vaccines may be administrated with other prophylactic or therapeutic compounds. As a non-limiting example, a prophylactic or therapeutic compound may be an adjuvant or a booster. As used herein, when referring to a prophylactic composition, such as a vaccine, the term “booster” refers to an extra administration of the prophylactic (vaccine) composition. A booster (or booster vaccine) may be given after an earlier administration of the prophylactic composition. The time of administration between the initial administration of the prophylactic composition and the booster may be, but is not limited to, 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 6 minutes, 7 minutes, 8 minutes, 9 minutes, 10 minutes, 15 minutes, 20 minutes 35 minutes, 40 minutes, 45 minutes, 50 minutes, 55 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 1 day, 36 hours, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 10 days, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 18 months, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, 11 years, 12 years, 13 years, 14 years, 15 years, 16 years, 17 years, 18 years, 19 years, 20 years, 25 years, 30 years, 35 years, 40 years, 45 years, 50 years, 55 years, 60 years, 65 years, 70 years, 75 years, 80 years, 85 years, 90 years, 95 years or more than 99 years. In some embodiments, the time of administration between the initial administration of the prophylactic composition and the booster may be, but is not limited to, 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 6 months or 1 year.


In some embodiments, influenza RNA (e.g. mRNA) vaccines may be administered intramuscularly, intradermally, or intranasally, similarly to the administration of inactivated vaccines known in the art. In some embodiments, influenza RNA (e.g. mRNA) vaccines are administered intramuscularly.


Influenza RNA (e.g. mRNA) vaccines may be utilized in various settings depending on the prevalence of the infection or the degree or level of unmet medical need. As a non-limiting example, the RNA (e.g., mRNA) vaccines may be utilized to treat and/or prevent a variety of influenzas. RNA (e.g., mRNA) vaccines have superior properties in that they produce much larger antibody titers and produce responses early than commercially available anti-viral agents/compositions.


Provided herein are pharmaceutical compositions including influenza RNA (e.g. mRNA) vaccines and RNA (e.g. mRNA) vaccine compositions and/or complexes optionally in combination with one or more pharmaceutically acceptable excipients.


Influenza RNA (e.g. mRNA) vaccines may be formulated or administered alone or in conjunction with one or more other components. For instance, Influenza RNA (e.g., mRNA) vaccines (vaccine compositions) may comprise other components including, but not limited to, adjuvants.


In some embodiments, influenza (e.g. mRNA) vaccines do not include an adjuvant (they are adjuvant free).


Influenza RNA (e.g. mRNA) vaccines may be formulated or administered in combination with one or more pharmaceutically-acceptable excipients. In some embodiments, vaccine compositions comprise at least one additional active substances, such as, for example, a therapeutically-active substance, a prophylactically-active substance, or a combination of both. Vaccine compositions may be sterile, pyrogen-free or both sterile and pyrogen-free. General considerations in the formulation and/or manufacture of pharmaceutical agents, such as vaccine compositions, may be found, for example, in Remington: The Science and Practice of Pharmacy 21st ed., Lippincott Williams & Wilkins, 2005 (incorporated herein by reference in its entirety).


In some embodiments, influenza RNA (e.g. mRNA) vaccines are administered to humans, human patients or subjects. For the purposes of the present disclosure, the phrase “active ingredient” generally refers to the RNA (e.g., mRNA) vaccines or the polynucleotides contained therein, for example, RNA polynucleotides (e.g., mRNA polynucleotides) encoding antigenic polypeptides.


Formulations of the influenza vaccine compositions described herein may be prepared by any method known or hereafter developed in the art of pharmacology. In general, such preparatory methods include the step of bringing the active ingredient (e.g., mRNA polynucleotide) into association with an excipient and/or one or more other accessory ingredients, and then, if necessary and/or desirable, dividing, shaping and/or packaging the product into a desired single- or multi-dose unit.


Relative amounts of the active ingredient, the pharmaceutically acceptable excipient, and/or any additional ingredients in a pharmaceutical composition in accordance with the disclosure will vary, depending upon the identity, size, and/or condition of the subject treated and further depending upon the route by which the composition is to be administered. By way of example, the composition may comprise between 0.1% and 100%, e.g., between 0.5 and 50%, between 1-30%, between 5-80%, at least 80% (w/w) active ingredient.


Influenza RNA (e.g. mRNA) vaccines can be formulated using one or more excipients to: increase stability; increase cell transfection; permit the sustained or delayed release (e.g., from a depot formulation); alter the biodistribution (e.g., target to specific tissues or cell types); increase the translation of encoded protein in vivo; and/or alter the release profile of encoded protein (antigen) in vivo. In addition to traditional excipients such as any and all solvents, dispersion media, diluents, or other liquid vehicles, dispersion or suspension aids, surface active agents, isotonic agents, thickening or emulsifying agents, preservatives, excipients can include, without limitation, lipidoids, liposomes, lipid nanoparticles, polymers, lipoplexes, core-shell nanoparticles, peptides, proteins, cells transfected with influenza RNA (e.g. mRNA)vaccines (e.g., for transplantation into a subject), hyaluronidase, nanoparticle mimics and combinations thereof.


Stabilizing Elements

Naturally-occurring eukaryotic mRNA molecules have been found to contain stabilizing elements, including, but not limited to untranslated regions (UTR) at their 5′-end (5′UTR) and/or at their 3′-end (3′UTR), in addition to other structural features, such as a 5′-cap structure or a 3′-poly(A) tail. Both the 5′UTR and the 3′UTR are typically transcribed from the genomic DNA and are elements of the premature mRNA. Characteristic structural features of mature mRNA, such as the 5′-cap and the 3′-poly(A) tail are usually added to the transcribed (premature) mRNA during mRNA processing. The 3′-poly(A) tail is typically a stretch of adenine nucleotides added to the 3′-end of the transcribed mRNA. It can comprise up to about 400 adenine nucleotides. In some embodiments the length of the 3′-poly(A) tail may be an essential element with respect to the stability of the individual mRNA.


In some embodiments the RNA (e.g., mRNA) vaccine may include one or more stabilizing elements. Stabilizing elements may include for instance a histone stem-loop. A stem-loop binding protein (SLBP), a 32 kDa protein has been identified. It is associated with the histone stem-loop at the 3′-end of the histone messages in both the nucleus and the cytoplasm. Its expression level is regulated by the cell cycle; it is peaks during the S-phase, when histone mRNA levels are also elevated. The protein has been shown to be essential for efficient 3′-end processing of histone pre-mRNA by the U7 snRNP. SLBP continues to be associated with the stem-loop after processing, and then stimulates the translation of mature histone mRNAs into histone proteins in the cytoplasm. The RNA binding domain of SLBP is conserved through metazoa and protozoa; its binding to the histone stem-loop depends on the structure of the loop. The minimum binding site includes at least three nucleotides 5′ and two nucleotides 3′ relative to the stem-loop.


In some embodiments, the RNA (e.g., mRNA) vaccines include a coding region, at least one histone stem-loop, and optionally, a poly(A) sequence or polyadenylation signal. The poly(A) sequence or polyadenylation signal generally should enhance the expression level of the encoded protein. The encoded protein, in some embodiments, is not a histone protein, a reporter protein (e.g. Luciferase, GFP, EGFP, β-Galactosidase, EGFP), or a marker or selection protein (e.g. alpha-Globin, Galactokinase and Xanthine:guanine phosphoribosyl transferase (GPT)).


In some embodiments, the combination of a poly(A) sequence or polyadenylation signal and at least one histone stem-loop, even though both represent alternative mechanisms in nature, acts synergistically to increase the protein expression beyond the level observed with either of the individual elements. It has been found that the synergistic effect of the combination of poly(A) and at least one histone stem-loop does not depend on the order of the elements or the length of the poly(A) sequence.


In some embodiments, the RNA (e.g., mRNA) vaccine does not comprise a histone downstream element (HDE). “Histone downstream element” (HDE) includes a purine-rich polynucleotide stretch of approximately 15 to 20 nucleotides 3′ of naturally occurring stem-loops, representing the binding site for the U7 snRNA, which is involved in processing of histone pre-mRNA into mature histone mRNA. Ideally, the inventive nucleic acid does not include an intron.


In some embodiments, the RNA (e.g., mRNA) vaccine may or may not contain a enhancer and/or promoter sequence, which may be modified or unmodified or which may be activated or inactivated. In some embodiments, the histone stem-loop is generally derived from histone genes, and includes an intramolecular base pairing of two neighbored partially or entirely reverse complementary sequences separated by a spacer, including (e.g., consisting of) a short sequence, which forms the loop of the structure. The unpaired loop region is typically unable to base pair with either of the stem loop elements. It occurs more often in RNA, as is a key component of many RNA secondary structures, but may be present in single-stranded DNA as well. Stability of the stem-loop structure generally depends on the length, number of mismatches or bulges, and base composition of the paired region. In some embodiments, wobble base pairing (non-Watson-Crick base pairing) may result. In some embodiments, the at least one histone stem-loop sequence comprises a length of 15 to 45 nucleotides.


In other embodiments the RNA (e.g., mRNA) vaccine may have one or more AU-rich sequences removed. These sequences, sometimes referred to as AURES are destabilizing sequences found in the 3′UTR. The AURES may be removed from the RNA (e.g., mRNA) vaccines. Alternatively the AURES may remain in the RNA (e.g., mRNA) vaccine.


Nanoparticle Formulations

In some embodiments, influenza RNA (e.g. mRNA) vaccines are formulated in a nanoparticle. In some embodiments, influenza RNA (e.g. mRNA) vaccines are formulated in a lipid nanoparticle. In some embodiments, influenza RNA (e.g. mRNA) vaccines are formulated in a lipid-polycation complex, referred to as a cationic lipid nanoparticle. As a non-limiting example, the polycation may include a cationic peptide or a polypeptide such as, but not limited to, polylysine, polyornithine and/or polyarginine. In some embodiments, influenza RNA (e.g., mRNA) vaccines are formulated in a lipid nanoparticle that includes a non-cationic lipid such as, but not limited to, cholesterol or dioleoyl phosphatidylethanolamine (DOPE).


A lipid nanoparticle formulation may be influenced by, but not limited to, the selection of the cationic lipid component, the degree of cationic lipid saturation, the nature of the PEGylation, ratio of all components and biophysical parameters such as size. In one example by Semple et al. (Nature Biotech. 2010 28:172-176), the lipid nanoparticle formulation is composed of 57.1% cationic lipid, 7.1% dipalmitoylphosphatidylcholine, 34.3% cholesterol, and 1.4% PEG-c-DMA. As another example, changing the composition of the cationic lipid can more effectively deliver siRNA to various antigen presenting cells (Basha et al. Mol Ther. 2011 19:2186-2200).


In some embodiments, lipid nanoparticle formulations may comprise 35 to 45% cationic lipid, 40% to 50% cationic lipid, 50% to 60% cationic lipid and/or 55% to 65% cationic lipid. In some embodiments, the ratio of lipid to RNA (e.g., mRNA) in lipid nanoparticles may be 5:1 to 20:1, 10:1 to 25:1, 15:1 to 30:1 and/or at least 30:1.


In some embodiments, the ratio of PEG in the lipid nanoparticle formulations may be increased or decreased and/or the carbon chain length of the PEG lipid may be modified from C14 to C18 to alter the pharmacokinetics and/or biodistribution of the lipid nanoparticle formulations. As a non-limiting example, lipid nanoparticle formulations may contain 0.5% to 3.0%, 1.0% to 3.5%, 1.5% to 4.0%, 2.0% to 4.5%, 2.5% to 5.0% and/or 3.0% to 6.0% of the lipid molar ratio of PEG-c-DOMG (R-3-[(o-methoxy-poly(ethyleneglycol)2000)carbamoyl)]-1,2-dimyristyloxypropyl-3-amine) (also referred to herein as PEG-DOMG) as compared to the cationic lipid, DSPC and cholesterol. In some embodiments, the PEG-c-DOMG may be replaced with a PEG lipid such as, but not limited to, PEG-DSG (1,2-Distearoyl-sn-glycerol, methoxypolyethylene glycol), PEG-DMG (1,2-Dimyristoyl-sn-glycerol) and/or PEG-DPG (1,2-Dipalmitoyl-sn-glycerol, methoxypolyethylene glycol). The cationic lipid may be selected from any lipid known in the art such as, but not limited to, DLin-MC3-DMA, DLin-DMA, C12-200 and DLin-KC2-DMA.


In some embodiments, an influenza RNA (e.g. mRNA) vaccine formulation is a nanoparticle that comprises at least one lipid. The lipid may be selected from, but is not limited to, DLin-DMA, DLin-K-DMA, 98N12-5, C12-200, DLin-MC3-DMA, DLin-KC2-DMA, DODMA, PLGA, PEG, PEG-DMG, PEGylated lipids and amino alcohol lipids. In some embodiments, the lipid may be a cationic lipid such as, but not limited to, DLin-DMA, DLin-D-DMA, DLin-MC3-DMA, DLin-KC2-DMA, DODMA and amino alcohol lipids. The amino alcohol cationic lipid may be the lipids described in and/or made by the methods described in U.S. Patent Publication No. US2013/0150625, herein incorporated by reference in its entirety. As a non-limiting example, the cationic lipid may be 2-amino-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-{[(9Z,2Z)-octadeca-9,12-dien-1-yloxy]methyl}propan-1-ol (Compound 1 in US2013/0150625); 2-amino-3-[(9Z)-octadec-9-en-1-yloxy]-2-{[(9Z)-octadec-9-en-1-yloxy]methyl}propan-1-ol (Compound 2 in US2013/0150625); 2-amino-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-[(octyloxy)methyl]propan-1-ol (Compound 3 in US2013/0150625); and 2-(dimethylamino)-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-{[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]methyl}propan-1-ol (Compound 4 in US2013/0150625); or any pharmaceutically acceptable salt or stereoisomer thereof.


Lipid nanoparticle formulations typically comprise a lipid, in particular, an ionizable cationic lipid, for example, 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), or di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, and further comprise a neutral lipid, a sterol and a molecule capable of reducing particle aggregation, for example a PEG or PEG-modified lipid.


In some embodiments, a lipid nanoparticle formulation consists essentially of (i) at least one lipid selected from the group consisting of 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate; (ii) a neutral lipid selected from DSPC, DPPC, POPC, DOPE and SM; (iii) a sterol, e.g., cholesterol; and (iv) a PEG-lipid, e.g., PEG-DMG or PEG-cDMA, in a molar ratio of 20-60% cationic lipid:5-25% neutral lipid: 25-55% sterol; 0.5-15% PEG-lipid.


In some embodiments, a lipid nanoparticle formulation includes 25% to 75% on a molar basis of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, e.g., 35 to 65%, 45 to 65%, 60%, 57.5%, 50% or 40% on a molar basis.


In some embodiments, a lipid nanoparticle formulation includes 0.5% to 15% on a molar basis of the neutral lipid, e.g., 3 to 12%, 5 to 10% or 15%, 10%, or 7.5% on a molar basis. Examples of neutral lipids include, without limitation, DSPC, POPC, DPPC, DOPE and SM. In some embodiments, the formulation includes 5% to 50% on a molar basis of the sterol (e.g., 15 to 45%, 20 to 40%, 40%, 38.5%, 35%, or 31% on a molar basis. A non-limiting example of a sterol is cholesterol. In some embodiments, a lipid nanoparticle formulation includes 0.5% to 20% on a molar basis of the PEG or PEG-modified lipid (e.g., 0.5 to 10%, 0.5 to 5%, 1.5%, 0.5%, 1.5%, 3.5%, or 5% on a molar basis. In some embodiments, a PEG or PEG modified lipid comprises a PEG molecule of an average molecular weight of 2,000 Da. In some embodiments, a PEG or PEG modified lipid comprises a PEG molecule of an average molecular weight of less than 2,000, for example around 1,500 Da, around 1,000 Da, or around 500 Da. Non-limiting examples of PEG-modified lipids include PEG-distearoyl glycerol (PEG-DMG) (also referred herein as PEG-C14 or C14-PEG), PEG-cDMA (further discussed in Reyes et al. J. Controlled Release, 107, 276-287 (2005) the contents of which are herein incorporated by reference in their entirety).


In some embodiments, lipid nanoparticle formulations include 25-75% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 0.5-15% of the neutral lipid, 5-50% of the sterol, and 0.5-20% of the PEG or PEG-modified lipid on a molar basis.


In some embodiments, lipid nanoparticle formulations include 35-65% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 3-12% of the neutral lipid, 15-45% of the sterol, and 0.5-10% of the PEG or PEG-modified lipid on a molar basis.


In some embodiments, lipid nanoparticle formulations include 45-65% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 5-10% of the neutral lipid, 25-40% of the sterol, and 0.5-10% of the PEG or PEG-modified lipid on a molar basis.


In some embodiments, lipid nanoparticle formulations include 60% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 7.5% of the neutral lipid, 31% of the sterol, and 1.5% of the PEG or PEG-modified lipid on a molar basis.


In some embodiments, lipid nanoparticle formulations include 50% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 10% of the neutral lipid, 38.5% of the sterol, and 1.5% of the PEG or PEG-modified lipid on a molar basis.


In some embodiments, lipid nanoparticle formulations include 50% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 10% of the neutral lipid, 35% of the sterol, 4.5% or 5% of the PEG or PEG-modified lipid, and 0.5% of the targeting lipid on a molar basis.


In some embodiments, lipid nanoparticle formulations include 40% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 15% of the neutral lipid, 40% of the sterol, and 5% of the PEG or PEG-modified lipid on a molar basis.


In some embodiments, lipid nanoparticle formulations include 57.2% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 7.1% of the neutral lipid, 34.3% of the sterol, and 1.4% of the PEG or PEG-modified lipid on a molar basis.


In some embodiments, lipid nanoparticle formulations include 57.5% of a cationic lipid selected from the PEG lipid is PEG-cDMA (PEG-cDMA is further discussed in Reyes et al. (J. Controlled Release, 107, 276-287 (2005), the contents of which are herein incorporated by reference in their entirety), 7.5% of the neutral lipid, 31.5% of the sterol, and 3.5% of the PEG or PEG-modified lipid on a molar basis.


In some embodiments, lipid nanoparticle formulations consists essentially of a lipid mixture in molar ratios of 20-70% cationic lipid: 5-45% neutral lipid: 20-55% cholesterol: 0.5-15% PEG-modified lipid. In some embodiments, lipid nanoparticle formulations consists essentially of a lipid mixture in a molar ratio of 20-60% cationic lipid:5-25% neutral lipid: 25-55% cholesterol: 0.5-15% PEG-modified lipid.


In some embodiments, the molar lipid ratio is 50/10/38.5/1.5 (mol % cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG, PEG-DSG or PEG-DPG), 57.2/7.1134.3/1.4 (mol % cationic lipid/neutral lipid, e.g., DPPC/Chol/PEG-modified lipid, e.g., PEG-cDMA), 40/15/40/5 (mol % cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG), 50/10/35/4.5/0.5 (mol % cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DSG), 50/10/35/5 (cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG), 40/10/40/10 (mol % cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG or PEG-cDMA), 35/15/40/10 (mol % cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG or PEG-cDMA) or 52/13/30/5 (mol % cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG or PEG-cDMA).


Non-limiting examples of lipid nanoparticle compositions and methods of making them are described, for example, in Semple et al. (2010) Nat. Biotechnol. 28:172-176; Jayarama et al. (2012), Angew. Chem. Int. Ed., 51: 8529-8533; and Maier et al. (2013) Molecular Therapy 21, 1570-1578 (the contents of each of which are incorporated herein by reference in their entirety).


In some embodiments, lipid nanoparticle formulations may comprise a cationic lipid, a PEG lipid and a structural lipid and optionally comprise a non-cationic lipid. As a non-limiting example, a lipid nanoparticle may comprise 40-60% of cationic lipid, 5-15% of a non-cationic lipid, 1-2% of a PEG lipid and 30-50% of a structural lipid. As another non-limiting example, the lipid nanoparticle may comprise 50% cationic lipid, 10% non-cationic lipid, 1.5% PEG lipid and 38.5% structural lipid. As yet another non-limiting example, a lipid nanoparticle may comprise 55% cationic lipid, 10% non-cationic lipid, 2.5% PEG lipid and 32.5% structural lipid. In some embodiments, the cationic lipid may be any cationic lipid described herein such as, but not limited to, DLin-KC2-DMA, DLin-MC3-DMA and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate.


In some embodiments, the lipid nanoparticle formulations described herein may be 4 component lipid nanoparticles. The lipid nanoparticle may comprise a cationic lipid, a non-cationic lipid, a PEG lipid and a structural lipid. As a non-limiting example, the lipid nanoparticle may comprise 40-60% of cationic lipid, 5-15% of a non-cationic lipid, 1-2% of a PEG lipid and 30-50% of a structural lipid. As another non-limiting example, the lipid nanoparticle may comprise 50% cationic lipid, 10% non-cationic lipid, 1.5% PEG lipid and 38.5% structural lipid. As yet another non-limiting example, the lipid nanoparticle may comprise 55% cationic lipid, 10% non-cationic lipid, 2.5% PEG lipid and 32.5% structural lipid. In some embodiments, the cationic lipid may be any cationic lipid described herein such as, but not limited to, DLin-KC2-DMA, DLin-MC3-DMA and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate.


In some embodiments, the lipid nanoparticle formulations described herein may comprise a cationic lipid, a non-cationic lipid, a PEG lipid and a structural lipid. As a non-limiting example, the lipid nanoparticle comprise 50% of the cationic lipid DLin-KC2-DMA, 10% of the non-cationic lipid DSPC, 1.5% of the PEG lipid PEG-DOMG and 38.5% of the structural lipid cholesterol. As a non-limiting example, the lipid nanoparticle comprise 50% of the cationic lipid DLin-MC3-DMA, 10% of the non-cationic lipid DSPC, 1.5% of the PEG lipid PEG-DOMG and 38.5% of the structural lipid cholesterol. As a non-limiting example, the lipid nanoparticle comprise 50% of the cationic lipid DLin-MC3-DMA, 10% of the non-cationic lipid DSPC, 1.5% of the PEG lipid PEG-DMG and 38.5% of the structural lipid cholesterol. As yet another non-limiting example, the lipid nanoparticle comprise 55% of the cationic lipid di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 10% of the non-cationic lipid DSPC, 2.5% of the PEG lipid PEG-DMG and 32.5% of the structural lipid cholesterol.


Relative amounts of the active ingredient, the pharmaceutically acceptable excipient, and/or any additional ingredients in a vaccine composition may vary, depending upon the identity, size, and/or condition of the subject being treated and further depending upon the route by which the composition is to be administered. For example, the composition may comprise between 0.1% and 99% (w/w) of the active ingredient. By way of example, the composition may comprise between 0.1% and 100%, e.g., between 0.5 and 50%, between 1-30%, between 5-80%, at least 80% (w/w) active ingredient.


In some embodiments, the influenza RNA (e.g. mRNA) vaccine composition may comprise the polynucleotide described herein, formulated in a lipid nanoparticle comprising MC3, Cholesterol, DSPC and PEG2000-DMG, the buffer trisodium citrate, sucrose and water for injection. As a non-limiting example, the composition comprises: 2.0 mg/mL of drug substance, 21.8 mg/mL of MC3, 10.1 mg/mL of cholesterol, 5.4 mg/mL of DSPC, 2.7 mg/mL of PEG2000-DMG, 5.16 mg/mL of trisodium citrate, 71 mg/mL of sucrose and 1.0 mL of water for injection.


In some embodiments, a nanoparticle (e.g., a lipid nanoparticle) has a mean diameter of 10-500 nm, 20-400 nm, 30-300 nm, 40-200 nm. In some embodiments, a nanoparticle (e.g., a lipid nanoparticle) has a mean diameter of 50-150 nm, 50-200 nm, 80-100 nm or 80-200 nm.


Liposomes, Lipoplexes, and Lipid Nanoparticles

The RNA (e.g., mRNA) vaccines of the disclosure can be formulated using one or more liposomes, lipoplexes, or lipid nanoparticles. In some embodiments, pharmaceutical compositions of RNA (e.g., mRNA) vaccines include liposomes. Liposomes are artificially-prepared vesicles which may primarily be composed of a lipid bilayer and may be used as a delivery vehicle for the administration of nutrients and pharmaceutical formulations. Liposomes can be of different sizes such as, but not limited to, a multilamellar vesicle (MLV) which may be hundreds of nanometers in diameter and may contain a series of concentric bilayers separated by narrow aqueous compartments, a small unicellular vesicle (SUV) which may be smaller than 50 nm in diameter, and a large unilamellar vesicle (LUV) which may be between 50 and 500 nm in diameter. Liposome design may include, but is not limited to, opsonins or ligands in order to improve the attachment of liposomes to unhealthy tissue or to activate events such as, but not limited to, endocytosis. Liposomes may contain a low or a high pH in order to improve the delivery of the pharmaceutical formulations.


The formation of liposomes may depend on the physicochemical characteristics such as, but not limited to, the pharmaceutical formulation entrapped and the liposomal ingredients, the nature of the medium in which the lipid vesicles are dispersed, the effective concentration of the entrapped substance and its potential toxicity, any additional processes involved during the application and/or delivery of the vesicles, the optimization size, polydispersity and the shelf-life of the vesicles for the intended application, and the batch-to-batch reproducibility and possibility of large-scale production of safe and efficient liposomal products.


In some embodiments, pharmaceutical compositions described herein may include, without limitation, liposomes such as those formed from 1,2-dioleyloxy-N,N-dimethylaminopropane (DODMA) liposomes, DiLa2 liposomes from Marina Biotech (Bothell, WA), 1,2-dilinoleyloxy-3-dimethylaminopropane (DLin-DMA), 2,2-dilinoleyl-4-(2-dimethylaminoethyl)-[1,3]-dioxolane (DLin-KC2-DMA), and MC3 (US20100324120; herein incorporated by reference in its entirety) and liposomes which may deliver small molecule drugs such as, but not limited to, DOXIL® from Janssen Biotech, Inc. (Horsham, PA).


In some embodiments, pharmaceutical compositions described herein may include, without limitation, liposomes such as those formed from the synthesis of stabilized plasmid-lipid particles (SPLP) or stabilized nucleic acid lipid particle (SNALP) that have been previously described and shown to be suitable for oligonucleotide delivery in vitro and in vivo (see Wheeler et al. Gene Therapy. 1999 6:271-281; Zhang et al. Gene Therapy. 1999 6:1438-1447; Jeffs et al. Pharm Res. 2005 22:362-372; Morrissey et al., Nat Biotechnol. 2005 2:1002-1007; Zimmermann et al., Nature. 2006 441:111-114; Heyes et al. J Contr Rel. 2005 107:276-287; Semple et al. Nature Biotech. 2010 28:172-176; Judge et al. J Clin Invest. 2009 119:661-673; deFougerolles Hum Gene Ther. 2008 19:125-132; U.S. Patent Publication No US20130122104; all of which are incorporated herein in their entireties). The original manufacture method by Wheeler et al. was a detergent dialysis method, which was later improved by Jeffs et al. and is referred to as the spontaneous vesicle formation method. The liposome formulations are composed of 3 to 4 lipid components in addition to the polynucleotide. As an example a liposome can contain, but is not limited to, 55% cholesterol, 20% disteroylphosphatidyl choline (DSPC), 10% PEG-S-DSG, and 15% 1,2-dioleyloxy-N,N-dimethylaminopropane (DODMA), as described by Jeffs et al. As another example, certain liposome formulations may contain, but are not limited to, 48% cholesterol, 20% DSPC, 2% PEG-c-DMA, and 30% cationic lipid, where the cationic lipid can be 1,2-distearloxy-N,N-dimethylaminopropane (DSDMA), DODMA, DLin-DMA, or 1,2-dilinolenyloxy-3-dimethylaminopropane (DLenDMA), as described by Heyes et al.


In some embodiments, liposome formulations may comprise from about 25.0% cholesterol to about 40.0% cholesterol, from about 30.0% cholesterol to about 45.0% cholesterol, from about 35.0% cholesterol to about 50.0% cholesterol and/or from about 48.5% cholesterol to about 60% cholesterol. In some embodiments, formulations may comprise a percentage of cholesterol selected from the group consisting of 28.5%, 31.5%, 33.5%, 36.5%, 37.0%, 38.5%, 39.0% and 43.5%. In some embodiments, formulations may comprise from about 5.0% to about 10.0% DSPC and/or from about 7.0% to about 15.0% DSPC.


In some embodiments, the RNA (e.g., mRNA) vaccine pharmaceutical compositions may be formulated in liposomes such as, but not limited to, DiLa2 liposomes (Marina Biotech, Bothell, WA), SMARTICLES® (Marina Biotech, Bothell, WA), neutral DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) based liposomes (e.g., siRNA delivery for ovarian cancer (Landen et al. Cancer Biology & Therapy 2006 5(12)1708-1713); herein incorporated by reference in its entirety) and hyaluronan-coated liposomes (Quiet Therapeutics, Israel).


In some embodiments, the cationic lipid may be a low molecular weight cationic lipid such as those described in U.S. Patent Application No. 2013/0090372, the contents of which are herein incorporated by reference in their entirety.


In some embodiments, the RNA (e.g., mRNA) vaccines may be formulated in a lipid vesicle, which may have crosslinks between functionalized lipid bilayers.


In some embodiments, the RNA (e.g., mRNA) vaccines may be formulated in a lipid-polycation complex. The formation of the lipid-polycation complex may be accomplished by methods known in the art and/or as described in U.S. Pub. No. 2012/0178702, herein incorporated by reference in its entirety. As a non-limiting example, the polycation may include a cationic peptide or a polypeptide such as, but not limited to, polylysine, polyornithine and/or polyarginine. In some embodiments, the RNA (e.g., mRNA) vaccines may be formulated in a lipid-polycation complex, which may further include a non-cationic lipid such as, but not limited to, cholesterol or dioleoyl phosphatidylethanolamine (DOPE).


In some embodiments, the ratio of PEG in the lipid nanoparticle (LNP) formulations may be increased or decreased and/or the carbon chain length of the PEG lipid may be modified from C14 to C18 to alter the pharmacokinetics and/or biodistribution of the LNP formulations. As a non-limiting example, LNP formulations may contain from about 0.5% to about 3.0%, from about 1.0% to about 3.5%, from about 1.5% to about 4.0%, from about 2.0% to about 4.5%, from about 2.5% to about 5.0% and/or from about 3.0% to about 6.0% of the lipid molar ratio of PEG-c-DOMG (R-3-[(ω-methoxy-poly(ethyleneglycol)2000)carbamoyl)]-1,2-dimyristyloxypropyl-3-amine) (also referred to herein as PEG-DOMG) as compared to the cationic lipid, DSPC and cholesterol. In some embodiments, the PEG-c-DOMG may be replaced with a PEG lipid such as, but not limited to, PEG-DSG (1,2-Distearoyl-sn-glycerol, methoxypolyethylene glycol), PEG-DMG (1,2-Dimyristoyl-sn-glycerol) and/or PEG-DPG (1,2-Dipalmitoyl-sn-glycerol, methoxypolyethylene glycol). The cationic lipid may be selected from any lipid known in the art such as, but not limited to, DLin-MC3-DMA, DLin-DMA, C12-200 and DLin-KC2-DMA.


In some embodiments, the RNA (e.g., mRNA) vaccines may be formulated in a lipid nanoparticle.


In some embodiments, the RNA (e.g., mRNA) vaccine formulation comprising the polynucleotide is a nanoparticle which may comprise at least one lipid. The lipid may be selected from, but is not limited to, DLin-DMA, DLin-K-DMA, 98N12-5, C12-200, DLin-MC3-DMA, DLin-KC2-DMA, DODMA, PLGA, PEG, PEG-DMG, PEGylated lipids and amino alcohol lipids. In another aspect, the lipid may be a cationic lipid such as, but not limited to, DLin-DMA, DLin-D-DMA, DLin-MC3-DMA, DLin-KC2-DMA, DODMA and amino alcohol lipids. The amino alcohol cationic lipid may be the lipids described in and/or made by the methods described in U.S. Patent Publication No. US20130150625, herein incorporated by reference in its entirety. As a non-limiting example, the cationic lipid may be 2-amino-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-{[(9Z,2Z)-octadeca-9,12-dien-1-yloxy]methyl}propan-1-ol (Compound 1 in US2013/0150625); 2-amino-3-[(9Z)-octadec-9-en-1-yloxy]-2-{[(9Z)-octadec-9-en-1-yloxy]methyl}propan-1-ol (Compound 2 in US2013/0150625); 2-amino-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-[(octyloxy)methyl]propan-1-ol (Compound 3 in US2013/0150625); and 2-(dimethylamino)-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-{[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]methyl}propan-1-ol (Compound 4 in US2013/0150625); or any pharmaceutically acceptable salt or stereoisomer thereof.


Lipid nanoparticle formulations typically comprise a lipid, in particular, an ionizable cationic lipid, for example, 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), or di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, and further comprise a neutral lipid, a sterol and a molecule capable of reducing particle aggregation, for example a PEG or PEG-modified lipid.


In some embodiments, the lipid nanoparticle formulation consists essentially of (i) at least one lipid selected from the group consisting of 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate; (ii) a neutral lipid selected from DSPC, DPPC, POPC, DOPE and SM; (iii) a sterol, e.g., cholesterol; and (iv) a PEG-lipid, e.g., PEG-DMG or PEG-cDMA, in a molar ratio of about 20-60% cationic lipid:5-25% neutral lipid: 25-55% sterol; 0.5-15% PEG-lipid.


In some embodiments, the formulation includes from about 25% to about 75% on a molar basis of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, e.g., from about 35 to about 65%, from about 45 to about 65%, about 60%, about 57.5%, about 50% or about 40% on a molar basis.


In some embodiments, the formulation includes from about 0.5% to about 15% on a molar basis of the neutral lipid e.g., from about 3 to about 12%, from about 5 to about 10% or about 15%, about 10%, or about 7.5% on a molar basis. Examples of neutral lipids include, but are not limited to, DSPC, POPC, DPPC, DOPE and SM. In some embodiments, the formulation includes from about 5% to about 50% on a molar basis of the sterol (e.g., about 15 to about 45%, about 20 to about 40%, about 40%, about 38.5%, about 35%, or about 31% on a molar basis. An exemplary sterol is cholesterol. In some embodiments, the formulation includes from about 0.5% to about 20% on a molar basis of the PEG or PEG-modified lipid (e.g., about 0.5 to about 10%, about 0.5 to about 5%, about 1.5%, about 0.5%, about 1.5%, about 3.5%, or about 5% on a molar basis. In some embodiments, the PEG or PEG modified lipid comprises a PEG molecule of an average molecular weight of 2,000 Da. In other embodiments, the PEG or PEG modified lipid comprises a PEG molecule of an average molecular weight of less than 2,000, for example around 1,500 Da, around 1,000 Da, or around 500 Da. Examples of PEG-modified lipids include, but are not limited to, PEG-distearoyl glycerol (PEG-DMG) (also referred herein as PEG-C14 or C14-PEG), PEG-cDMA (further discussed in Reyes et al. J. Controlled Release, 107, 276-287 (2005) the contents of which are herein incorporated by reference in their entirety).


In some embodiments, the formulations of the present disclosure include 25-75% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 0.5-15% of the neutral lipid, 5-50% of the sterol, and 0.5-20% of the PEG or PEG-modified lipid on a molar basis.


In some embodiments, the formulations of the present disclosure include 35-65% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 3-12% of the neutral lipid, 15-45% of the sterol, and 0.5-10% of the PEG or PEG-modified lipid on a molar basis.


In some embodiments, the formulations of the present disclosure include 45-65% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 5-10% of the neutral lipid, 25-40% of the sterol, and 0.5-10% of the PEG or PEG-modified lipid on a molar basis. In some embodiments, the formulations of the present disclosure include about 60% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, about 7.5% of the neutral lipid, about 31% of the sterol, and about 1.5% of the PEG or PEG-modified lipid on a molar basis.


In some embodiments, the formulations of the present disclosure include about 50% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, about 10% of the neutral lipid, about 38.5% of the sterol, and about 1.5% of the PEG or PEG-modified lipid on a molar basis.


In some embodiments, the formulations of the present disclosure include about 50% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, about 10% of the neutral lipid, about 35% of the sterol, about 4.5% or about 5% of the PEG or PEG-modified lipid, and about 0.5% of the targeting lipid on a molar basis.


In some embodiments, the formulations of the present disclosure include about 40% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, about 15% of the neutral lipid, about 40% of the sterol, and about 5% of the PEG or PEG-modified lipid on a molar basis.


In some embodiments, the formulations of the present disclosure include about 57.2% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, about 7.1% of the neutral lipid, about 34.3% of the sterol, and about 1.4% of the PEG or PEG-modified lipid on a molar basis.


In some embodiments, the formulations of the present disclosure include about 57.5% of a cationic lipid selected from the PEG lipid is PEG-cDMA (PEG-cDMA is further discussed in Reyes et al. (J. Controlled Release, 107, 276-287 (2005), the contents of which are herein incorporated by reference in their entirety), about 7.5% of the neutral lipid, about 31.5% of the sterol, and about 3.5% of the PEG or PEG-modified lipid on a molar basis. In some embodiments, lipid nanoparticle formulation consists essentially of a lipid mixture in molar ratios of about 20-70% cationic lipid: 5-45% neutral lipid: 20-55% cholesterol: 0.5-15% PEG-modified lipid; more preferably in a molar ratio of about 20-60% cationic lipid:5-25% neutral lipid: 25-55% cholesterol: 0.5-15% PEG-modified lipid.


In some embodiments, the molar lipid ratio is approximately 50/10/38.5/1.5 (mol % cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG, PEG-DSG or PEG-DPG), 57.2/7.1134.3/1.4 (mol % cationic lipid/neutral lipid, e.g., DPPC/Chol/PEG-modified lipid, e.g., PEG-cDMA), 40/15/40/5 (mol % cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG), 50/10/35/4.5/0.5 (mol % cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DSG), 50/10/35/5 (cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG), 40/10/40/10 (mol % cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG or PEG-cDMA), 35/15/40/10 (mol % cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG or PEG-cDMA) or 52/13/30/5 (mol % cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG or PEG-cDMA).


Examples of lipid nanoparticle compositions and methods of making same are described, for example, in Semple et al. (2010) Nat. Biotechnol. 28:172-176; Jayarama et al. (2012), Angew. Chem. Int. Ed., 51: 8529-8533; and Maier et al. (2013) Molecular Therapy 21, 1570-1578 (the contents of each of which are incorporated herein by reference in their entirety).


In some embodiments, the lipid nanoparticle formulations described herein may comprise a cationic lipid, a PEG lipid and a structural lipid and optionally comprise a non-cationic lipid. As a non-limiting example, the lipid nanoparticle may comprise about 40-60% of cationic lipid, about 5-15% of a non-cationic lipid, about 1-2% of a PEG lipid and about 30-50% of a structural lipid. As another non-limiting example, the lipid nanoparticle may comprise about 50% cationic lipid, about 10% non-cationic lipid, about 1.5% PEG lipid and about 38.5% structural lipid. As yet another non-limiting example, the lipid nanoparticle may comprise about 55% cationic lipid, about 10% non-cationic lipid, about 2.5% PEG lipid and about 32.5% structural lipid. In some embodiments, the cationic lipid may be any cationic lipid described herein such as, but not limited to, DLin-KC2-DMA, DLin-MC3-DMA and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate.


In some embodiments, the lipid nanoparticle formulations described herein may be 4 component lipid nanoparticles. The lipid nanoparticle may comprise a cationic lipid, a non-cationic lipid, a PEG lipid and a structural lipid. As a non-limiting example, the lipid nanoparticle may comprise about 40-60% of cationic lipid, about 5-15% of a non-cationic lipid, about 1-2% of a PEG lipid and about 30-50% of a structural lipid. As another non-limiting example, the lipid nanoparticle may comprise about 50% cationic lipid, about 10% non-cationic lipid, about 1.5% PEG lipid and about 38.5% structural lipid. As yet another non-limiting example, the lipid nanoparticle may comprise about 55% cationic lipid, about 10% non-cationic lipid, about 2.5% PEG lipid and about 32.5% structural lipid. In some embodiments, the cationic lipid may be any cationic lipid described herein such as, but not limited to, DLin-KC2-DMA, DLin-MC3-DMA and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate.


In some embodiments, the lipid nanoparticle formulations described herein may comprise a cationic lipid, a non-cationic lipid, a PEG lipid and a structural lipid. As a non-limiting example, the lipid nanoparticle comprise about 50% of the cationic lipid DLin-KC2-DMA, about 10% of the non-cationic lipid DSPC, about 1.5% of the PEG lipid PEG-DOMG and about 38.5% of the structural lipid cholesterol. As a non-limiting example, the lipid nanoparticle comprise about 50% of the cationic lipid DLin-MC3-DMA, about 10% of the non-cationic lipid DSPC, about 1.5% of the PEG lipid PEG-DOMG and about 38.5% of the structural lipid cholesterol. As a non-limiting example, the lipid nanoparticle comprise about 50% of the cationic lipid DLin-MC3-DMA, about 10% of the non-cationic lipid DSPC, about 1.5% of the PEG lipid PEG-DMG and about 38.5% of the structural lipid cholesterol. As yet another non-limiting example, the lipid nanoparticle comprise about 55% of the cationic lipid di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, about 10% of the non-cationic lipid DSPC, about 2.5% of the PEG lipid PEG-DMG and about 32.5% of the structural lipid cholesterol.


As a non-limiting example, the cationic lipid may be selected from (20Z,23Z)-N,N-dimethylnonacosa-20,23-dien-10-amine, (17Z,20Z)-N,N-dimemylhexacosa-17,20-dien-9-amine, (1Z,19Z)-N5N-dimethylpentacosa-1 6, 19-dien-8-amine, (13Z,16Z)-N,N-dimethyldocosa-13,16-dien-5-amine, (12Z,15Z)-N,N-dimethylhenicosa-12,15-dien-4-amine, (14Z,17Z)-N,N-dimethyltricosa-14,17-dien-6-amine, (15Z,18Z)-N,N-dimethyltetracosa-15,18-dien-7-amine, (18Z,21Z)-N,N-dimethylheptacosa-18,21-dien-10-amine, (15Z,18Z)-N,N-dimethyltetracosa-15,18-dien-5-amine, (14Z,17Z)-N,N-dimethyltricosa-14,17-dien-4-amine, (19Z,22Z)-N,N-dimeihyloctacosa-19,22-dien-9-amine, (18Z, 21 Z)-N,N-dimethylheptacosa-18,21-dien-8-amine, (17Z,20Z)-N,N-dimethylhexacosa-17,20-dien-7-amine, (16Z,19Z)-N,N-dimethylpentacosa-16,19-dien-6-amine, (22Z,25Z)-N,N-dimethylhentriaconta-22,25-dien-10-amine, (21 Z,24Z)-N,N-dimethyltriaconta-21,24-dien-9-amine, (18Z)-N,N-dimetylheptacos-18-en-10-amine, (17Z)-N,N-dimethylhexacos-17-en-9-amine, (19Z,22Z)-N,N-dimethyloctacosa-19,22-dien-7-amine, N,N-dimethylheptacosan-10-amine, (20Z,23Z)-N-ethyl-N-methylnonacosa-20,23-dien-10-amine, 1-[(11Z,14Z)-1-nonylicosa-11,14-dien-1-yl] pyrrolidine, (20Z)-N,N-dimethylheptacos-20-en-1 O-amine, (15Z)-N,N-dimethyl eptacos-15-en-10-amine, (14Z)-N,N-dimethylnonacos-14-en-10-amine, (17Z)-N,N-dimethylnonacos-17-en-10-amine, (24Z)-N,N-dimethyltritriacont-24-en-10-amine, (20Z)-N,N-dimethylnonacos-20-en-1 O-amine, (22Z)-N,N-dimethylhentriacont-22-en-10-amine, (16Z)-N,N-dimethylpentacos-16-en-8-amine, (12Z,15Z)-N,N-dimethyl-2-nonylhenicosa-12,15-dien-1-amine, (13Z,16Z)-N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine, N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl] eptadecan-8-amine, 1-[(1S,2R)-2-hexylcyclopropyl]-N,N-dimethylnonadecan-10-amine, N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]nonadecan-10-amine, N,N-dimethyl-21-[(1S,2R)-2-octylcyclopropyl]henicosan-10-amine,N,N-dimethyl-1-[(1S,2S)-2-{[(1R,2R)-2-pentylcyclopropyl]methyl}cyclopropyl]nonadecan-10-amine,N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]hexadecan-8-amine, N,N-dimethyl-[(1R,2S)-2-undecylcyclopropyl]tetradecan-5-amine, N,N-dimethyl-3-17-[(1S,2R)-2-octylcyclopropyl]heptyl} dodecan-1-amine, 1-[(1R,2S)-2-hepty lcyclopropyl]-N,N-dimethyloctadecan-9-amine, 1-[(1S,2R)-2-decylcyclopropyl]-N,N-dimethylpentadecan-6-amine, N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]pentadecan-8-amine, R-N,N-dimethyl-1-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-3-(octyloxy)propan-2-amine, S-N,N-dimethyl-1-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-3-(octyloxy)propan-2-amine, 1-12-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-1-[(octyloxy)methyl]ethylIpyrrolidine, (2S)-N,N-dimethyl-1-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-3-[(5Z)-oct-5-en-1-yloxy]propan-2-amine, 1-12-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-1-[(octyloxy)methyl]ethylIazetidine, (2S)-1-(hexyloxy)-N,N-dimethyl-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]propan-2-amine, (2S)-1-(heptyloxy)-N,N-dimethyl-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]propan-2-amine, N,N-dimethyl-1-(nonyloxy)-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]propan-2-amine, N,N-dimethyl-1-[(9Z)-octadec-9-en-1-yloxy]-3-(octyloxy)propan-2-amine; (2S)-N,N-dimethyl-1-[(6Z,9Z,12Z)-octadeca-6,9,12-trien-1-yloxy]-3-(octyloxy)propan-2-amine, (2S)-1-[(11Z,14Z)-icosa-11,14-dien-1-yloxy]-N,N-dimethyl-3-(pentyloxy)propan-2-amine, (2S)-1-(hexyloxy)-3-[(11Z,14Z)-icosa-11,14-dien-1-yloxy]-N,N-dimethylpropan-2-amine, 1-[(11Z,14Z)-icosa-11,14-dien-1-yloxy]-N,N-dimethyl-3-(octyloxy)propan-2-amine, 1-[(13Z,16Z)-docosa-13,16-dien-1-yloxy]-N,N-dimethyl-3-(octyloxy)propan-2-amine, (2S)-1-[(13Z,16Z)-docosa-13,16-dien-1-yloxy]-3-(hexyloxy)-N,N-dimethylpropan-2-amine, (2S)-1-[(13Z)-docos-13-en-1-yloxy]-3-(hexyloxy)-N,N-dimethylpropan-2-amine, 1-[(13Z)-docos-13-en-1-yloxy]-N,N-dimethyl-3-(octyloxy)propan-2-amine, 1-[(9Z)-hexadec-9-en-1-yloxy]-N,N-dimethyl-3-(octyloxy)propan-2-amine, (2R)-N,N-dimethyl-H(1-metoylo ctyl)oxy]-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]propan-2-amine, (2R)-1-[(3,7-dimethyloctyl)oxy]-N,N-dimethyl-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]propan-2-amine, N,N-dimethyl-1-(octyloxy)-3-({8-[(1S,2S)-2-{[(1R,2R)-2-pentylcyclopropyl]methyl}cyclopropyl]octyl}oxy)propan-2-amine, N,N-dimethyl-1-{[8-(2-oclylcyclopropyl)octyl]oxy}-3-(octyloxy)propan-2-amine and (11E,20Z,23Z)-N,N-dimethylnonacosa-11,20,2-trien-10-amine or a pharmaceutically acceptable salt or stereoisomer thereof.


In some embodiments, the LNP formulations of the RNA (e.g., mRNA) vaccines may contain PEG-c-DOMG at 3% lipid molar ratio. In some embodiments, the LNP formulations of the RNA (e.g., mRNA) vaccines may contain PEG-c-DOMG at 1.5% lipid molar ratio.


In some embodiments, the pharmaceutical compositions of the RNA (e.g., mRNA) vaccines may include at least one of the PEGylated lipids described in International Publication No. WO2012/099755, the contents of which are herein incorporated by reference in their entirety.


In some embodiments, the LNP formulation may contain PEG-DMG 2000 (1,2-dimyristoyl-sn-glycero-3-phophoethanolamine-N-[methoxy(polyethylene glycol)-2000). In some embodiments, the LNP formulation may contain PEG-DMG 2000, a cationic lipid known in the art and at least one other component. In some embodiments, the LNP formulation may contain PEG-DMG 2000, a cationic lipid known in the art, DSPC and cholesterol. As a non-limiting example, the LNP formulation may contain PEG-DMG 2000, DLin-DMA, DSPC and cholesterol. As another non-limiting example the LNP formulation may contain PEG-DMG 2000, DLin-DMA, DSPC and cholesterol in a molar ratio of 2:40:10:48 (see e.g., Geall et al., Nonviral delivery of self-amplifying RNA (e.g., mRNA) vaccines, PNAS 2012; PMID: 22908294, the contents of each of which are herein incorporated by reference in their entirety).


The lipid nanoparticles described herein may be made in a sterile environment.


In some embodiments, the LNP formulation may be formulated in a nanoparticle such as a nucleic acid-lipid particle. As a non-limiting example, the lipid particle may comprise one or more active agents or therapeutic agents; one or more cationic lipids comprising from about 50 mol % to about 85 mol % of the total lipid present in the particle; one or more non-cationic lipids comprising from about 13 mol % to about 49.5 mol % of the total lipid present in the particle; and one or more conjugated lipids that inhibit aggregation of particles comprising from about 0.5 mol % to about 2 mol % of the total lipid present in the particle.


The nanoparticle formulations may comprise a phosphate conjugate. The phosphate conjugate may increase in vivo circulation times and/or increase the targeted delivery of the nanoparticle. As a non-limiting example, the phosphate conjugates may include a compound of any one of the formulas described in International Application No. WO2013/033438, the contents of which are herein incorporated by reference in its entirety.


The nanoparticle formulation may comprise a polymer conjugate. The polymer conjugate may be a water soluble conjugate. The polymer conjugate may have a structure as described in U.S. Patent Application No. 2013/0059360, the contents of which are herein incorporated by reference in its entirety. In some embodiments, polymer conjugates with the polynucleotides of the present disclosure may be made using the methods and/or segmented polymeric reagents described in U.S. Patent Application No. 2013/0072709, the contents of which are herein incorporated by reference in its entirety. In some embodiments, the polymer conjugate may have pendant side groups comprising ring moieties such as, but not limited to, the polymer conjugates described in U.S. Patent Publication No. US2013/0196948, the contents which are herein incorporated by reference in its entirety.


The nanoparticle formulations may comprise a conjugate to enhance the delivery of nanoparticles of the present disclosure in a subject. Further, the conjugate may inhibit phagocytic clearance of the nanoparticles in a subject. In one aspect, the conjugate may be a “self” peptide designed from the human membrane protein CD47 (e.g., the “self” particles described by Rodriguez et al. (Science 2013 339, 971-975), herein incorporated by reference in its entirety). As shown by Rodriguez et al., the self peptides delayed macrophage-mediated clearance of nanoparticles which enhanced delivery of the nanoparticles. In another aspect, the conjugate may be the membrane protein CD47 (e.g., see Rodriguez et al. Science 2013 339, 971-975, herein incorporated by reference in its entirety). Rodriguez et al. showed that, similarly to “self” peptides, CD47 can increase the circulating particle ratio in a subject as compared to scrambled peptides and PEG coated nanoparticles.


In some embodiments, the RNA (e.g., mRNA) vaccines of the present disclosure are formulated in nanoparticles which comprise a conjugate to enhance the delivery of the nanoparticles of the present disclosure in a subject. The conjugate may be the CD47 membrane or the conjugate may be derived from the CD47 membrane protein, such as the “self” peptide described previously. In some embodiments, the nanoparticle may comprise PEG and a conjugate of CD47 or a derivative thereof. In some embodiments, the nanoparticle may comprise both the “self” peptide described above and the membrane protein CD47.


In some embodiments, a “self” peptide and/or CD47 protein may be conjugated to a virus-like particle or pseudovirion, as described herein for delivery of the RNA (e.g., mRNA) vaccines of the present disclosure.


In some embodiments, RNA (e.g., mRNA) vaccine pharmaceutical compositions comprising the polynucleotides of the present disclosure and a conjugate that may have a degradable linkage. Non-limiting examples of conjugates include an aromatic moiety comprising an ionizable hydrogen atom, a spacer moiety, and a water-soluble polymer. As a non-limiting example, pharmaceutical compositions comprising a conjugate with a degradable linkage and methods for delivering such pharmaceutical compositions are described in U.S. Patent Publication No. US2013/0184443, the contents of which are herein incorporated by reference in their entirety.


The nanoparticle formulations may be a carbohydrate nanoparticle comprising a carbohydrate carrier and a RNA (e.g., mRNA) vaccine. As a non-limiting example, the carbohydrate carrier may include, but is not limited to, an anhydride-modified phytoglycogen or glycogen-type material, phytoglycogen octenyl succinate, phytoglycogen beta-dextrin, anhydride-modified phytoglycogen beta-dextrin. (See e.g., International Publication No. WO2012/109121; the contents of which are herein incorporated by reference in their entirety).


Nanoparticle formulations of the present disclosure may be coated with a surfactant or polymer in order to improve the delivery of the particle. In some embodiments, the nanoparticle may be coated with a hydrophilic coating such as, but not limited to, PEG coatings and/or coatings that have a neutral surface charge. The hydrophilic coatings may help to deliver nanoparticles with larger payloads such as, but not limited to, RNA (e.g., mRNA) vaccines within the central nervous system. As a non-limiting example nanoparticles comprising a hydrophilic coating and methods of making such nanoparticles are described in U.S. Patent Publication No. US2013/0183244, the contents of which are herein incorporated by reference in their entirety.


In some embodiments, the lipid nanoparticles of the present disclosure may be hydrophilic polymer particles. Non-limiting examples of hydrophilic polymer particles and methods of making hydrophilic polymer particles are described in U.S. Patent Publication No. US2013/0210991, the contents of which are herein incorporated by reference in their entirety.


In some embodiments, the lipid nanoparticles of the present disclosure may be hydrophobic polymer particles.


Lipid nanoparticle formulations may be improved by replacing the cationic lipid with a biodegradable cationic lipid which is known as a rapidly eliminated lipid nanoparticle (reLNP). Ionizable cationic lipids, such as, but not limited to, DLinDMA, DLin-KC2-DMA, and DLin-MC3-DMA, have been shown to accumulate in plasma and tissues over time and may be a potential source of toxicity. The rapid metabolism of the rapidly eliminated lipids can improve the tolerability and therapeutic index of the lipid nanoparticles by an order of magnitude from a 1 mg/kg dose to a 10 mg/kg dose in rat. Inclusion of an enzymatically degraded ester linkage can improve the degradation and metabolism profile of the cationic component, while still maintaining the activity of the reLNP formulation. The ester linkage can be internally located within the lipid chain or it may be terminally located at the terminal end of the lipid chain. The internal ester linkage may replace any carbon in the lipid chain.


In some embodiments, the internal ester linkage may be located on either side of the saturated carbon.


In some embodiments, an immune response may be elicited by delivering a lipid nanoparticle which may include a nanospecies, a polymer and an immunogen. (U.S. Publication No. 2012/0189700 and International Publication No. WO2012/099805; each of which is herein incorporated by reference in their entirety). The polymer may encapsulate the nanospecies or partially encapsulate the nanospecies. The immunogen may be a recombinant protein, a modified RNA and/or a polynucleotide described herein. In some embodiments, the lipid nanoparticle may be formulated for use in a vaccine such as, but not limited to, against a pathogen.


Lipid nanoparticles may be engineered to alter the surface properties of particles so the lipid nanoparticles may penetrate the mucosal barrier. Mucus is located on mucosal tissue such as, but not limited to, oral (e.g., the buccal and esophageal membranes and tonsil tissue), ophthalmic, gastrointestinal (e.g., stomach, small intestine, large intestine, colon, rectum), nasal, respiratory (e.g., nasal, pharyngeal, tracheal and bronchial membranes), genital (e.g., vaginal, cervical and urethral membranes). Nanoparticles larger than 10-200 nm which are preferred for higher drug encapsulation efficiency and the ability to provide the sustained delivery of a wide array of drugs have been thought to be too large to rapidly diffuse through mucosal barriers. Mucus is continuously secreted, shed, discarded or digested and recycled so most of the trapped particles may be removed from the mucosa tissue within seconds or within a few hours. Large polymeric nanoparticles (200 nm-500 nm in diameter) which have been coated densely with a low molecular weight polyethylene glycol (PEG) diffused through mucus only 4 to 6-fold lower than the same particles diffusing in water (Lai et al. PNAS 2007 104:1482-487; Lai et al. Adv Drug Deliv Rev. 2009 61: 158-171; each of which is herein incorporated by reference in their entirety). The transport of nanoparticles may be determined using rates of permeation and/or fluorescent microscopy techniques including, but not limited to, fluorescence recovery after photobleaching (FRAP) and high resolution multiple particle tracking (MPT). As a non-limiting example, compositions which can penetrate a mucosal barrier may be made as described in U.S. Pat. No. 8,241,670 or International Patent Publication No. WO2013/110028, the contents of each of which are herein incorporated by reference in its entirety.


The lipid nanoparticle engineered to penetrate mucus may comprise a polymeric material (i.e. a polymeric core) and/or a polymer-vitamin conjugate and/or a tri-block co-polymer. The polymeric material may include, but is not limited to, polyamines, polyethers, polyamides, polyesters, polycarbamates, polyureas, polycarbonates, poly(styrenes), polyimides, polysulfones, polyurethanes, polyacetylenes, polyethylenes, polyethyeneimines, polyisocyanates, polyacrylates, polymethacrylates, polyacrylonitriles, and polyarylates. The polymeric material may be biodegradable and/or biocompatible. Non-limiting examples of biocompatible polymers are described in International Patent Publication No. WO2013/116804, the contents of which are herein incorporated by reference in their entirety. The polymeric material may additionally be irradiated. As a non-limiting example, the polymeric material may be gamma irradiated (see e.g., International App. No. WO2012/082165, herein incorporated by reference in its entirety). Non-limiting examples of specific polymers include poly(caprolactone) (PCL), ethylene vinyl acetate polymer (EVA), poly(lactic acid) (PLA), poly(L-lactic acid) (PLLA), poly(glycolic acid) (PGA), poly(lactic acid-co-glycolic acid) (PLGA), poly(L-lactic acid-co-glycolic acid) (PLLGA), poly(D,L-lactide) (PDLA), poly(L-lactide) (PLLA), poly(D,L-lactide-co-caprolactone), poly(D,L-lactide-co-caprolactone-co-glycolide), poly(D,L-lactide-co-PEO-co-D,L-lactide), poly(D,L-lactide-co-PPO-co-D,L-lactide), polyalkyl cyanoacralate, polyurethane, poly-L-lysine (PLL), hydroxypropyl methacrylate (HPMA), polyethyleneglycol, poly-L-glutamic acid, poly(hydroxy acids), polyanhydrides, polyorthoesters, poly(ester amides), polyamides, poly(ester ethers), polycarbonates, polyalkylenes such as polyethylene and polypropylene, polyalkylene glycols such as poly(ethylene glycol) (PEG), polyalkylene oxides (PEO), polyalkylene terephthalates such as poly(ethylene terephthalate), polyvinyl alcohols (PVA), polyvinyl ethers, polyvinyl esters such as poly(vinyl acetate), polyvinyl halides such as poly(vinyl chloride) (PVC), polyvinylpyrrolidone, polysiloxanes, polystyrene (PS), polyurethanes, derivatized celluloses such as alkyl celluloses, hydroxyalkyl celluloses, cellulose ethers, cellulose esters, nitro celluloses, hydroxypropylcellulose, carboxymethylcellulose, polymers of acrylic acids, such as poly(methyl(meth)acrylate) (PMMA), poly(ethyl(meth)acrylate), poly(butyl(meth)acrylate), poly(isobutyl(meth)acrylate), poly(hexyl(meth)acrylate), poly(isodecyl(meth)acrylate), poly(lauryl(meth)acrylate), poly(phenyl(meth)acrylate), poly(methyl acrylate), poly(isopropyl acrylate), poly(isobutyl acrylate), poly(octadecyl acrylate) and copolymers and mixtures thereof, polydioxanone and its copolymers, polyhydroxyalkanoates, polypropylene fumarate, polyoxymethylene, poloxamers, poly(ortho)esters, poly(butyric acid), poly(valeric acid), poly(lactide-co-caprolactone), PEG-PLGA-PEG and trimethylene carbonate, polyvinylpyrrolidone.The lipid nanoparticle may be coated or associated with a co-polymer such as, but not limited to, a block co-polymer (such as a branched polyether-polyamide block copolymer described in International Publication No. WO2013/012476, herein incorporated by reference in its entirety), and (poly(ethylene glycol))-(poly(propylene oxide))-(poly(ethylene glycol)) triblock copolymer (see e.g., U.S. Publication 2012/0121718 and U.S. Publication 2010/0003337 and U.S. Pat. No. 8,263,665, the contents of each of which is herein incorporated by reference in their entirety). The co-polymer may be a polymer that is generally regarded as safe (GRAS) and the formation of the lipid nanoparticle may be in such a way that no new chemical entities are created. For example, the lipid nanoparticle may comprise poloxamers coating PLGA nanoparticles without forming new chemical entities which are still able to rapidly penetrate human mucus (Yang et al. Angew. Chem. Int. Ed. 2011 50:2597-2600; the contents of which are herein incorporated by reference in their entirety). A non-limiting scalable method to produce nanoparticles which can penetrate human mucus is described by Xu et al. (see, e.g., J Control Release 2013, 170:279-86; the contents of which are herein incorporated by reference in their entirety).


The vitamin of the polymer-vitamin conjugate may be vitamin E. The vitamin portion of the conjugate may be substituted with other suitable components such as, but not limited to, vitamin A, vitamin E, other vitamins, cholesterol, a hydrophobic moiety, or a hydrophobic component of other surfactants (e.g., sterol chains, fatty acids, hydrocarbon chains and alkylene oxide chains).


The lipid nanoparticle engineered to penetrate mucus may include surface altering agents such as, but not limited to, polynucleotides, anionic proteins (e.g., bovine serum albumin), surfactants (e.g., cationic surfactants such as for example dimethyldioctadecyl-ammonium bromide), sugars or sugar derivatives (e.g., cyclodextrin), nucleic acids, polymers (e.g., heparin, polyethylene glycol and poloxamer), mucolytic agents (e.g., N-acetylcysteine, mugwort, bromelain, papain, clerodendrum, acetylcysteine, bromhexine, carbocisteine, eprazinone, mesna, ambroxol, sobrerol, domiodol, letosteine, stepronin, tiopronin, gelsolin, thymosin β4 dornase alfa, neltenexine, erdosteine) and various DNases including rhDNase.


The surface altering agent may be embedded or enmeshed in the particle's surface or disposed (e.g., by coating, adsorption, covalent linkage, or other process) on the surface of the lipid nanoparticle. (see e.g., U.S. Publication 2010/0215580 and U.S. Publication 2008/0166414 and US2013/0164343; the contents of each of which are herein incorporated by reference in their entirety).


In some embodiments, the mucus penetrating lipid nanoparticles may comprise at least one polynucleotide described herein. The polynucleotide may be encapsulated in the lipid nanoparticle and/or disposed on the surface of the particle. The polynucleotide may be covalently coupled to the lipid nanoparticle. Formulations of mucus penetrating lipid nanoparticles may comprise a plurality of nanoparticles. Further, the formulations may contain particles which may interact with the mucus and alter the structural and/or adhesive properties of the surrounding mucus to decrease mucoadhesion, which may increase the delivery of the mucus penetrating lipid nanoparticles to the mucosal tissue.


In some embodiments, the mucus penetrating lipid nanoparticles may be a hypotonic formulation comprising a mucosal penetration enhancing coating. The formulation may be hypotonic for the epithelium to which it is being delivered. Non-limiting examples of hypotonic formulations may be found in International Patent Publication No. WO2013/110028, the contents of which are herein incorporated by reference in their entirety.


In some embodiments, in order to enhance the delivery through the mucosal barrier the RNA (e.g., mRNA) vaccine formulation may comprise or be a hypotonic solution. Hypotonic solutions were found to increase the rate at which mucoinert particles such as, but not limited to, mucus-penetrating particles, were able to reach the vaginal epithelial surface (see e.g., Ensign et al. Biomaterials 2013 34(28):6922-9, the contents of which are herein incorporated by reference in their entirety).


In some embodiments, the RNA (e.g., mRNA) vaccine is formulated as a lipoplex, such as, without limitation, the ATUPLEX™ system, the DACC system, the DBTC system and other siRNA-lipoplex technology from Silence Therapeutics (London, United Kingdom), STEMFECT™ from STEMGENT® (Cambridge, MA), and polyethylenimine (PEI) or protamine-based targeted and non-targeted delivery of nucleic acids (Aleku et al. Cancer Res. 2008 68:9788-9798; Strumberg et al. Int J Clin Pharmacol Ther 2012 50:76-78; Santel et al., Gene Ther 2006 13:1222-1234; Santel et al., Gene Ther 2006 13:1360-1370; Gutbier et al., Pulm Pharmacol. Ther. 2010 23:334-344; Kaufmann et al. Microvasc Res 2010 80:286-293Weide et al. J Immunother. 2009 32:498-507; Weide et al. J Immunother. 2008 31:180-188; Pascolo Expert Opin. Biol. Ther. 4:1285-1294; Fotin-Mleczek et al., 2011 J. Immunother. 34:1-15; Song et al., Nature Biotechnol. 2005, 23:709-717; Peer et al., Proc Natl Acad Sci USA. 2007 6; 104:4095-4100; deFougerolles Hum Gene Ther. 2008 19:125-132, the contents of each of which are incorporated herein by reference in their entirety).


In some embodiments, such formulations may also be constructed or compositions altered such that they passively or actively are directed to different cell types in vivo, including but not limited to hepatocytes, immune cells, tumor cells, endothelial cells, antigen presenting cells, and leukocytes (Akinc et al. Mol Ther. 2010 18:1357-1364; Song et al., Nat Biotechnol. 2005 23:709-717; Judge et al., J Clin Invest. 2009 119:661-673; Kaufmann et al., Microvasc Res 2010 80:286-293; Santel et al., Gene Ther 2006 13:1222-1234; Santel et al., Gene Ther 2006 13:1360-1370; Gutbier et al., Pulm Pharmacol. Ther. 2010 23:334-344; Basha et al., Mol. Ther. 2011 19:2186-2200; Fenske and Cullis, Expert Opin Drug Deliv. 2008 5:25-44; Peer et al., Science. 2008 319:627-630; Peer and Lieberman, Gene Ther. 2011 18:1127-1133, the contents of each of which are incorporated herein by reference in their entirety). One example of passive targeting of formulations to liver cells includes the DLin-DMA, DLin-KC2-DMA and DLin-MC3-DMA-based lipid nanoparticle formulations, which have been shown to bind to apolipoprotein E and promote binding and uptake of these formulations into hepatocytes in vivo (Akinc et al. Mol Ther. 2010 18:1357-1364, the contents of which are incorporated herein by reference in their entirety). Formulations can also be selectively targeted through expression of different ligands on their surface as exemplified by, but not limited by, folate, transferrin, N-acetylgalactosamine (GalNAc), and antibody targeted approaches (Kolhatkar et al., Curr Drug Discov Technol. 2011 8:197-206; Musacchio and Torchilin, Front Biosci. 2011 16:1388-1412; Yu et al., Mol Membr Biol. 2010 27:286-298; Patil et al., Crit Rev Ther Drug Carrier Syst. 2008 25:1-61; Benoit et al., Biomacromolecules. 2011 12:2708-2714; Zhao et al., Expert Opin Drug Deliv. 2008 5:309-319; Akinc et al., Mol Ther. 2010 18:1357-1364; Srinivasan et al., Methods Mol Biol. 2012 820:105-116; Ben-Arie et al., Methods Mol Biol. 2012 757:497-507; Peer 2010 J Control Release. 20:63-68; Peer et al., Proc Natl Acad Sci USA. 2007 104:4095-4100; Kim et al., Methods Mol Biol. 2011 721:339-353; Subramanya et al., Mol Ther. 2010 18:2028-2037; Song et al., Nat Biotechnol. 2005 23:709-717; Peer et al., Science. 2008 319:627-630; Peer and Lieberman, Gene Ther. 2011 18:1127-1133, the contents of each of which are incorporated herein by reference in their entirety).


In some embodiments, the RNA (e.g., mRNA) vaccine is formulated as a solid lipid nanoparticle. A solid lipid nanoparticle (SLN) may be spherical with an average diameter between 10 to 1000 nm. SLN possess a solid lipid core matrix that can solubilize lipophilic molecules and may be stabilized with surfactants and/or emulsifiers. In some embodiments, the lipid nanoparticle may be a self-assembly lipid-polymer nanoparticle (see Zhang et al., ACS Nano, 2008, 2, pp 1696-1702; the contents of which are herein incorporated by reference in their entirety). As a non-limiting example, the SLN may be the SLN described in International Patent Publication No. WO2013/105101, the contents of which are herein incorporated by reference in their entirety. As another non-limiting example, the SLN may be made by the methods or processes described in International Patent Publication No. WO2013/105101, the contents of which are herein incorporated by reference in their entirety.


Liposomes, lipoplexes, or lipid nanoparticles may be used to improve the efficacy of polynucleotides directed protein production as these formulations may be able to increase cell transfection by the RNA (e.g., mRNA) vaccine; and/or increase the translation of encoded protein. One such example involves the use of lipid encapsulation to enable the effective systemic delivery of polyplex plasmid DNA (Heyes et al., Mol Ther. 2007 15:713-720; the contents of which are incorporated herein by reference in their entirety). The liposomes, lipoplexes, or lipid nanoparticles may also be used to increase the stability of the polynucleotide.


In some embodiments, the RNA (e.g., mRNA) vaccines of the present disclosure can be formulated for controlled release and/or targeted delivery. As used herein, “controlled release” refers to a pharmaceutical composition or compound release profile that conforms to a particular pattern of release to effect a therapeutic outcome. In some embodiments, the RNA (e.g., mRNA) vaccines may be encapsulated into a delivery agent described herein and/or known in the art for controlled release and/or targeted delivery. As used herein, the term “encapsulate” means to enclose, surround or encase. As it relates to the formulation of the compounds of the disclosure, encapsulation may be substantial, complete or partial. The term “substantially encapsulated” means that at least greater than 50, 60, 70, 80, 85, 90, 95, 96, 97, 98, 99, 99.9, 99.9 or greater than 99.999% of the pharmaceutical composition or compound of the disclosure may be enclosed, surrounded or encased within the delivery agent. “Partially encapsulation” means that less than 10, 10, 20, 30, 40 50 or less of the pharmaceutical composition or compound of the disclosure may be enclosed, surrounded or encased within the delivery agent. Advantageously, encapsulation may be determined by measuring the escape or the activity of the pharmaceutical composition or compound of the disclosure using fluorescence and/or electron micrograph. For example, at least 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 95, 96, 97, 98, 99, 99.9, 99.99 or greater than 99.99% of the pharmaceutical composition or compound of the disclosure are encapsulated in the delivery agent.


In some embodiments, the controlled release formulation may include, but is not limited to, tri-block co-polymers. As a non-limiting example, the formulation may include two different types of tri-block co-polymers (International Pub. No. WO2012/131104 and WO2012/131106, the contents of each of which are incorporated herein by reference in their entirety).


In some embodiments, the RNA (e.g., mRNA) vaccines may be encapsulated into a lipid nanoparticle or a rapidly eliminated lipid nanoparticle and the lipid nanoparticles or a rapidly eliminated lipid nanoparticle may then be encapsulated into a polymer, hydrogel and/or surgical sealant described herein and/or known in the art. As a non-limiting example, the polymer, hydrogel or surgical sealant may be PLGA, ethylene vinyl acetate (EVAc), poloxamer, GELSITE® (Nanotherapeutics, Inc. Alachua, FL), HYLENEX® (Halozyme Therapeutics, San Diego CA), surgical sealants such as fibrinogen polymers (Ethicon Inc. Cornelia, GA), TISSELL® (Baxter International, Inc. Deerfield, IL), PEG-based sealants, and COSEAL® (Baxter International, Inc Deerfield, IL).


In some embodiments, the lipid nanoparticle may be encapsulated into any polymer known in the art which may form a gel when injected into a subject. As another non-limiting example, the lipid nanoparticle may be encapsulated into a polymer matrix which may be biodegradable.


In some embodiments, the RNA (e.g., mRNA) vaccine formulation for controlled release and/or targeted delivery may also include at least one controlled release coating. Controlled release coatings include, but are not limited to, OPADRY®, polyvinylpyrrolidone/vinyl acetate copolymer, polyvinylpyrrolidone, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, EUDRAGIT RL®, EUDRAGIT RS® and cellulose derivatives such as ethylcellulose aqueous dispersions (AQUACOAT® and SURELEASE®).


In some embodiments, the RNA (e.g., mRNA) vaccine controlled release and/or targeted delivery formulation may comprise at least one degradable polyester which may contain polycationic side chains. Degradeable polyesters include, but are not limited to, poly(serine ester), poly(L-lactide-co-L-lysine), poly(4-hydroxy-L-proline ester), and combinations thereof. In some embodiments, the degradable polyesters may include a PEG conjugation to form a PEGylated polymer.


In some embodiments, the RNA (e.g., mRNA) vaccine controlled release and/or targeted delivery formulation comprising at least one polynucleotide may comprise at least one PEG and/or PEG related polymer derivatives as described in U.S. Pat. No. 8,404,222, the contents of which are incorporated herein by reference in their entirety.


In some embodiments, the RNA (e.g., mRNA) vaccine controlled release delivery formulation comprising at least one polynucleotide may be the controlled release polymer system described in US2013/0130348, the contents of which are incorporated herein by reference in their entirety.


In some embodiments, the RNA (e.g., mRNA) vaccines of the present disclosure may be encapsulated in a therapeutic nanoparticle, referred to herein as “therapeutic nanoparticle RNA (e.g., mRNA) vaccines.” Therapeutic nanoparticles may be formulated by methods described herein and known in the art such as, but not limited to, International Pub Nos. WO2010/005740, WO2010/030763, WO2010/005721, WO2010/005723, WO2012/054923, U.S. Publication Nos. US2011/0262491, US2010/0104645, US2010/0087337, US2010/0068285, US2011/0274759, US2010/0068286, US2012/0288541, US2013/0123351 and US2013/0230567 and U.S. Pat. Nos. 8,206,747, 8,293,276, 8,318,208 and 8,318,211; the contents of each of which are herein incorporated by reference in their entirety. In some embodiments, therapeutic polymer nanoparticles may be identified by the methods described in US Pub No. US2012/0140790, the contents of which are herein incorporated by reference in their entirety.


In some embodiments, the therapeutic nanoparticle RNA (e.g., mRNA) vaccine may be formulated for sustained release. As used herein, “sustained release” refers to a pharmaceutical composition or compound that conforms to a release rate over a specific period of time. The period of time may include, but is not limited to, hours, days, weeks, months and years. As a non-limiting example, the sustained release nanoparticle may comprise a polymer and a therapeutic agent such as, but not limited to, the polynucleotides of the present disclosure (see International Pub No. WO2010/075072 and US Pub No. US2010/0216804, US2011/0217377 and US2012/0201859, the contents of each of which are incorporated herein by reference in their entirety). In another non-limiting example, the sustained release formulation may comprise agents which permit persistent bioavailability such as, but not limited to, crystals, macromolecular gels and/or particulate suspensions (see U.S. Patent Publication No US2013/0150295, the contents of each of which are incorporated herein by reference in their entirety).


In some embodiments, the therapeutic nanoparticle RNA (e.g., mRNA) vaccines may be formulated to be target specific. As a non-limiting example, the therapeutic nanoparticles may include a corticosteroid (see International Pub. No. WO2011/084518, the contents of which are incorporated herein by reference in their entirety). As a non-limiting example, the therapeutic nanoparticles may be formulated in nanoparticles described in International Pub No. WO2008/121949, WO2010/005726, WO2010/005725, WO2011/084521 and US Pub No. US2010/0069426, US2012/0004293 and US2010/0104655, the contents of each of which are incorporated herein by reference in their entirety.


In some embodiments, the nanoparticles of the present disclosure may comprise a polymeric matrix. As a non-limiting example, the nanoparticle may comprise two or more polymers such as, but not limited to, polyethylenes, polycarbonates, polyanhydrides, polyhydroxyacids, polypropylfumerates, polycaprolactones, polyamides, polyacetals, polyethers, polyesters, poly(orthoesters), polycyanoacrylates, polyvinyl alcohols, polyurethanes, polyphosphazenes, polyacrylates, polymethacrylates, polycyanoacrylates, polyureas, polystyrenes, polyamines, polylysine, poly(ethylene imine), poly(serine ester), poly(L-lactide-co-L-lysine), poly(4-hydroxy-L-proline ester) or combinations thereof.


In some embodiments, the therapeutic nanoparticle comprises a diblock copolymer. In some embodiments, the diblock copolymer may include PEG in combination with a polymer such as, but not limited to, polyethylenes, polycarbonates, polyanhydrides, polyhydroxyacids, polypropylfumerates, polycaprolactones, polyamides, polyacetals, polyethers, polyesters, poly(orthoesters), polycyanoacrylates, polyvinyl alcohols, polyurethanes, polyphosphazenes, polyacrylates, polymethacrylates, polycyanoacrylates, polyureas, polystyrenes, polyamines, polylysine, poly(ethylene imine), poly(serine ester), poly(L-lactide-co-L-lysine), poly(4-hydroxy-L-proline ester) or combinations thereof. In yet another embodiment, the diblock copolymer may be a high-X diblock copolymer such as those described in International Patent Publication No. WO2013/120052, the contents of which are incorporated herein by reference in their entirety.


As a non-limiting example the therapeutic nanoparticle comprises a PLGA-PEG block copolymer (see U.S. Publication No. US2012/0004293 and U.S. Pat. No. 8,236,330, each of which is herein incorporated by reference in their entirety). In another non-limiting example, the therapeutic nanoparticle is a stealth nanoparticle comprising a diblock copolymer of PEG and PLA or PEG and PLGA (see U.S. Pat. No. 8,246,968 and International Publication No. WO2012/166923, the contents of each of which are herein incorporated by reference in their entirety). In yet another non-limiting example, the therapeutic nanoparticle is a stealth nanoparticle or a target-specific stealth nanoparticle as described in U.S. Patent Publication No. US2013/0172406, the contents of which are herein incorporated by reference in their entirety.


In some embodiments, the therapeutic nanoparticle may comprise a multiblock copolymer (see e.g., U.S. Pat. Nos. 8,263,665 and 8,287,910 and U.S. Patent Pub. No. US2013/0195987, the contents of each of which are herein incorporated by reference in their entirety).


In yet another non-limiting example, the lipid nanoparticle comprises the block copolymer PEG-PLGA-PEG (see e.g., the thermosensitive hydrogel (PEG-PLGA-PEG) was used as a TGF-beta1 gene delivery vehicle in Lee et al. Thermosensitive Hydrogel as a TGF-β1 Gene Delivery Vehicle Enhances Diabetic Wound Healing. Pharmaceutical Research, 2003 20(12): 1995-2000; as a controlled gene delivery system in Li et al. Controlled Gene Delivery System Based on Thermosensitive Biodegradable Hydrogel. Pharmaceutical Research 2003 20:884-888; and Chang et al., Non-ionic amphiphilic biodegradable PEG-PLGA-PEG copolymer enhances gene delivery efficiency in rat skeletal muscle. J Controlled Release. 2007 118:245-253, the contents of each of which are herein incorporated by reference in their entirety). The RNA (e.g., mRNA) vaccines of the present disclosure may be formulated in lipid nanoparticles comprising the PEG-PLGA-PEG block copolymer.


In some embodiments, the therapeutic nanoparticle may comprise a multiblock copolymer (see e.g., U.S. Pat. Nos. 8,263,665 and 8,287,910 and U.S. Patent Pub. No. US2013/0195987, the contents of each of which are herein incorporated by reference in their entirety).


In some embodiments, the block copolymers described herein may be included in a polyion complex comprising a non-polymeric micelle and the block copolymer. (see e.g., U.S. Publication No. 2012/0076836, the contents of which are herein incorporated by reference in their entirety).


In some embodiments, the therapeutic nanoparticle may comprise at least one acrylic polymer. Acrylic polymers include but are not limited to, acrylic acid, methacrylic acid, acrylic acid and methacrylic acid copolymers, methyl methacrylate copolymers, ethoxyethyl methacrylates, cyanoethyl methacrylate, amino alkyl methacrylate copolymer, poly(acrylic acid), poly(methacrylic acid), polycyanoacrylates and combinations thereof.


In some embodiments, the therapeutic nanoparticles may comprise at least one poly(vinyl ester) polymer. The poly(vinyl ester) polymer may be a copolymer such as a random copolymer. As a non-limiting example, the random copolymer may have a structure such as those described in International Application No. WO2013/032829 or U.S. Patent Publication No US2013/0121954, the contents of each of which are herein incorporated by reference in their entirety. In some embodiments, the poly(vinyl ester) polymers may be conjugated to the polynucleotides described herein.


In some embodiments, the therapeutic nanoparticle may comprise at least one diblock copolymer. The diblock copolymer may be, but it not limited to, a poly(lactic) acid-poly(ethylene)glycol copolymer (see, e.g., International Patent Publication No. WO2013/044219, the contents of which are herein incorporated by reference in their entirety). As a non-limiting example, the therapeutic nanoparticle may be used to treat cancer (see International publication No. WO2013/044219, the contents of which are herein incorporated by reference in their entirety).


In some embodiments, the therapeutic nanoparticles may comprise at least one cationic polymer described herein and/or known in the art.


In some embodiments, the therapeutic nanoparticles may comprise at least one amine-containing polymer such as, but not limited to polylysine, polyethylene imine, poly(amidoamine) dendrimers, poly(beta-amino esters) (see, e.g., U.S. Pat. No. 8,287,849, the contents of which are herein incorporated by reference in their entirety) and combinations thereof.


In some embodiments, the nanoparticles described herein may comprise an amine cationic lipid such as those described in International Patent Application No. WO2013/059496, the contents of which are herein incorporated by reference in their entirety. In some embodiments, the cationic lipids may have an amino-amine or an amino-amide moiety.


In some embodiments, the therapeutic nanoparticles may comprise at least one degradable polyester which may contain polycationic side chains. Degradeable polyesters include, but are not limited to, poly(serine ester), poly(L-lactide-co-L-lysine), poly(4-hydroxy-L-proline ester), and combinations thereof. In some embodiments, the degradable polyesters may include a PEG conjugation to form a PEGylated polymer.


In some embodiments, the synthetic nanocarriers may contain an immunostimulatory agent to enhance the immune response from delivery of the synthetic nanocarrier. As a non-limiting example, the synthetic nanocarrier may comprise a Th1 immunostimulatory agent, which may enhance a Th1-based response of the immune system (see International Pub No. WO2010/123569 and U.S. Publication No. US2011/0223201, the contents of each of which are herein incorporated by reference in their entirety).


In some embodiments, the synthetic nanocarriers may be formulated for targeted release. In some embodiments, the synthetic nanocarrier is formulated to release the polynucleotides at a specified pH and/or after a desired time interval. As a non-limiting example, the synthetic nanoparticle may be formulated to release the RNA (e.g., mRNA) vaccines after 24 hours and/or at a pH of 4.5 (see International Publication Nos. WO2010/138193 and WO2010/138194 and US Pub Nos. US2011/0020388 and US2011/0027217, each of which is herein incorporated by reference in their entireties).


In some embodiments, the synthetic nanocarriers may be formulated for controlled and/or sustained release of the polynucleotides described herein. As a non-limiting example, the synthetic nanocarriers for sustained release may be formulated by methods known in the art, described herein and/or as described in International Pub No. WO2010/138192 and US Pub No. 2010/0303850, each of which is herein incorporated by reference in their entirety.


In some embodiments, the RNA (e.g., mRNA) vaccine may be formulated for controlled and/or sustained release wherein the formulation comprises at least one polymer that is a crystalline side chain (CYSC) polymer. CYSC polymers are described in U.S. Pat. No. 8,399,007, herein incorporated by reference in its entirety.


In some embodiments, the synthetic nanocarrier may be formulated for use as a vaccine. In some embodiments, the synthetic nanocarrier may encapsulate at least one polynucleotide which encode at least one antigen. As a non-limiting example, the synthetic nanocarrier may include at least one antigen and an excipient for a vaccine dosage form (see International Publication No. WO2011/150264 and U.S. Publication No. US2011/0293723, the contents of each of which are herein incorporated by reference in their entirety). As another non-limiting example, a vaccine dosage form may include at least two synthetic nanocarriers with the same or different antigens and an excipient (see International Publication No. WO2011/150249 and U.S. Publication No. US2011/0293701, the contents of each of which are herein incorporated by reference in their entirety). The vaccine dosage form may be selected by methods described herein, known in the art and/or described in International Publication No. WO2011/150258 and U.S. Publication No. US2012/0027806, the contents of each of which are herein incorporated by reference in their entirety).


In some embodiments, the synthetic nanocarrier may comprise at least one polynucleotide which encodes at least one adjuvant. As non-limiting example, the adjuvant may comprise dimethyldioctadecylammonium-bromide, dimethyldioctadecylammonium-chloride, dimethyldioctadecylammonium-phosphate or dimethyldioctadecylammonium-acetate (DDA) and an apolar fraction or part of said apolar fraction of a total lipid extract of a mycobacterium (see, e.g., U.S. Pat. No. 8,241,610, the content of which is herein incorporated by reference in its entirety). In some embodiments, the synthetic nanocarrier may comprise at least one polynucleotide and an adjuvant. As a non-limiting example, the synthetic nanocarrier comprising and adjuvant may be formulated by the methods described in International Publication No. WO2011/150240 and U.S. Publication No. US2011/0293700, the contents of each of which are herein incorporated by reference in their entirety.


In some embodiments, the synthetic nanocarrier may encapsulate at least one polynucleotide that encodes a peptide, fragment or region from a virus. As a non-limiting example, the synthetic nanocarrier may include, but is not limited to, any of the nanocarriers described in International Publication No. WO2012/024621, WO2012/02629, WO2012/024632 and U.S. Publication No. US2012/0064110, US2012/0058153 and US2012/0058154, the contents of each of which are herein incorporated by reference in their entirety.


In some embodiments, the synthetic nanocarrier may be coupled to a polynucleotide which may be able to trigger a humoral and/or cytotoxic T lymphocyte (CTL) response (see, e.g., International Publication No. WO2013/019669, the contents of which are herein incorporated by reference in their entirety).


In some embodiments, the RNA (e.g., mRNA) vaccine may be encapsulated in, linked to and/or associated with zwitterionic lipids. Non-limiting examples of zwitterionic lipids and methods of using zwitterionic lipids are described in U.S. Patent Publication No. US2013/0216607, the contents of which are herein incorporated by reference in their entirety.


In some aspects, the zwitterionic lipids may be used in the liposomes and lipid nanoparticles described herein.


In some embodiments, the RNA (e.g., mRNA) vaccine may be formulated in colloid nanocarriers as described in U.S. Patent Publication No. US2013/0197100, the contents of which are herein incorporated by reference in their entirety.


In some embodiments, the nanoparticle may be optimized for oral administration. The nanoparticle may comprise at least one cationic biopolymer such as, but not limited to, chitosan or a derivative thereof. As a non-limiting example, the nanoparticle may be formulated by the methods described in U.S. Publication No. US2012/0282343, the contents of which are herein incorporated by reference in their entirety.


In some embodiments, LNPs comprise the lipid KL52 (an amino-lipid disclosed in U.S. Application Publication No. 2012/0295832, the contents of which are herein incorporated by reference in their entirety. Activity and/or safety (as measured by examining one or more of ALT/AST, white blood cell count and cytokine induction, for example) of LNP administration may be improved by incorporation of such lipids. LNPs comprising KL52 may be administered intravenously and/or in one or more doses. In some embodiments, administration of LNPs comprising KL52 results in equal or improved mRNA and/or protein expression as compared to LNPs comprising MC3.


In some embodiments, RNA (e.g., mRNA) vaccine may be delivered using smaller LNPs. Such particles may comprise a diameter from below 0.1 um up to 100 nm such as, but not limited to, less than 0.1 um, less than 1.0 um, less than 5 um, less than 10 um, less than 15 um, less than 20 um, less than 25 um, less than 30 um, less than 35 um, less than 40 um, less than 50 um, less than 55 um, less than 60 um, less than 65 um, less than 70 um, less than 75 um, less than 80 um, less than 85 um, less than 90 um, less than 95 um, less than 100 um, less than 125 um, less than 150 um, less than 175 um, less than 200 um, less than 225 um, less than 250 um, less than 275 um, less than 300 um, less than 325 um, less than 350 um, less than 375 um, less than 400 um, less than 425 um, less than 450 um, less than 475 um, less than 500 um, less than 525 um, less than 550 um, less than 575 um, less than 600 um, less than 625 um, less than 650 um, less than 675 um, less than 700 um, less than 725 um, less than 750 um, less than 775 um, less than 800 um, less than 825 um, less than 850 um, less than 875 um, less than 900 um, less than 925 um, less than 950 um, less than 975 um, or less than 1000 um.


In some embodiments, RNA (e.g., mRNA) vaccines may be delivered using smaller LNPs, which may comprise a diameter from about 1 nm to about 100 nm, from about 1 nm to about 10 nm, about 1 nm to about 20 nm, from about 1 nm to about 30 nm, from about 1 nm to about 40 nm, from about 1 nm to about 50 nm, from about 1 nm to about 60 nm, from about 1 nm to about 70 nm, from about 1 nm to about 80 nm, from about 1 nm to about 90 nm, from about 5 nm to about from 100 nm, from about 5 nm to about 10 nm, about 5 nm to about 20 nm, from about 5 nm to about 30 nm, from about 5 nm to about 40 nm, from about 5 nm to about 50 nm, from about 5 nm to about 60 nm, from about 5 nm to about 70 nm, from about 5 nm to about 80 nm, from about 5 nm to about 90 nm, about 10 to about 50 nm, from about 20 to about 50 nm, from about 30 to about 50 nm, from about 40 to about 50 nm, from about 20 to about 60 nm, from about 30 to about 60 nm, from about 40 to about 60 nm, from about 20 to about 70 nm, from about 30 to about 70 nm, from about 40 to about 70 nm, from about 50 to about 70 nm, from about 60 to about 70 nm, from about 20 to about 80 nm, from about 30 to about 80 nm, from about 40 to about 80 nm, from about 50 to about 80 nm, from about 60 to about 80 nm, from about 20 to about 90 nm, from about 30 to about 90 nm, from about 40 to about 90 nm, from about 50 to about 90 nm, from about 60 to about 90 nm and/or from about 70 to about 90 nm.


In some embodiments, such LNPs are synthesized using methods comprising microfluidic mixers. Examples of microfluidic mixers may include, but are not limited to, a slit interdigital micromixer including, but not limited to those manufactured by Microinnova (Allerheiligen bei Wildon, Austria) and/or a staggered herringbone micromixer (SHM) (Zhigaltsev, I. V. et al., Bottom-up design and synthesis of limit size lipid nanoparticle systems with aqueous and triglyceride cores using millisecond microfluidic mixing have been published (Langmuir. 2012. 28:3633-40; Belliveau, N. M. et al., Microfluidic synthesis of highly potent limit-size lipid nanoparticles for in vivo delivery of siRNA. Molecular Therapy-Nucleic Acids. 2012. 1:e37; Chen, D. et al., Rapid discovery of potent siRNA-containing lipid nanoparticles enabled by controlled microfluidic formulation. J Am Chem Soc. 2012. 134(16):6948-51, the contents of each of which are herein incorporated by reference in their entirety). In some embodiments, methods of LNP generation comprising SHM, further comprise the mixing of at least two input streams wherein mixing occurs by microstructure-induced chaotic advection (MICA). According to this method, fluid streams flow through channels present in a herringbone pattern causing rotational flow and folding the fluids around each other. This method may also comprise a surface for fluid mixing wherein the surface changes orientations during fluid cycling. Methods of generating LNPs using SHM include those disclosed in U.S. Application Publication Nos. 2004/0262223 and 2012/0276209, the contents of each of which are herein incorporated by reference in their entirety.


In some embodiments, the RNA (e.g., mRNA) vaccine of the present disclosure may be formulated in lipid nanoparticles created using a micromixer such as, but not limited to, a Slit Interdigital Microstructured Mixer (SIMM-V2) or a Standard Slit Interdigital Micro Mixer (SSIMM) or Caterpillar (CPMM) or Impinging-jet (IJMM)from the Institut fUr Mikrotechnik Mainz GmbH, Mainz Germany).


In some embodiments, the RNA (e.g., mRNA) vaccines of the present disclosure may be formulated in lipid nanoparticles created using microfluidic technology (see, e.g., Whitesides, George M. The Origins and the Future of Microfluidics. Nature, 2006 442: 368-373; and Abraham et al. Chaotic Mixer for Microchannels. Science, 2002 295: 647-651; each of which is herein incorporated by reference in its entirety). As a non-limiting example, controlled microfluidic formulation includes a passive method for mixing streams of steady pressure-driven flows in micro channels at a low Reynolds number (see, e.g., Abraham et al. Chaotic Mixer for Microchannels. Science, 2002 295: 647-651, the contents of which are herein incorporated by reference in their entirety).


In some embodiments, the RNA (e.g., mRNA) vaccines of the present disclosure may be formulated in lipid nanoparticles created using a micromixer chip such as, but not limited to, those from Harvard Apparatus (Holliston, MA) or Dolomite Microfluidics (Royston, UK). A micromixer chip can be used for rapid mixing of two or more fluid streams with a split and recombine mechanism.


In some embodiments, the RNA (e.g., mRNA) vaccines of the disclosure may be formulated for delivery using the drug encapsulating microspheres described in International Patent Publication No. WO2013063468 or U.S. Pat. No. 8,440,614, the contents of each of which are herein incorporated by reference in their entirety. The microspheres may comprise a compound of the formula (I), (II), (III), (IV), (V) or (VI) as described in International Patent Publication No. WO2013/063468, the contents of which are herein incorporated by reference in their entirety. In some embodiments, the amino acid, peptide, polypeptide, lipids (APPL) are useful in delivering the RNA (e.g., mRNA) vaccines of the disclosure to cells (see International Patent Publication No. WO2013/063468, the contents of which are herein incorporated by reference in their entirety).


In some embodiments, the RNA (e.g., mRNA) vaccines of the disclosure may be formulated in lipid nanoparticles having a diameter from about 10 to about 100 nm such as, but not limited to, about 10 to about 20 nm, about 10 to about 30 nm, about 10 to about 40 nm, about 10 to about 50 nm, about 10 to about 60 nm, about 10 to about 70 nm, about 10 to about 80 nm, about 10 to about 90 nm, about 20 to about 30 nm, about 20 to about 40 nm, about 20 to about 50 nm, about 20 to about 60 nm, about 20 to about 70 nm, about 20 to about 80 nm, about 20 to about 90 nm, about 20 to about 100 nm, about 30 to about 40 nm, about 30 to about 50 nm, about 30 to about 60 nm, about 30 to about 70 nm, about 30 to about 80 nm, about 30 to about 90 nm, about 30 to about 100 nm, about 40 to about 50 nm, about 40 to about 60 nm, about 40 to about 70 nm, about 40 to about 80 nm, about 40 to about 90 nm, about 40 to about 100 nm, about 50 to about 60 nm, about 50 to about 70 nm about 50 to about 80 nm, about 50 to about 90 nm, about 50 to about 100 nm, about 60 to about 70 nm, about 60 to about 80 nm, about 60 to about 90 nm, about 60 to about 100 nm, about 70 to about 80 nm, about 70 to about 90 nm, about 70 to about 100 nm, about 80 to about 90 nm, about 80 to about 100 nm and/or about 90 to about 100 nm.


In some embodiments, the lipid nanoparticles may have a diameter from about 10 to 500 nm.


In some embodiments, the lipid nanoparticle may have a diameter greater than 100 nm, greater than 150 nm, greater than 200 nm, greater than 250 nm, greater than 300 nm, greater than 350 nm, greater than 400 nm, greater than 450 nm, greater than 500 nm, greater than 550 nm, greater than 600 nm, greater than 650 nm, greater than 700 nm, greater than 750 nm, greater than 800 nm, greater than 850 nm, greater than 900 nm, greater than 950 nm or greater than 1000 nm.


In some embodiments, the lipid nanoparticle may be a limit size lipid nanoparticle described in International Patent Publication No. WO2013/059922, the contents of which are herein incorporated by reference in their entirety. The limit size lipid nanoparticle may comprise a lipid bilayer surrounding an aqueous core or a hydrophobic core; where the lipid bilayer may comprise a phospholipid such as, but not limited to, diacylphosphatidylcholine, a diacylphosphatidylethanolamine, a ceramide, a sphingomyelin, a dihydrosphingomyelin, a cephalin, a cerebroside, a C8-C20 fatty acid diacylphophatidylcholine, and 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC). In some embodiments, the limit size lipid nanoparticle may comprise a polyethylene glycol-lipid such as, but not limited to, DLPE-PEG, DMPE-PEG, DPPC-PEG and DSPE-PEG.


In some embodiments, the RNA (e.g., mRNA) vaccines may be delivered, localized and/or concentrated in a specific location using the delivery methods described in International Patent Publication No. WO2013/063530, the contents of which are herein incorporated by reference in their entirety. As a non-limiting example, a subject may be administered an empty polymeric particle prior to, simultaneously with or after delivering the RNA (e.g., mRNA) vaccines to the subject. The empty polymeric particle undergoes a change in volume once in contact with the subject and becomes lodged, embedded, immobilized or entrapped at a specific location in the subject.


In some embodiments, the RNA (e.g., mRNA) vaccines may be formulated in an active substance release system (see, e.g., U.S. Patent Publication No. US2013/0102545, the contents of which are herein incorporated by reference in their entirety). The active substance release system may comprise 1) at least one nanoparticle bonded to an oligonucleotide inhibitor strand which is hybridized with a catalytically active nucleic acid and 2) a compound bonded to at least one substrate molecule bonded to a therapeutically active substance (e.g., polynucleotides described herein), where the therapeutically active substance is released by the cleavage of the substrate molecule by the catalytically active nucleic acid.


In some embodiments, the RNA (e.g., mRNA) vaccines may be formulated in a nanoparticle comprising an inner core comprising a non-cellular material and an outer surface comprising a cellular membrane. The cellular membrane may be derived from a cell or a membrane derived from a virus. As a non-limiting example, the nanoparticle may be made by the methods described in International Patent Publication No. WO2013/052167, the contents of which are herein incorporated by reference in their entirety. As another non-limiting example, the nanoparticle described in International Patent Publication No. WO2013/052167, the contents of which are herein incorporated by reference in their entirety, may be used to deliver the RNA (e.g., mRNA) vaccines described herein.


In some embodiments, the RNA (e.g., mRNA) vaccines may be formulated in porous nanoparticle-supported lipid bilayers (protocells). Protocells are described in International Patent Publication No. WO2013/056132, the contents of which are herein incorporated by reference in their entirety.


In some embodiments, the RNA (e.g., mRNA) vaccines described herein may be formulated in polymeric nanoparticles as described in or made by the methods described in U.S. Pat. Nos. 8,420,123 and 8,518,963 and European Patent No. EP2073848B1, the contents of each of which are herein incorporated by reference in their entirety. As a non-limiting example, the polymeric nanoparticle may have a high glass transition temperature such as the nanoparticles described in or nanoparticles made by the methods described in U.S. Pat. No. 8,518,963, the contents of which are herein incorporated by reference in their entirety. As another non-limiting example, the polymer nanoparticle for oral and parenteral formulations may be made by the methods described in European Patent No. EP2073848B1, the contents of which are herein incorporated by reference in their entirety.


In some embodiments, the RNA (e.g., mRNA) vaccines described herein may be formulated in nanoparticles used in imaging. The nanoparticles may be liposome nanoparticles such as those described in U.S. Patent Publication No US2013/0129636, herein incorporated by reference in its entirety. As a non-limiting example, the liposome may comprise gadolinium(III)2-{4,7-bis-carboxymethyl-10-[(N,N-distearylamidomethyl-N′-amido-methyl]-1,4,7,10-tetra-azacyclododec-1-yl}-acetic acid and a neutral, fully saturated phospholipid component (see, e.g., U.S. Patent Publication No US2013/0129636, the contents of which are herein incorporated by reference in their entirety).


In some embodiments, the nanoparticles which may be used in the present disclosure are formed by the methods described in U.S. Patent Application No. US2013/0130348, the contents of which are herein incorporated by reference in their entirety.


The nanoparticles of the present disclosure may further include nutrients such as, but not limited to, those which deficiencies can lead to health hazards from anemia to neural tube defects (see, e.g., the nanoparticles described in International Patent Publication No WO2013/072929, the contents of which are herein incorporated by reference in their entirety). As a non-limiting example, the nutrient may be iron in the form of ferrous, ferric salts or elemental iron, iodine, folic acid, vitamins or micronutrients.


In some embodiments, the RNA (e.g., mRNA) vaccines of the present disclosure may be formulated in a swellable nanoparticle. The swellable nanoparticle may be, but is not limited to, those described in U.S. Pat. No. 8,440,231, the contents of which are herein incorporated by reference in their entirety. As a non-limiting embodiment, the swellable nanoparticle may be used for delivery of the RNA (e.g., mRNA) vaccines of the present disclosure to the pulmonary system (see, e.g., U.S. Pat. No. 8,440,231, the contents of which are herein incorporated by reference in their entirety).


The RNA (e.g., mRNA) vaccines of the present disclosure may be formulated in polyanhydride nanoparticles such as, but not limited to, those described in U.S. Pat. No. 8,449,916, the contents of which are herein incorporated by reference in their entirety.


The nanoparticles and microparticles of the present disclosure may be geometrically engineered to modulate macrophage and/or the immune response. In some embodiments, the geometrically engineered particles may have varied shapes, sizes and/or surface charges in order to incorporated the polynucleotides of the present disclosure for targeted delivery such as, but not limited to, pulmonary delivery (see, e.g., International Publication No WO2013/082111, the contents of which are herein incorporated by reference in their entirety). Other physical features the geometrically engineering particles may have include, but are not limited to, fenestrations, angled arms, asymmetry and surface roughness, charge which can alter the interactions with cells and tissues. As a non-limiting example, nanoparticles of the present disclosure may be made by the methods described in International Publication No WO2013/082111, the contents of which are herein incorporated by reference in their entirety.


In some embodiments, the nanoparticles of the present disclosure may be water soluble nanoparticles such as, but not limited to, those described in International Publication No. WO2013/090601, the contents of which are herein incorporated by reference in their entirety. The nanoparticles may be inorganic nanoparticles which have a compact and zwitterionic ligand in order to exhibit good water solubility. The nanoparticles may also have small hydrodynamic diameters (HD), stability with respect to time, pH, and salinity and a low level of non-specific protein binding.


In some embodiments the nanoparticles of the present disclosure may be developed by the methods described in U.S. Patent Publication No. US2013/0172406, the contents of which are herein incorporated by reference in their entirety.


In some embodiments, the nanoparticles of the present disclosure are stealth nanoparticles or target-specific stealth nanoparticles such as, but not limited to, those described in U.S. Patent Publication No. US2013/0172406, the contents of which are herein incorporated by reference in their entirety. The nanoparticles of the present disclosure may be made by the methods described in U.S. Patent Publication No. US2013/0172406, the contents of which are herein incorporated by reference in their entirety.


In some embodiments, the stealth or target-specific stealth nanoparticles may comprise a polymeric matrix. The polymeric matrix may comprise two or more polymers such as, but not limited to, polyethylenes, polycarbonates, polyanhydrides, polyhydroxyacids, polypropylfumerates, polycaprolactones, polyamides, polyacetals, polyethers, polyesters, poly(orthoesters), polycyanoacrylates, polyvinyl alcohols, polyurethanes, polyphosphazenes, polyacrylates, polymethacrylates, polycyanoacrylates, polyureas, polystyrenes, polyamines, polyesters, polyanhydrides, polyethers, polyurethanes, polymethacrylates, polyacrylates, polycyanoacrylates or combinations thereof.


In some embodiments, the nanoparticle may be a nanoparticle-nucleic acid hybrid structure having a high density nucleic acid layer. As a non-limiting example, the nanoparticle-nucleic acid hybrid structure may made by the methods described in U.S. Patent Publication No. US2013/0171646, the contents of which are herein incorporated by reference in their entirety. The nanoparticle may comprise a nucleic acid such as, but not limited to, polynucleotides described herein and/or known in the art.


At least one of the nanoparticles of the present disclosure may be embedded in in the core a nanostructure or coated with a low density porous 3-D structure or coating which is capable of carrying or associating with at least one payload within or on the surface of the nanostructure. Non-limiting examples of the nanostructures comprising at least one nanoparticle are described in International Patent Publication No. WO2013/123523, the contents of which are herein incorporated by reference in their entirety.


In some embodiments the RNA (e.g., mRNA) vaccine may be associated with a cationic or polycationic compounds, including protamine, nucleoline, spermine or spermidine, or other cationic peptides or proteins, such as poly-L-lysine (PLL), polyarginine, basic polypeptides, cell penetrating peptides (CPPs), including HIV-binding peptides, HIV-1 Tat (HIV), Tat-derived peptides, Penetratin, VP22 derived or analog peptides, Pestivirus Erns, HSV, VP22 (Herpes simplex), MAP, KALA or protein transduction domains (PTDs), PpT620, prolin-rich peptides, arginine-rich peptides, lysine-rich peptides, MPG-peptide(s), Pep-1, L-oligomers, Calcitonin peptide(s), Antennapedia-derived peptides (particularly from Drosophila antennapedia), pAntp, plsl, FGF, Lactoferrin, Transportan, Buforin-2, Bac715-24, SynB, SynB, pVEC, hCT-derived peptides, SAP, histones, cationic polysaccharides, for example chitosan, polybrene, cationic polymers, e.g. polyethyleneimine (PEI), cationic lipids, e.g. DOTMA: [1-(2,3-sioleyloxy)propyl)]-N,N,N-trimethylammonium chloride, DMRIE, di-C14-amidine, DOTIM, SAINT, DC-Chol, BGTC, CTAP, DOPC, DODAP, DOPE: Dioleyl phosphatidylethanol-amine, DOSPA, DODAB, DOIC, DMEPC, DOGS: Dioctadecylamidoglicylspermin, DIMRI: Dimyristooxypropyl dimethyl hydroxyethyl ammonium bromide, DOTAP: dioleoyloxy-3-(trimethylammonio)propane, DC-6-14: O,O -ditetradecanoyl-N-. alpha.-trimethylammonioacetyl)diethanolamine chloride, CLIP 1: rac-[(2,3-dioctadecyloxypropyl)(2-hydroxyethyl)]-dimethylammonium chloride, CLIP6: rac-[2(2,3-dihexadecyloxypropyloxymethyloxy)ethyl]-trimethylammonium, CLIP9: rac-[2(2,3-dihexadecyloxypropyloxysuccinyloxy)ethyl]-trimethylammo-nium, oligofectamine, or cationic or polycationic polymers, e.g. modified polyaminoacids, such as beta-aminoacid-polymers or reversed polyamides, etc., modified polyethylenes, such as PVP (poly(N-ethyl-4-vinylpyridinium bromide)), etc., modified acrylates, such as pDMAEMA (poly(dimethylaminoethyl methylacrylate)), etc., modified amidoamines such as pAMAM (poly(amidoamine)), etc., modified polybetaminoester (PBAE), such as diamine end modified 1,4 butanediol diacrylate-co-5-amino-1-pentanol polymers, etc., dendrimers, such as polypropylamine dendrimers or pAMAM based dendrimers, etc., polyimine(s), such as PEI: poly(ethyleneimine), poly(propyleneimine), etc., polyallylamine, sugar backbone based polymers, such as cyclodextrin based polymers, dextran based polymers, chitosan, etc., silan backbone based polymers, such as PMOXA-PDMS copolymers, etc., blockpolymers consisting of a combination of one or more cationic blocks (e.g. selected from a cationic polymer as mentioned above) and of one or more hydrophilic or hydrophobic blocks (e.g. polyethyleneglycole), etc.


In other embodiments the RNA (e.g., mRNA) vaccine is not associated with a cationic or polycationic compounds.


In some embodiments, a nanoparticle comprises compounds of Formula (I):




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    • or a salt or isomer thereof, wherein:

    • R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′R′;

    • R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;

    • R4 is selected from the group consisting of a C3-6 carbocycle, —(CH2)nQ, —(CH2)nCHQR, —CHQR,-CQ(R)2, and unsubstituted C1-6 alkyl, where Q is selected from a carbocycle, heterocycle, —OR, —O(CH2)nN(R)2, —C(O)OR, —OC(O)R, —CX3, —CX2H, —CXH2, —CN, —N(R)2, —C(O)N(R)2, —N(R)C(O)R, —N(R)S(O)2R, —N(R)C(O)N(R)2, —N(R)C(S)N(R)2, —N(R)R8, —O(CH2)nOR, —N(R)C(═NR9)N(R)2, —N(R)C(═CHR9)N(R)2, —OC(O)N(R)2, —N(R)C(O)OR, —N(OR)C(O)R, —N(OR)S(O)2R, —N(OR)C(O)OR, —N(OR)C(O)N(R)2, —N(OR)C(S)N(R)2, —N(OR)C(═NR9)N(R)2, —N(OR)C(═CHR9)N(R)2, —C(═NR9)N(R)2, —C(═NR9)R, —C(O)N(R)OR, and —C(R)N(R)2C(O)OR, and each n is independently selected from 1, 2, 3, 4, and 5;

    • each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′)C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O)(OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;

    • R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • R8 is selected from the group consisting of C3-6 carbocycle and heterocycle;

    • R9 is selected from the group consisting of H, CN, NO2, C1-6 alkyl, —OR, —S(O)2R, —S(O)2N(R)2, C2-6 alkenyl, C3-6 carbocycle and heterocycle; each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;

    • each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;

    • each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;

    • each Y is independently a C3-6 carbocycle;

    • each X is independently selected from the group consisting of F, Cl, Br, and I; and

    • m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.





In some embodiments, a subset of compounds of Formula (I) includes those in which when R4 is —(CH2)nQ, —(CH2)nCHQR, —CHQR, or —CQ(R)2, then (i) Q is not —N(R)2 when n is 1, 2, 3, 4 or 5, or (ii) Q is not 5, 6, or 7-membered heterocycloalkyl when n is 1 or 2.


In some embodiments, another subset of compounds of Formula (I) includes those in which

    • R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′R′;
    • R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;
    • R4 is selected from the group consisting of a C3-6 carbocycle, —(CH2)nQ, —(CH2)nCHQR, —CHQR,-CQ(R)2, and unsubstituted C1-6 alkyl, where Q is selected from a C3-6 carbocycle, a 5- to 14-membered heteroaryl having one or more heteroatoms selected from N, O, and S, —OR, —O(CH2)nN(R)2, —C(O)OR, —OC(O)R, —CX3, —CX2H, —CXH2, —CN, —C(O)N(R)2, —N(R)C(O)R, —N(R)S(O)2R, —N(R)C(O)N(R)2, —N(R)C(S)N(R)2, —CRN(R)2C(O)OR, —N(R)R8, —O(CH2)nOR, —N(R)C(═NR9)N(R)2, —N(R)C(═CHR9)N(R)2, —OC(O)N(R)2, —N(R)C(O)OR, —N(OR)C(O)R, —N(OR)S(O)2R, —N(OR)C(O)OR, —N(OR)C(O)N(R)2, —N(OR)C(S)N(R)2, —N(OR)C(═NR9)N(R)2, —N(OR)C(═CHR9)N(R)2, —C(═NR9)N(R)2, —C(═NR9)R, —C(O)N(R)OR, and a 5- to 14-membered heterocycloalkyl having one or more heteroatoms selected from N, O, and S which is substituted with one or more substituents selected from oxo (═O), OH, amino, mono- or di-alkylamino, and C1-3 alkyl, and each n is independently selected from 1, 2, 3, 4, and 5;
    • each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′)C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O)(OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;
    • R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • R8 is selected from the group consisting of C3-6 carbocycle and heterocycle;
    • R9 is selected from the group consisting of H, CN, NO2, C1-6 alkyl, —OR, —S(O)2R, —S(O)2N(R)2, C2-6 alkenyl, C3-6 carbocycle and heterocycle;
    • each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;
    • each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;
    • each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;
    • each Y is independently a C3-6 carbocycle;
    • each X is independently selected from the group consisting of F, Cl, Br, and I; and
    • m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
    • or salts or isomers thereof.


In some embodiments, another subset of compounds of Formula (I) includes those in which

    • R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′R′;
    • R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;
    • R4 is selected from the group consisting of a C3-6 carbocycle, —(CH2)nQ, —(CH2)nCHQR, —CHQR,-CQ(R)2, and unsubstituted C1-6 alkyl, where Q is selected from a C3-6 carbocycle, a 5- to 14-membered heterocycle having one or more heteroatoms selected from N, O, and S, —OR, —O(CH2)nN(R)2, —C(O)OR, —OC(O)R, —CX3, —CX2H, —CXH2, —CN, —C(O)N(R)2, —N(R)C(O)R, —N(R)S(O)2R, —N(R)C(O)N(R)2, —N(R)C(S)N(R)2, —CRN(R)2C(O)OR, —N(R)R8, —O(CH2)nOR, —N(R)C(═NR9)N(R)2, —N(R)C(═CHR9)N(R)2, —OC(O)N(R)2, —N(R)C(O)OR, —N(OR)C(O)R, —N(OR)S(O)2R, —N(OR)C(O)OR, —N(OR)C(O)N(R)2, —N(OR)C(S)N(R)2, —N(OR)C(═NR9)N(R)2, —N(OR)C(═CHR9)N(R)2, —C(═NR9)R, —C(O)N(R)OR, and —C(═NR9)N(R)2, and each n is independently selected from 1, 2, 3, 4, and 5; and when Q is a 5- to 14-membered heterocycle and (i) R4 is —(CH2)nQ in which n is 1 or 2, or (ii) R4 is —(CH2)nCHQR in which n is 1, or (iii) R4 is-CHQR, and -CQ(R)2, then Q is either a 5- to 14-membered heteroaryl or 8- to 14-membered heterocycloalkyl;
    • each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′)C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O)(OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;
    • R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • R8 is selected from the group consisting of C3-6 carbocycle and heterocycle;
    • R9 is selected from the group consisting of H, CN, NO2, C1-6 alkyl, —OR, —S(O)2R, —S(O)2N(R)2, C2-6 alkenyl, C3-6 carbocycle and heterocycle; each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;
    • each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;
    • each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;
    • each Y is independently a C3-6 carbocycle;
    • each X is independently selected from the group consisting of F, Cl, Br, and I; and
    • m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
    • or salts or isomers thereof.


In some embodiments, another subset of compounds of Formula (I) includes those in which

    • R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′R′;
    • R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;
    • R4 is selected from the group consisting of a C3-6 carbocycle, —(CH2)nQ, —(CH2)nCHQR, —CHQR,-CQ(R)2, and unsubstituted C1-6 alkyl, where Q is selected from a C3-6 carbocycle, a 5- to 14-membered heteroaryl having one or more heteroatoms selected from N, O, and S, —OR, —O(CH2)nN(R)2, —C(O)OR, —OC(O)R, —CX3, —CX2H, —CXH2, —CN, —C(O)N(R)2, —N(R)C(O)R, —N(R)S(O)2R, —N(R)C(O)N(R)2, —N(R)C(S)N(R)2, —CRN(R)2C(O)OR, —N(R)R8, —O(CH2)nOR, —N(R)C(═NR9)N(R)2, —N(R)C(═CHR9)N(R)2, —OC(O)N(R)2, —N(R)C(O)OR, —N(OR)C(O)R, —N(OR)S(O)2R, —N(OR)C(O)OR, —N(OR)C(O)N(R)2, —N(OR)C(S)N(R)2, —N(OR)C(═NR9)N(R)2, —N(OR)C(═CHR9)N(R)2, —C(═NR9)R, —C(O)N(R)OR, and —C(═NR9)N(R)2, and each n is independently selected from 1, 2, 3, 4, and 5;
    • each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′)C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O)(OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;
    • R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • R8 is selected from the group consisting of C3-6 carbocycle and heterocycle;
    • R9 is selected from the group consisting of H, CN, NO2, C1-6 alkyl, —OR, —S(O)2R, —S(O)2N(R)2, C2-6 alkenyl, C3-6 carbocycle and heterocycle;
    • each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;
    • each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;
    • each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;
    • each Y is independently a C3-6 carbocycle;
    • each X is independently selected from the group consisting of F, Cl, Br, and I; and
    • m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
    • or salts or isomers thereof.


In some embodiments, another subset of compounds of Formula (I) includes those in which

    • R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′R′;
    • R2 and R3 are independently selected from the group consisting of H, C2-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;
    • R4 is —(CH2)nQ or —(CH2)·CHQR, where Q is —N(R)2, and n is selected from 3, 4, and 5;
    • each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′)C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O)(OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;
    • R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;
    • each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;
    • each R* is independently selected from the group consisting of C1-12 alkyl and C1-12 alkenyl;
    • each Y is independently a C3-6 carbocycle;
    • each X is independently selected from the group consisting of F, Cl, Br, and I; and
    • m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
    • or salts or isomers thereof.


In some embodiments, another subset of compounds of Formula (I) includes those in which

    • R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′R′;
    • R2 and R3 are independently selected from the group consisting of C1-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;
    • R4 is selected from the group consisting of —(CH2)nQ, —(CH2)nCHQR, —CHQR, and —CQ(R)2, where Q is —N(R)2, and n is selected from 1, 2, 3, 4, and 5;
    • each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′)C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O)(OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;
    • R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
    • each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;
    • each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;
    • each R* is independently selected from the group consisting of C1-12 alkyl and C1-12 alkenyl;
    • each Y is independently a C3-6 carbocycle;
    • each X is independently selected from the group consisting of F, Cl, Br, and I; and
    • m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
    • or salts or isomers thereof.


In some embodiments, a subset of compounds of Formula (I) includes those of Formula (IA):




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    • or a salt or isomer thereof, wherein 1 is selected from 1, 2, 3, 4, and 5; m is selected from 5, 6, 7, 8, and 9; M1 is a bond or M′; R4 is unsubstituted C1-3 alkyl, or —(CH2)nQ, in which Q is OH, —NHC(S)N(R)2, —NHC(O)N(R)2, —N(R)C(O)R, —N(R)S(O)2R, —N(R)R8, —NHC(═NR9)N(R)2, —NHC(═CHR9)N(R)2, —OC(O)N(R)2, —N(R)C(O)OR, heteroaryl or heterocycloalkyl; M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —P(O)(OR′)O—, —S—S—, an aryl group, and a heteroaryl group; and R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, and C2-14 alkenyl.





In some embodiments, a subset of compounds of Formula (I) includes those of Formula (II):




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or a salt or isomer thereof, wherein 1 is selected from 1, 2, 3, 4, and 5; M1 is a bond or M′; R4 is unsubstituted C1-3 alkyl, or —(CH2)nQ, in which n is 2, 3, or 4, and Q is OH, —NHC(S)N(R)2, —NHC(O)N(R)2, —N(R)C(O)R, —N(R)S(O)2R, —N(R)R8, —NHC(═NR9)N(R)2, —NHC(═CHR9)N(R)2, —OC(O)N(R)2, —N(R)C(O)OR, heteroaryl or heterocycloalkyl; M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —P(O)(OR′)O—, —S—S—, an aryl group, and a heteroaryl group; and R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, and C2-14 alkenyl.


In some embodiments, a subset of compounds of Formula (I) includes those of Formula (IIa), (IIb), (IIc), or (IIe):




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    • or a salt or isomer thereof, wherein R4 is as described herein.





In some embodiments, a subset of compounds of Formula (I) includes those of Formula (IId):




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    • or a salt or isomer thereof, wherein n is 2, 3, or 4; and m, R′, R″, and R2 through R6 are as described herein. For example, each of R2 and R3 may be independently selected from the group consisting of C5-14 alkyl and C5-14 alkenyl.





In some embodiments, the compound of Formula (I) is selected from the group consisting of:




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In further embodiments, the compound of Formula (I) is selected from the group consisting of:




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In some embodiments, the compound of Formula (I) is selected from the group consisting of:




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salts and isomers thereof.


In some embodiments, a nanoparticle comprises the following compound:




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or salts and isomers thereof.


In some embodiments, the disclosure features a nanoparticle composition including a lipid component comprising a compound as described herein (e.g., a compound according to Formula (I), (IA), (II), (IIa), (IIb), (IIc), (Hd) or (IIe)).


In some embodiments, the disclosure features a pharmaceutical composition comprising a nanoparticle composition according to the preceding embodiments and a pharmaceutically acceptable carrier. For example, the pharmaceutical composition is refrigerated or frozen for storage and/or shipment (e.g., being stored at a temperature of 4° C. or lower, such as a temperature between about −150° C. and about 0° C. or between about −80° C. and about −20° C. (e.g., about −5° C., −10° C., −15° C., −20° C., −25° C., −30° C., −40° C., −50° C., −60° C., −70° C., −80° C., −90° C., −130° C. or −150° C.). For example, the pharmaceutical composition is a solution that is refrigerated for storage and/or shipment at, for example, about −20° C., −30° C., −40° C., −50° C., −60° C., −70° C., or −80° C.


In some embodiments, the disclosure provides a method of delivering a therapeutic and/or prophylactic (e.g., RNA, such as mRNA) to a cell (e.g., a mammalian cell). This method includes the step of administering to a subject (e.g., a mammal, such as a human) a nanoparticle composition including (i) a lipid component including a phospholipid (such as a polyunsaturated lipid), a PEG lipid, a structural lipid, and a compound of Formula (I), (IA), (II), (IIa), (IIb), (IIc), (IId) or (IIe) and (ii) a therapeutic and/or prophylactic, in which administering involves contacting the cell with the nanoparticle composition, whereby the therapeutic and/or prophylactic is delivered to the cell.


In some embodiments, the disclosure provides a method of producing a polypeptide of interest in a cell (e.g., a mammalian cell). The method includes the step of contacting the cell with a nanoparticle composition including (i) a lipid component including a phospholipid (such as a polyunsaturated lipid), a PEG lipid, a structural lipid, and a compound of Formula (I), (IA), (II), (IIa), (IIb), (IIc), (IId) or (IIe) and (ii) an mRNA encoding the polypeptide of interest, whereby the mRNA is capable of being translated in the cell to produce the polypeptide.


In some embodiments, the disclosure provides a method of treating a disease or disorder in a mammal (e.g., a human) in need thereof. The method includes the step of administering to the mammal a therapeutically effective amount of a nanoparticle composition including (i) a lipid component including a phospholipid (such as a polyunsaturated lipid), a PEG lipid, a structural lipid, and a compound of Formula (I), (IA), (II), (IIa), (IIb), (IIc), (IId) or (IIe) and (ii) a therapeutic and/or prophylactic (e.g., an mRNA).


In some embodiments, the disease or disorder is characterized by dysfunctional or aberrant protein or polypeptide activity. For example, the disease or disorder is selected from the group consisting of rare diseases, infectious diseases, cancer and proliferative diseases, genetic diseases (e.g., cystic fibrosis), autoimmune diseases, diabetes, neurodegenerative diseases, cardio- and reno-vascular diseases, and metabolic diseases.


In some embodiments, the disclosure provides a method of delivering (e.g., specifically delivering) a therapeutic and/or prophylactic to a mammalian organ (e.g., a liver, spleen, lung, or femur). This method includes the step of administering to a subject (e.g., a mammal) a nanoparticle composition including (i) a lipid component including a phospholipid, a PEG lipid, a structural lipid, and a compound of Formula (I), (IA), (II), (IIa), (IIb), (IIc), (IId) or (He) and (ii) a therapeutic and/or prophylactic (e.g., an mRNA), in which administering involves contacting the cell with the nanoparticle composition, whereby the therapeutic and/or prophylactic is delivered to the target organ (e.g., a liver, spleen, lung, or femur).


In some embodiments, the disclosure features a method for the enhanced delivery of a therapeutic and/or prophylactic (e.g., an mRNA) to a target tissue (e.g., a liver, spleen, lung, or femur). This method includes administering to a subject (e.g., a mammal) a nanoparticle composition, the composition including (i) a lipid component including a compound of Formula (I), (IA), (II), (IIa), (IIb), (Tic), (lid) or (He), a phospholipid, a structural lipid, and a PEG lipid; and (ii) a therapeutic and/or prophylactic, the administering including contacting the target tissue with the nanoparticle composition, whereby the therapeutic and/or prophylactic is delivered to the target tissue.


In some embodiments, the disclosure features a method of lowering immunogenicity comprising introducing the nanoparticle composition of the disclosure into cells, wherein the nanoparticle composition reduces the induction of the cellular immune response of the cells to the nanoparticle composition, as compared to the induction of the cellular immune response in cells induced by a reference composition which comprises a reference lipid instead of a compound of Formula (I), (IA), (II), (IIa), (IIb), (IIc), (IId) or (IIe). For example, the cellular immune response is an innate immune response, an adaptive immune response, or both.


The disclosure also includes methods of synthesizing a compound of Formula (I), (IA), (II), (IIa), (IIb), (IIc), (IId) or (IIe) and methods of making a nanoparticle composition including a lipid component comprising the compound of Formula (I), (IA), (II), (IIa), (IIb), (IIc), (IId) or (IIe)


Modes of Vaccine Administration

Influenza RNA (e.g. mRNA) vaccines may be administered by any route which results in a therapeutically effective outcome. These include, but are not limited, to intradermal, intramuscular, intranasal and/or subcutaneous administration. The present disclosure provides methods comprising administering RNA (e.g., mRNA) vaccines to a subject in need thereof. The exact amount required will vary from subject to subject, depending on the species, age, and general condition of the subject, the severity of the disease, the particular composition, its mode of administration, its mode of activity, and the like. Influenza RNA (e.g., mRNA) vaccines compositions are typically formulated in dosage unit form for ease of administration and uniformity of dosage. It will be understood, however, that the total daily usage of RNA (e.g., mRNA) vaccine compositions may be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective, prophylactically effective, or appropriate imaging dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed; and like factors well known in the medical arts.


In some embodiments, influenza disease RNA (e.g. mRNA) vaccines compositions may be administered at dosage levels sufficient to deliver 0.0001 mg/kg to 100 mg/kg, 0.001 mg/kg to 0.05 mg/kg, 0.005 mg/kg to 0.05 mg/kg, 0.001 mg/kg to 0.005 mg/kg, 0.05 mg/kg to 0.5 mg/kg, 0.01 mg/kg to 50 mg/kg, 0.1 mg/kg to 40 mg/kg, 0.5 mg/kg to 30 mg/kg, 0.01 mg/kg to 10 mg/kg, 0.1 mg/kg to 10 mg/kg, or 1 mg/kg to 25 mg/kg, of subject body weight per day, one or more times a day, per week, per month, etc. to obtain the desired therapeutic, diagnostic, prophylactic, or imaging effect (see, e.g., the range of unit doses described in International Publication No WO2013/078199, the contents of which are herein incorporated by reference in their entirety). The desired dosage may be delivered three times a day, two times a day, once a day, every other day, every third day, every week, every two weeks, every three weeks, every four weeks, every 2 months, every three months, every 6 months, etc. In some embodiments, the desired dosage may be delivered using multiple administrations (e.g., two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, or more administrations). When multiple administrations are employed, split dosing regimens such as those described herein may be used. In exemplary embodiments, influenza RNA (e.g., mRNA) vaccines compositions may be administered at dosage levels sufficient to deliver 0.0005 mg/kg to 0.01 mg/kg, e.g., about 0.0005 mg/kg to about 0.0075 mg/kg, e.g., about 0.0005 mg/kg, about 0.001 mg/kg, about 0.002 mg/kg, about 0.003 mg/kg, about 0.004 mg/kg or about 0.005 mg/kg.


In some embodiments, influenza disease RNA (e.g., mRNA) vaccine compositions may be administered once or twice (or more) at dosage levels sufficient to deliver 0.025 mg/kg to 0.250 mg/kg, 0.025 mg/kg to 0.500 mg/kg, 0.025 mg/kg to 0.750 mg/kg, or 0.025 mg/kg to 1.0 mg/kg.


In some embodiments, influenza disease RNA (e.g., mRNA) vaccine compositions may be administered twice (e.g., Day 0 and Day 7, Day 0 and Day 14, Day 0 and Day 21, Day 0 and Day 28, Day 0 and Day 60, Day 0 and Day 90, Day 0 and Day 120, Day 0 and Day 150, Day 0 and Day 180, Day 0 and 3 months later, Day 0 and 6 months later, Day 0 and 9 months later, Day 0 and 12 months later, Day 0 and 18 months later, Day 0 and 2 years later, Day 0 and 5 years later, or Day 0 and 10 years later) at a total dose of or at dosage levels sufficient to deliver a total dose of 0.0100 mg, 0.025 mg, 0.050 mg, 0.075 mg, 0.100 mg, 0.125 mg, 0.150 mg, 0.175 mg, 0.200 mg, 0.225 mg, 0.250 mg, 0.275 mg, 0.300 mg, 0.325 mg, 0.350 mg, 0.375 mg, 0.400 mg, 0.425 mg, 0.450 mg, 0.475 mg, 0.500 mg, 0.525 mg, 0.550 mg, 0.575 mg, 0.600 mg, 0.625 mg, 0.650 mg, 0.675 mg, 0.700 mg, 0.725 mg, 0.750 mg, 0.775 mg, 0.800 mg, 0.825 mg, 0.850 mg, 0.875 mg, 0.900 mg, 0.925 mg, 0.950 mg, 0.975 mg, or 1.0 mg. Higher and lower dosages and frequency of administration are encompassed by the present disclosure. For example, an influenza RNA (e.g., mRNA) vaccine composition may be administered three or four times.


In some embodiments, influenza RNA (e.g., mRNA) vaccine compositions may be administered twice (e.g., Day 0 and Day 7, Day 0 and Day 14, Day 0 and Day 21, Day 0 and Day 28, Day 0 and Day 60, Day 0 and Day 90, Day 0 and Day 120, Day 0 and Day 150, Day 0 and Day 180, Day 0 and 3 months later, Day 0 and 6 months later, Day 0 and 9 months later, Day 0 and 12 months later, Day 0 and 18 months later, Day 0 and 2 years later, Day 0 and 5 years later, or Day 0 and 10 years later) at a total dose of or at dosage levels sufficient to deliver a total dose of 0.010 mg, 0.025 mg, 0.100 mg or 0.400 mg.


In some embodiments, the influenza RNA (e.g., mRNA) vaccine for use in a method of vaccinating a subject is administered to the subject as a single dosage of between 10 μg/kg and 400 μg/kg of the nucleic acid vaccine (in an effective amount to vaccinate the subject). In some embodiments the RNA (e.g., mRNA) vaccine for use in a method of vaccinating a subject is administered to the subject as a single dosage of between 10 μg and 400 μg of the nucleic acid vaccine (in an effective amount to vaccinate the subject). In some embodiments, an influenza RNA (e.g., mRNA) vaccine for use in a method of vaccinating a subject is administered to the subject as a single dosage of 25-1000 μg. In some embodiments, an influenza RNA (e.g., mRNA) vaccine is administered to the subject as a single dosage of 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950 or 1000 μg. For example, an influenza RNA (e.g., mRNA) vaccine may be administered to a subject as a single dose of 25-100, 25-500, 50-100, 50-500, 50-1000, 100-500, 100-1000, 250-500, 250-1000, or 500-1000 μg. In some embodiments, an influenza RNA (e.g., mRNA) vaccine for use in a method of vaccinating a subject is administered to the subject as two dosages, the combination of which equals 25-1000 μg of the influenza RNA (e.g., mRNA) vaccine.


An influenza RNA (e.g. mRNA) vaccine pharmaceutical composition described herein can be formulated into a dosage form described herein, such as an intranasal, intratracheal, or injectable (e.g., intravenous, intraocular, intravitreal, intramuscular, intradermal, intracardiac, intraperitoneal, intranasal and subcutaneous).


Influenza Virus RNA (e.g., mRNA) Vaccine Formulations and Methods of Use


Some aspects of the present disclosure provide formulations of the influenza RNA (e.g., mRNA) vaccine, wherein the RNA (e.g., mRNA) vaccine is formulated in an effective amount to produce an antigen specific immune response in a subject (e.g., production of antibodies specific to an influenza antigenic polypeptide). “An effective amount” is a dose of an RNA (e.g., mRNA) vaccine effective to produce an antigen-specific immune response. Also provided herein are methods of inducing an antigen-specific immune response in a subject.


In some embodiments, the antigen-specific immune response is characterized by measuring an anti-influenza antigenic polypeptide antibody titer produced in a subject administered an influenza RNA (e.g., mRNA) vaccine as provided herein. An antibody titer is a measurement of the amount of antibodies within a subject, for example, antibodies that are specific to a particular antigen (e.g., an influenza antigenic polypeptide) or epitope of an antigen. Antibody titer is typically expressed as the inverse of the greatest dilution that provides a positive result. Enzyme-linked immunosorbent assay (ELISA) is a common assay for determining antibody titers, for example.


In some embodiments, an antibody titer is used to assess whether a subject has had an infection or to determine whether immunizations are required. In some embodiments, an antibody titer is used to determine the strength of an autoimmune response, to determine whether a booster immunization is needed, to determine whether a previous vaccine was effective, and to identify any recent or prior infections. In accordance with the present disclosure, an antibody titer may be used to determine the strength of an immune response induced in a subject by the influenza RNA (e.g., mRNA) vaccine.


In some embodiments, an anti-influenza antigenic polypeptide antibody titer produced in a subject is increased by at least 1 log relative to a control. For example, anti-antigenic polypeptide antibody titer produced in a subject may be increased by at least 1.5, at least 2, at least 2.5, or at least 3 log relative to a control. In some embodiments, the anti-antigenic polypeptide antibody titer produced in the subject is increased by 1, 1.5, 2, 2.5 or 3 log relative to a control. In some embodiments, the anti-antigenic polypeptide antibody titer produced in the subject is increased by 1-3 log relative to a control. For example, the anti-antigenic polypeptide antibody titer produced in a subject may be increased by 1-1.5, 1-2, 1-2.5, 1-3, 1.5-2, 1.5-2.5, 1.5-3, 2-2.5, 2-3, or 2.5-3 log relative to a control.


In some embodiments, the anti-influenza antigenic polypeptide antibody titer produced in a subject is increased at least 2 times relative to a control. For example, the anti-antigenic polypeptide antibody titer produced in a subject may be increased at least 3 times, at least 4 times, at least 5 times, at least 6 times, at least 7 times, at least 8 times, at least 9 times, or at least 10 times relative to a control. In some embodiments, the anti-antigenic polypeptide antibody titer produced in the subject is increased 2, 3, 4, 5,6, 7, 8, 9, or 10 times relative to a control. In some embodiments, the anti-antigenic polypeptide antibody titer produced in a subject is increased 2-10 times relative to a control. For example, the anti-antigenic polypeptide antibody titer produced in a subject may be increased 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10, 5-9, 5-8, 5-7, 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8-10, 8-9, or 9-10 times relative to a control.


A control, in some embodiments, is the anti-influenza antigenic polypeptide antibody titer produced in a subject who has not been administered an influenza RNA (e.g., mRNA) vaccine of the present disclosure. In some embodiments, a control is an anti-influenza antigenic polypeptide antibody titer produced in a subject who has been administered a live attenuated influenza vaccine. An attenuated vaccine is a vaccine produced by reducing the virulence of a viable (live). An attenuated virus is altered in a manner that renders it harmless or less virulent relative to live, unmodified virus. In some embodiments, a control is an anti-influenza antigenic polypeptide antibody titer produced in a subject administered inactivated influenza vaccine. In some embodiments, a control is an anti-influenza antigenic polypeptide antibody titer produced in a subject administered a recombinant or purified influenza protein vaccine. Recombinant protein vaccines typically include protein antigens that either have been produced in a heterologous expression system (e.g., bacteria or yeast) or purified from large amounts of the pathogenic organism. In some embodiments, a control is an anti-influenza antigenic polypeptide antibody titer produced in a subject who has been administered an influenza virus-like particle (VLP) vaccine.


In some embodiments, an effective amount of an influenza RNA (e.g., mRNA) vaccine is a dose that is reduced compared to the standard of care dose of a recombinant influenza protein vaccine. A “standard of care,” as provided herein, refers to a medical or psychological treatment guideline and can be general or specific. “Standard of care” specifies appropriate treatment based on scientific evidence and collaboration between medical professionals involved in the treatment of a given condition. It is the diagnostic and treatment process that a physician/clinician should follow for a certain type of patient, illness or clinical circumstance. A “standard of care dose,” as provided herein, refers to the dose of a recombinant or purified influenza protein vaccine, or a live attenuated or inactivated influenza vaccine, that a physician/clinician or other medical professional would administer to a subject to treat or prevent influenza, or a related condition, while following the standard of care guideline for treating or preventing influenza, or a related condition.


In some embodiments, the anti-influenza antigenic polypeptide antibody titer produced in a subject administered an effective amount of an influenza RNA (e.g., mRNA) vaccine is equivalent to an anti-influenza antigenic polypeptide antibody titer produced in a control subject administered a standard of care dose of a recombinant or purified influenza protein vaccine or a live attenuated or inactivated influenza vaccine.


In some embodiments, an effective amount of an influenza RNA (e.g., mRNA) vaccine is a dose equivalent to an at least 2-fold reduction in a standard of care dose of a recombinant or purified influenza protein vaccine. For example, an effective amount of an influenza RNA (e.g., mRNA) vaccine may be a dose equivalent to an at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, or at least 10-fold reduction in a standard of care dose of a recombinant or purified influenza protein vaccine. In some embodiments, an effective amount of an influenza RNA (e.g., mRNA) vaccine is a dose equivalent to an at least at least 100-fold, at least 500-fold, or at least 1000-fold reduction in a standard of care dose of a recombinant or purified influenza protein vaccine. In some embodiments, an effective amount of an influenza RNA (e.g., mRNA) vaccine is a dose equivalent to a 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 20-, 50-, 100-, 250-, 500-, or 1000-fold reduction in a standard of care dose of a recombinant or purified influenza protein vaccine. In some embodiments, the anti-influenza antigenic polypeptide antibody titer produced in a subject administered an effective amount of an influenza RNA (e.g., mRNA) vaccine is equivalent to an anti-influenza antigenic polypeptide antibody titer produced in a control subject administered the standard of care dose of a recombinant or protein influenza protein vaccine or a live attenuated or inactivated influenza vaccine. In some embodiments, an effective amount of an influenza RNA (e.g., mRNA) vaccine is a dose equivalent to a 2-fold to 1000-fold (e.g., 2-fold to 100-fold, 10-fold to 1000-fold) reduction in the standard of care dose of a recombinant or purified influenza protein vaccine, wherein the anti-influenza antigenic polypeptide antibody titer produced in the subject is equivalent to an anti-influenza antigenic polypeptide antibody titer produced in a control subject administered the standard of care dose of a recombinant or purified influenza protein vaccine or a live attenuated or inactivated influenza vaccine.


In some embodiments, the effective amount of an influenza RNA (e.g., mRNA) vaccine is a dose equivalent to a 2 to 1000-, 2 to 900-, 2 to 800-, 2 to 700-, 2 to 600-, 2 to 500-, 2 to 400-, 2 to 300-, 2 to 200-, 2 to 100-, 2 to 90-, 2 to 80-, 2 to 70-, 2 to 60-, 2 to 50-, 2 to 40-, 2 to 30-, 2 to 20-, 2 to 10-, 2 to 9-, 2 to 8-, 2 to 7-, 2 to 6-, 2 to 5-, 2 to 4-, 2 to 3-, 3 to 1000-, 3 to 900-, 3 to 800-, 3 to 700-, 3 to 600-, 3 to 500-, 3 to 400-, 3 to 3 to 00-, 3 to 200-, 3 to 100-, 3 to 90-, 3 to 80-, 3 to 70-, 3 to 60-, 3 to 50-, 3 to 40-, 3 to 30-, 3 to 20-, 3 to 10-, 3 to 9-, 3 to 8-, 3 to 7-, 3 to 6-, 3 to 5-, 3 to 4-, 4 to 1000-, 4 to 900-, 4 to 800-, 4 to 700-, 4 to 600-, 4 to 500-, 4 to 400-, 4 to 300-, 4 to 200-, 4 to 100-, 4 to 90-, 4 to 80-, 4 to 70-, 4 to 60-, 4 to 50-, 4 to 40-, 4 to 30-, 4 to 20-, 4 to 10-, 4 to 9-, 4 to 8-, 4 to 7-, 4 to 6-, 4 to 5-, 4 to 4-, 5 to 1000-, 5 to 900-, 5 to 800-, 5 to 700-, 5 to 600-, 5 to 500-, 5 to 400-, 5 to 300-, 5 to 200-, 5 to 100-, 5 to 90-, 5 to 80-, 5 to 70-, 5 to 60-, 5 to 50-, 5 to 40-, 5 to 30-, 5 to 20-, 5 to 10-, 5 to 9-, 5 to 8-, 5 to 7-, 5 to 6-, 6 to 1000-, 6 to 900-, 6 to 800-, 6 to 700-, 6 to 600-, 6 to 500-, 6 to 400-, 6 to 300-, 6 to 200-, 6 to 100-, 6 to 90-, 6 to 80-, 6 to 70-, 6 to 60-, 6 to 50-, 6 to 40-, 6 to 30-, 6 to 20-, 6 to 10-, 6 to 9-, 6 to 8-, 6 to 7-, 7 to 1000-, 7 to 900-, 7 to 800-, 7 to 700-, 7 to 600-, 7 to 500-, 7 to 400-, 7 to 300-, 7 to 200-, 7 to 100-, 7 to 90-, 7 to 80-, 7 to 70-, 7 to 60-, 7 to 50-, 7 to 40-, 7 to 30-, 7 to 20-, 7 to 10-, 7 to 9-, 7 to 8-, 8 to 1000-, 8 to 900-, 8 to 800-, 8 to 700-, 8 to 600-, 8 to 500-, 8 to 400-, 8 to 300-, 8 to 200-, 8 to 100-, 8 to 90-, 8 to 80-, 8 to 70-, 8 to 60-, 8 to 50-, 8 to 40-, 8 to 30-, 8 to 20-, 8 to 10-, 8 to 9-, 9 to 1000-, 9 to 900-, 9 to 800-, 9 to 700-, 9 to 600-, 9 to 500-, 9 to 400-, 9 to 300-, 9 to 200-, 9 to 100-, 9 to 90-, 9 to 80-, 9 to 70-, 9 to 60-, 9 to 50-, 9 to 40-, 9 to 30-, 9 to 20-, 9 to 10-, 10 to 1000-, 10 to 900-, 10 to 800-, 10 to 700-, 10 to 600-, 10 to 500-, 10 to 400-, 10 to 300-, 10 to 200-, 10 to 100-, 10 to 90-, 10 to 80-, 10 to 70-, 10 to 60-, 10 to 50-, 10 to 40-, 10 to 30-, 10 to 20-, 20 to 1000-, 20 to 900-, 20 to 800-, 20 to 700-, 20 to 600-, 20 to 500-, 20 to 400-, 20 to 300-, 20 to 200-, 20 to 100-, 20 to 90-, 20 to 80-, 20 to 70-, 20 to 60-, 20 to 50-, 20 to 40-, 20 to 30-, 30 to 1000-, 30 to 900-, 30 to 800-, 30 to 700-, 30 to 600-, 30 to 500-, 30 to 400-, 30 to 300-, 30 to 200-, 30 to 100-, 30 to 90-, 30 to 80-, 30 to 70-, 30 to 60-, 30 to 50-, 30 to 40-, 40 to 1000-, 40 to 900-, 40 to 800-, 40 to 700-, 40 to 600-, 40 to 500-, 40 to 400-, 40 to 300-, 40 to 200-, 40 to 100-, 40 to 90-, 40 to 80-, 40 to 70-, 40 to 60-, 40 to 50-, 50 to 1000-, 50 to 900-, 50 to 800-, 50 to 700-, 50 to 600-, 50 to 500-, 50 to 400-, 50 to 300-, 50 to 200-, 50 to 100-, 50 to 90-, 50 to 80-, 50 to 70-, 50 to 60-, 60 to 1000-, 60 to 900-, 60 to 800-, 60 to 700-, 60 to 600-, 60 to 500-, 60 to 400-, 60 to 300-, 60 to 200-, 60 to 100-, 60 to 90-, 60 to 80-, 60 to 70-, 70 to 1000-, 70 to 900-, 70 to 800-, 70 to 700-, 70 to 600-, 70 to 500-, 70 to 400-, 70 to 300-, 70 to 200-, 70 to 100-, 70 to 90-, 70 to 80-, 80 to 1000-, 80 to 900-, 80 to 800-, 80 to 700-, 80 to 600-, 80 to 500-, 80 to 400-, 80 to 300-, 80 to 200-, 80 to 100-, 80 to 90-, 90 to 1000-, 90 to 900-, 90 to 800-, 90 to 700-, 90 to 600-, 90 to 500-, 90 to 400-, 90 to 300-, 90 to 200-, 90 to 100-, 100 to 1000-, 100 to 900-, 100 to 800-, 100 to 700-, 100 to 600-, 100 to 500-, 100 to 400-, 100 to 300-, 100 to 200-, 200 to 1000-, 200 to 900-, 200 to 800-, 200 to 700-, 200 to 600-, 200 to 500-, 200 to 400-, 200 to 300-, 300 to 1000-, 300 to 900-, 300 to 800-, 300 to 700-, 300 to 600-, 300 to 500-, 300 to 400-, 400 to 1000-, 400 to 900-, 400 to 800-, 400 to 700-, 400 to 600-, 400 to 500-, 500 to 1000-, 500 to 900-, 500 to 800-, 500 to 700-, 500 to 600-, 600 to 1000-, 600 to 900-, 600 to 800-, 600 to 700-, 700 to 1000-, 700 to 900-, 700 to 800-, 800 to 1000-, 800 to 900-, or 900 to 1000-fold reduction in the standard of care dose of a recombinant influenza protein vaccine. In some embodiments, the anti-antigenic polypeptide antibody titer produced in the subject is equivalent to an anti-antigenic polypeptide antibody titer produced in a control subject administered the standard of care dose of a recombinant or purified influenza protein vaccine or a live attenuated or inactivated influenza vaccine. In some embodiments, the effective amount is a dose equivalent to (or equivalent to an at least) 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 20-, 30-, 40-, 50-, 60-, 70-, 80-, 90-, 100-, 110-, 120-, 130-, 140-, 150-, 160-, 170-, 1280-, 190-, 200-, 210-, 220-, 230-, 240-, 250-, 260-, 270-, 280-, 290-, 300-, 310-, 320-, 330-, 340-, 350-, 360-, 370-, 380-, 390-, 400-, 410-, 420-, 430-, 440-, 450-, 4360-, 470-, 480-, 490-, 500-, 510-, 520-, 530-, 540-, 550-, 560-, 5760-, 580-, 590-, 600-, 610-, 620-, 630-, 640-, 650-, 660-, 670-, 680-, 690-, 700-, 710-, 720-, 730-, 740-, 750-, 760-, 770-, 780-, 790-, 800-, 810-, 820-, 830-, 840-, 850-, 860-, 870-, 880-, 890-, 900-, 910-, 920-, 930-, 940-, 950-, 960-, 970-, 980-, 990-, or 1000-fold reduction in the standard of care dose of a recombinant influenza protein vaccine. In some embodiments, an anti-antigenic polypeptide antibody titer produced in the subject is equivalent to an anti-antigenic polypeptide antibody titer produced in a control subject administered the standard of care dose of a recombinant or purified influenza protein vaccine or a live attenuated or inactivated an influenza vaccine.


In some embodiments, the effective amount of an influenza RNA (e.g., mRNA) vaccine is a total dose of 50-1000 μg. In some embodiments, the effective amount of an influenza RNA (e.g., mRNA) vaccine is a total dose of 50-1000, 50-900, 50-800, 50-700, 50-600, 50-500, 50-400, 50-300, 50-200, 50-100, 50-90, 50-80, 50-70, 50-60, 60-1000, 60-900, 60-800, 60-700, 60-600, 60-500, 60-400, 60-300, 60-200, 60-100, 60-90, 60-80, 60-70, 70-1000, 70-900, 70-800, 70-700, 70-600, 70-500, 70-400, 70-300, 70-200, 70-100, 70-90, 70-80, 80-1000, 80-900, 80-800, 80-700, 80-600, 80-500, 80-400, 80-300, 80-200, 80-100, 80-90, 90-1000, 90-900, 90-800, 90-700, 90-600, 90-500, 90-400, 90-300, 90-200, 90-100, 100-1000, 100-900, 100-800, 100-700, 100-600, 100-500, 100-400, 100-300, 100-200, 200-1000, 200-900, 200-800, 200-700, 200-600, 200-500, 200-400, 200-300, 300-1000, 300-900, 300-800, 300-700, 300-600, 300-500, 300-400, 400-1000, 400-900, 400-800, 400-700, 400-600, 400-500, 500-1000, 500-900, 500-800, 500-700, 500-600, 600-1000, 600-900, 600-900, 600-700, 700-1000, 700-900, 700-800, 800-1000, 800-900, or 900-1000 μg. In some embodiments, the effective amount of an influenza RNA (e.g., mRNA) vaccine is a total dose of 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950 or 1000 μg. In some embodiments, the effective amount is a dose of 25-500 μg administered to the subject a total of two times. In some embodiments, the effective amount of an influenza RNA (e.g., mRNA) vaccine is a dose of 25-500, 25-400, 25-300, 25-200, 25-100, 25-50, 50-500, 50-400, 50-300, 50-200, 50-100, 100-500, 100-400, 100-300, 100-200, 150-500, 150-400, 150-300, 150-200, 200-500, 200-400, 200-300, 250-500, 250-400, 250-300, 300-500, 300-400, 350-500, 350-400, 400-500 or 450-500 μg administered to the subject a total of two times. In some embodiments, the effective amount of an influenza RNA (e.g., mRNA) vaccine is a total dose of 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 μg administered to the subject a total of two times.


Additional Embodiments





    • 1. An influenza virus vaccine or composition or immunogenic composition, comprising:
      • at least one messenger ribonucleic acid (mRNA) polynucleotide having a 5′ terminal cap, an open reading frame encoding at least one influenza antigenic polypeptide, and a 3′ polyA tail.

    • 2. The vaccine of paragraph 1, wherein the at least one mRNA polynucleotide is encoded by a sequence identified by SEQ ID NO: 447-457, 459, 461, 505-523, or 570-573.

    • 3. The vaccine of paragraph 1, wherein the at least one mRNA polynucleotide comprises a sequence identified by SEQ ID NO: 491-503, 524-542, or 566-569.

    • 4. The vaccine of paragraph 1, wherein the at least one antigenic polypeptide comprises a sequence identified by SEQ ID NO: 1-444, 458, 460, 462-479, or 543-565.

    • 5. The vaccine of paragraph 1, wherein the at least one mRNA polynucleotide is encoded by a sequence identified by SEQ ID NO: 457.

    • 6. The vaccine of paragraph 1, wherein the at least one mRNA polynucleotide comprises a sequence identified by SEQ ID NO: 501.

    • 7. The vaccine of paragraph 1, wherein the at least one antigenic polypeptide comprises a sequence identified by SEQ ID NO: 458.

    • 8. The vaccine of paragraph 1, wherein the at least one mRNA polynucleotide is encoded by a sequence identified by SEQ ID NO: 459.

    • 9. The vaccine of paragraph 1, wherein the at least one mRNA polynucleotide comprises a sequence identified by SEQ ID NO: 502.

    • 10. The vaccine of paragraph 1, wherein the at least one antigenic polypeptide comprises a sequence identified by SEQ ID NO: 460.

    • 11. The vaccine of paragraph 1, wherein the at least one mRNA polynucleotide is encoded by a sequence identified by SEQ ID NO: 461.

    • 12. The vaccine of paragraph 1, wherein the at least one mRNA polynucleotide comprises a sequence identified by SEQ ID NO: 503.

    • 13. The vaccine of paragraph 1, wherein the at least one antigenic polypeptide comprises a sequence identified by SEQ ID NO: 462.

    • 14. The vaccine of any one of paragraphs 1-13, wherein the 5′ terminal cap is or comprises 7mG(5′)ppp(5′)NlmpNp.

    • 15. The vaccine of any one of paragraphs 1-14, wherein 100% of the uracil in the open reading frame is modified to include N1-methyl pseudouridine at the 5-position of the uracil.

    • 16. The vaccine of any one of paragraphs 1-15, wherein the vaccine is formulated in a lipid nanoparticle comprising: DLin-MC3-DMA; cholesterol; 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC); and polyethylene glycol (PEG)2000-DMG.

    • 17. The vaccine of paragraph 16, wherein the lipid nanoparticle further comprises trisodium citrate buffer, sucrose and water.

    • 18. A influenza virus vaccine or composition or immunogenic composition, comprising:
      • at least one messenger ribonucleic acid (mRNA) polynucleotide having a 5′ terminal cap 7mG(5′)ppp(5′)NlmpNp, a sequence identified by SEQ ID NO: 501 and a 3′ polyA tail, wherein the uracil nucleotides of the sequence identified by SEQ ID NO: 501 are modified to include N1-methyl pseudouridine at the 5-position of the uracil nucleotide.

    • 19. A influenza virus vaccine, comprising:
      • at least one messenger ribonucleic acid (mRNA) polynucleotide having a 5′ terminal cap 7mG(5′)ppp(5′)NlmpNp, a sequence identified by SEQ ID NO: 502 and a 3′ polyA tail, wherein the uracil nucleotides of the sequence identified by SEQ ID NO: 502 are modified to include N1-methyl pseudouridine at the 5-position of the uracil nucleotide.

    • 20. A influenza virus vaccine or composition or immunogenic composition, comprising:
      • at least one messenger ribonucleic acid (mRNA) polynucleotide having a 5′ terminal cap 7mG(5′)ppp(5′)NlmpNp, a sequence identified by SEQ ID NO: 503 and a 3′ polyA tail, wherein the uracil nucleotides of the sequence identified by SEQ ID NO: 503 are modified to include N1-methyl pseudouridine at the 5-position of the uracil nucleotide.

    • 21. The vaccine of any one of paragraphs 18-20 formulated in a lipid nanoparticle comprising DLin-MC3-DMA, cholesterol, 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC), and polyethylene glycol (PEG)2000-DMG.

    • 22. The vaccine of any one of paragraphs 1-21 formulated in a lipid nanoparticle comprising at least one cationic lipid selected from compounds of Formula (I):







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    • or a salt or isomer thereof, wherein:

    • R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, R*YR″, YR″, and R″M′R′;

    • R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, C2-14 alkenyl, R*YR″, YR″, and R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;

    • R4 is selected from the group consisting of a C3-6 carbocycle, (CH2)nQ, (CH2)nCHQR, CHQR, CQ(R)2, and unsubstituted C1-6 alkyl, where Q is selected from a carbocycle, heterocycle, —OR, —O(CH2)nN(R)2, C(O)OR, —OC(O)R, CX3, CX2H, CXH2, CN, N(R)2, C(O)N(R)2, N(R)C(O)R, N(R)S(O)2R, N(R)C(O)N(R)2, N(R)C(S)N(R)2, N(R)R8, O(CH2)nOR, N(R)C(═NR9)N(R)2, N(R)C(═CHR9)N(R)2, OC(O)N(R)2, N(R)C(O)OR, N(OR)C(O)R, N(OR)S(O)2R, N(OR)C(O)OR, N(OR)C(O)N(R)2, N(OR)C(S)N(R)2, N(OR)C(═NR9)N(R)2, N(OR)C(═CHR9)N(R)2, C(═NR9)N(R)2, C(═NR9)R, C(O)N(R)OR, and —C(R)N(R)2C(O)OR, and each n is independently selected from 1, 2, 3, 4, and 5;

    • each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • M and M′ are independently selected from C(O)O, OC(O), C(O)N(R′), N(R′)C(O), C(O), C(S), C(S)S, SC(S), CH(OH), P(0)(OR′)O, S(O)2, S, an aryl group, and a heteroaryl group;

    • R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • R8 is selected from the group consisting of C3-6 carbocycle and heterocycle;

    • R9 is selected from the group consisting of H, CN, NO2, C1-6 alkyl, —OR, —S(O)2R, —S(O)2N(R)2, C2-6 alkenyl, C3-6 carbocycle and heterocycle;

    • each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, R*YR″, YR″, and H;

    • each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;

    • each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;

    • each Y is independently a C3-6 carbocycle;

    • each X is independently selected from the group consisting of F, Cl, Br, and I; and

    • m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.

    • 23. The vaccine of paragraph 22, wherein a subset of compounds of Formula (I) includes those in which when R4 is (CH2)nQ, (CH2)nCHQR, —CHQR, or CQ(R)2, then (i) Q is not N(R)2 when n is 1, 2, 3, 4 or 5, or (ii) Q is not 5, 6, or 7-membered heterocycloalkyl when n is 1 or 2.

    • 24. The vaccine of paragraph 22, wherein a subset of compounds of Formula (I) includes those in which

    • R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, R*YR″, YR″, and R″M′R′;

    • R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, C2-14 alkenyl, R*YR″, YR″, and R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;

    • R4 is selected from the group consisting of a C3-6 carbocycle, (CH2)nQ, (CH2)nCHQR, CHQR, CQ(R)2, and unsubstituted C1-6 alkyl, where Q is selected from a C3-6 carbocycle, a 5- to 14-membered heteroaryl having one or more heteroatoms selected from N, O, and S, —OR, —O(CH2)nN(R)2, C(O)OR, —OC(O)R, CX3, CX2H, CXH2, CN, C(O)N(R)2, N(R)C(O)R, N(R)S(O)2R, N(R)C(O)N(R)2, N(R)C(S)N(R)2, CRN(R)2C(O)OR, N(R)R8, O(CH2)nOR, N(R)C(═NR9)N(R)2, N(R)C(═CHR9)N(R)2, OC(O)N(R)2, N(R)C(O)OR, N(OR)C(O)R, N(OR)S(O)2R, N(OR)C(O)OR, N(OR)C(O)N(R)2, N(OR)C(S)N(R)2, N(OR)C(═NR9)N(R)2, N(OR)C(═CHR9)N(R)2, C(═NR9)N(R)2, C(═NR9)R, C(O)N(R)OR, and a 5- to 14-membered heterocycloalkyl having one or more heteroatoms selected from N, O, and S which is substituted with one or more substituents selected from oxo (═O), OH, amino, mono- or di-alkylamino, and C1-3 alkyl, and each n is independently selected from 1, 2, 3, 4, and 5;

    • each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • M and M′ are independently selected from C(O)O, OC(O), C(O)N(R′), N(R′)C(O), C(O), C(S), C(S)S, SC(S), CH(OH), P(0)(OR′)O, S(O)2, S, an aryl group, and a heteroaryl group;

    • R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • R8 is selected from the group consisting of C3-6 carbocycle and heterocycle;

    • R9 is selected from the group consisting of H, CN, NO2, C1-6 alkyl, —OR, —S(O)2R,

    • —S(O)2N(R)2, C2-6 alkenyl, C3-6 carbocycle and heterocycle;

    • each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, R*YR″, YR″, and H;

    • each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;

    • each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;

    • each Y is independently a C3-6 carbocycle;

    • each X is independently selected from the group consisting of F, Cl, Br, and I; and

    • m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,

    • or salts or isomers thereof.

    • 25. The vaccine of paragraph 22, wherein a subset of compounds of Formula (I) includes those in which

    • R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, R*YR″, YR″, and R″M′R′;

    • R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, C2-14 alkenyl, R*YR″, YR″, and R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;

    • R4 is selected from the group consisting of a C3-6 carbocycle, (CH2)nQ, (CH2)nCHQR, CHQR, CQ(R)2, and unsubstituted C1-6 alkyl, where Q is selected from a C3-6 carbocycle, a 5- to 14-membered heterocycle having one or more heteroatoms selected from N, O, and S, —OR, —O(CH2)nN(R)2, C(O)OR, —OC(O)R, CX3, CX2H, CXH2, CN, C(O)N(R)2, N(R)C(O)R, N(R)S(O)2R, N(R)C(O)N(R)2, N(R)C(S)N(R)2, CRN(R)2C(O)OR, N(R)R8, O(CH2)nOR, N(R)C(═NR9)N(R)2, N(R)C(═CHR9)N(R)2, OC(O)N(R)2, N(R)C(O)OR, N(OR)C(O)R, N(OR)S(O)2R, N(OR)C(O)OR, N(OR)C(O)N(R)2, N(OR)C(S)N(R)2, N(OR)C(═NR9)N(R)2, N(OR)C(═CHR9)N(R)2, C(═NR9)R, C(O)N(R)OR, and C(═NR9)N(R)2, and each n is independently selected from 1, 2, 3, 4, and 5; and when Q is a 5- to 14-membered heterocycle and (i) R4 is (CH2)nQ in which n is 1 or 2, or (ii) R4 is (CH2)nCHQR in which n is 1, or (iii) R4 is CHQR, and CQ(R)2, then Q is either a 5- to 14-membered heteroaryl or 8- to 14-membered heterocycloalkyl;

    • each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • M and M′ are independently selected from C(O)O, OC(O), C(O)N(R′), N(R′)C(O), C(O), C(S), C(S)S, SC(S), CH(OH), P(0)(OR′)O, S(O)2, S, an aryl group, and a heteroaryl group;

    • R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • R8 is selected from the group consisting of C3-6 carbocycle and heterocycle;

    • R9 is selected from the group consisting of H, CN, NO2, C1-6 alkyl, —OR, —S(O)2R, —S(O)2N(R)2, C2-6 alkenyl, C3-6 carbocycle and heterocycle;

    • each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, R*YR″, YR″, and H;

    • each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;

    • each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;

    • each Y is independently a C3-6 carbocycle;

    • each X is independently selected from the group consisting of F, Cl, Br, and I; and

    • m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,

    • or salts or isomers thereof.

    • 26. The vaccine of paragraph 22, wherein a subset of compounds of Formula (I) includes those in which

    • R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, R*YR″, YR″, and R″M′R′;

    • R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, C2-14 alkenyl, R*YR″, YR″, and R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;

    • R4 is selected from the group consisting of a C3-6 carbocycle, (CH2)nQ, (CH2)nCHQR, CHQR, CQ(R)2, and unsubstituted C1-6 alkyl, where Q is selected from a C3-6 carbocycle, a 5- to 14-membered heteroaryl having one or more heteroatoms selected from N, O, and S, —OR, —O(CH2)nN(R)2, C(O)OR, —OC(O)R, CX3, CX2H, CXH2, CN, C(O)N(R)2, N(R)C(O)R, N(R)S(O)2R, N(R)C(O)N(R)2, N(R)C(S)N(R)2, CRN(R)2C(O)OR, N(R)R8, O(CH2)nOR, N(R)C(═NR9)N(R)2, N(R)C(═CHR9)N(R)2, OC(O)N(R)2, N(R)C(O)OR, N(OR)C(O)R, N(OR)S(O)2R, N(OR)C(O)OR, N(OR)C(O)N(R)2, N(OR)C(S)N(R)2, N(OR)C(═NR9)N(R)2, N(OR)C(═CHR9)N(R)2, C(═NR9)R, C(O)N(R)OR, and C(═NR9)N(R)2, and each n is independently selected from 1, 2, 3, 4, and 5; each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • M and M′ are independently selected from C(O)O, OC(O), C(O)N(R′), N(R′)C(O), C(O), C(S), C(S)S, SC(S), CH(OH), P(0)(OR′)O, S(O)2, SS, an aryl group, and a heteroaryl group;

    • R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • R8 is selected from the group consisting of C3-6 carbocycle and heterocycle;

    • R9 is selected from the group consisting of H, CN, NO2, C1-6 alkyl, —OR, —S(O)2R, —S(O)2N(R)2, C2-6 alkenyl, C3-6 carbocycle and heterocycle;

    • each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, R*YR″, YR″, and H;

    • each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;

    • each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;

    • each Y is independently a C3-6 carbocycle;

    • each X is independently selected from the group consisting of F, Cl, Br, and I; and

    • m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,

    • or salts or isomers thereof.

    • 27. The vaccine of paragraph 22, wherein a subset of compounds of Formula (I) includes those in which

    • R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, R*YR″, YR″, and R″M′R′;

    • R2 and R3 are independently selected from the group consisting of H, C2-14 alkyl, C2-14 alkenyl, R*YR″, YR″, and R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;

    • R4 is (CH2)nQ or (CH2)nCHQR, where Q is N(R)2, and n is selected from 3, 4, and 5; each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • M and M′ are independently selected from C(O)O, OC(O), C(O)N(R′), N(R′)C(O), C(O), C(S), C(S)S, SC(S), CH(OH), P(0)(OR′)O, S(O)2, SS, an aryl group, and a heteroaryl group;

    • R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, R*YR″, YR″, and H;

    • each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;

    • each R* is independently selected from the group consisting of C1-12 alkyl and C1-12 alkenyl;

    • each Y is independently a C3-6 carbocycle;

    • each X is independently selected from the group consisting of F, Cl, Br, and I; and

    • m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,

    • or salts or isomers thereof.

    • 28. The vaccine of paragraph 22, wherein a subset of compounds of Formula (I) includes those in which

    • R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, R*YR″, YR″, and R″M′R′;

    • R2 and R3 are independently selected from the group consisting of C1-14 alkyl, C2-14 alkenyl, R*YR″, YR″, and R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;

    • R4 is selected from the group consisting of (CH2)nQ, (CH2)nCHQR, CHQR, and CQ(R)2, where Q is N(R)2, and n is selected from 1, 2, 3, 4, and 5;

    • each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • M and M′ are independently selected from C(O)O, OC(O), C(O)N(R′), N(R′)C(O), C(O), C(S), C(S)S, SC(S), CH(OH), P(O)(OR′)O, S(O)2, SS, an aryl group, and a heteroaryl group;

    • R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;

    • each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, R*YR″, YR″, and H;

    • each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;

    • each R* is independently selected from the group consisting of C1-12 alkyl and C1-12 alkenyl;

    • each Y is independently a C3-6 carbocycle;

    • each X is independently selected from the group consisting of F, Cl, Br, and I; and

    • m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,

    • or salts or isomers thereof.

    • 29. The vaccine of paragraph 22, wherein a subset of compounds of Formula (I) includes those of Formula (IA):







embedded image




    • or a salt or isomer thereof, wherein 1 is selected from 1, 2, 3, 4, and 5; m is selected from 5, 6, 7, 8, and 9; M1 is a bond or M′; R4 is unsubstituted C1-3 alkyl, or (CH2)nQ, in which Q is OH, NHC(S)N(R)2, NHC(O)N(R)2, N(R)C(O)R, N(R)S(O)2R, N(R)R8, NHC(═NR9)N(R)2, NHC(═CHR9)N(R)2, —OC(O)N(R)2, N(R)C(O)OR, heteroaryl or heterocycloalkyl; M and M′ are independently selected from C(O)O, OC(O), C(O)N(R′), P(O)(OR′)O, SS, an aryl group, and a heteroaryl group; and R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, and C2-14 alkenyl.





This invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments and of being practiced or of being carried out in various ways. Also, the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having,” “containing,” “involving,” and variations thereof herein, is meant to encompass the items listed thereafter and equivalents thereof as well as additional items.


Examples
Example 1: Manufacture of Polynucleotides

According to the present disclosure, the manufacture of polynucleotides and/or parts or regions thereof may be accomplished utilizing the methods taught in International Publication WO2014/152027, entitled “Manufacturing Methods for Production of RNA Transcripts,” the contents of which is incorporated herein by reference in its entirety.


Purification methods may include those taught in International Publication WO2014/152030 and International Publication WO2014/152031, each of which is incorporated herein by reference in its entirety.


Detection and characterization methods of the polynucleotides may be performed as taught in International Publication WO2014/144039, which is incorporated herein by reference in its entirety.


Characterization of the polynucleotides of the disclosure may be accomplished using polynucleotide mapping, reverse transcriptase sequencing, charge distribution analysis, detection of RNA impurities, or any combination of two or more of the foregoing. “Characterizing” comprises determining the RNA transcript sequence, determining the purity of the RNA transcript, or determining the charge heterogeneity of the RNA transcript, for example. Such methods are taught in, for example, International Publication WO2014/144711 and International Publication WO2014/144767, the content of each of which is incorporated herein by reference in its entirety.


Example 2: Chimeric Polynucleotide Synthesis

According to the present disclosure, two regions or parts of a chimeric polynucleotide may be joined or ligated using triphosphate chemistry. A first region or part of 100 nucleotides or less is chemically synthesized with a 5′ monophosphate and terminal 3′desOH or blocked OH, for example. If the region is longer than 80 nucleotides, it may be synthesized as two strands for ligation.


If the first region or part is synthesized as a non-positionally modified region or part using in vitro transcription (IVT), conversion the 5′ monophosphate with subsequent capping of the 3′ terminus may follow.


Monophosphate protecting groups may be selected from any of those known in the art.


The second region or part of the chimeric polynucleotide may be synthesized using either chemical synthesis or IVT methods. IVT methods may include an RNA polymerase that can utilize a primer with a modified cap. Alternatively, a cap of up to 130 nucleotides may be chemically synthesized and coupled to the IVT region or part.


For ligation methods, ligation with DNA T4 ligase, followed by treatment with DNase should readily avoid concatenation.


The entire chimeric polynucleotide need not be manufactured with a phosphate-sugar backbone. If one of the regions or parts encodes a polypeptide, then such region or part may comprise a phosphate-sugar backbone.


Ligation is then performed using any known click chemistry, orthoclick chemistry, solulink, or other bioconjugate chemistries known to those in the art.


Synthetic Route


The chimeric polynucleotide may be made using a series of starting segments. Such segments include:

    • (a) a capped and protected 5′ segment comprising a normal 3′OH (SEG. 1)
    • (b) a 5′ triphosphate segment, which may include the coding region of a polypeptide and a normal 3′OH (SEG. 2)
    • (c) a 5′ monophosphate segment for the 3′ end of the chimeric polynucleotide (e.g., the tail) comprising cordycepin or no 3′OH (SEG. 3)


After synthesis (chemical or IVT), segment 3 (SEG. 3) may be treated with cordycepin and then with pyrophosphatase to create the 5′ monophosphate.


Segment 2 (SEG. 2) may then be ligated to SEG. 3 using RNA ligase. The ligated polynucleotide is then purified and treated with pyrophosphatase to cleave the diphosphate. The treated SEG.2-SEG. 3 construct may then be purified and SEG. 1 is ligated to the 5′ terminus. A further purification step of the chimeric polynucleotide may be performed.


Where the chimeric polynucleotide encodes a polypeptide, the ligated or joined segments may be represented as: 5′UTR (SEG. 1), open reading frame or ORF (SEG. 2) and 3′UTR+PolyA (SEG. 3).


The yields of each step may be as much as 90-95%.


Example 3: PCR for cDNA Production

PCR procedures for the preparation of cDNA may be performed using 2×KAPA HIFI™ HotStart ReadyMix by Kapa Biosystems (Woburn, MA). This system includes 2×KAPA ReadyMix 12.5 μl; Forward Primer (10 μM) 0.75 μl; Reverse Primer (10 μM) 0.75 μl; Template cDNA 100 ng; and dH20 diluted to 25.0 μl. The reaction conditions may be at 95° C. for 5 min. The reaction may be performed for 25 cycles of 98° C. for 20 sec, then 58° C. for 15 sec, then 72° C. for 45 sec, then 72° C. for 5 min, then 4° C. to termination.


The reaction may be cleaned up using Invitrogen's PURELINK™ PCR Micro Kit (Carlsbad, CA) per manufacturer's instructions (up to 5 μg). Larger reactions may require a cleanup using a product with a larger capacity. Following the cleanup, the cDNA may be quantified using the NANODROP™ and analyzed by agarose gel electrophoresis to confirm that the cDNA is the expected size. The cDNA may then be submitted for sequencing analysis before proceeding to the in vitro transcription reaction.


Example 4: In Vitro Transcription (IVT)

The in vitro transcription reaction generates RNA polynucleotides. Such polynucleotides may comprise a region or part of the polynucleotides of the disclosure, including chemically modified RNA (e.g., mRNA) polynucleotides. The chemically modified RNA polynucleotides can be uniformly modified polynucleotides. The in vitro transcription reaction utilizes a custom mix of nucleotide triphosphates (NTPs). The NTPs may comprise chemically modified NTPs, or a mix of natural and chemically modified NTPs, or natural NTPs.


A typical in vitro transcription reaction includes the following:

















1)
Template cDNA
1.0
μg


2)
10× transcription buffer
2.0
μl



(400 mM Tris-HCl pH 8.0, 190 mM





MgCl2, 50 mM DTT, 10 mM Spermi-





dine)




3)
Custom NTPs (25 mM each)
0.2
μl


4)
RNase Inhibitor
20
U


5)
T7 RNA polymerase
3000
U









6)
dH20
up to 20.0 μl. and










7)
Incubation at 37° C. for 3 hr-5 hrs.











The crude IVT mix may be stored at 4° C. overnight for cleanup the next day. 1 U of RNase-free DNase may then be used to digest the original template. After 15 minutes of incubation at 37° C., the mRNA may be purified using Ambion's MEGACLEAR™ Kit (Austin, TX) following the manufacturer's instructions. This kit can purify up to 500 μg of RNA. Following the cleanup, the RNA polynucleotide may be quantified using the NANODROP™ and analyzed by agarose gel electrophoresis to confirm the RNA polynucleotide is the proper size and that no degradation of the RNA has occurred.


Example 5: Enzymatic Capping

Capping of a RNA polynucleotide is performed as follows where the mixture includes: IVT RNA 60 μg-180 μg and dH20 up to 72 μl. The mixture is incubated at 65° C. for 5 minutes to denature RNA, and then is transferred immediately to ice.


The protocol then involves the mixing of 10× Capping Buffer (0.5 M Tris-HCl (pH 8.0), 60 mM KCl, 12.5 mM MgCl2) (10.0 μl); 20 mM GTP (5.0 μl); 20 mM S-Adenosyl Methionine (2.5 μl); RNase Inhibitor (100 U); 2′-O-Methyltransferase (400U); Vaccinia capping enzyme (Guanylyl transferase) (40 U); dH20 (Up to 28 μl); and incubation at 37° C. for 30 minutes for 60 μg RNA or up to 2 hours for 180 μg of RNA.


The RNA polynucleotide may then be purified using Ambion's MEGACLEAR™ Kit (Austin, TX) following the manufacturer's instructions. Following the cleanup, the RNA may be quantified using the NANODROP™ (ThermoFisher, Waltham, MA) and analyzed by agarose gel electrophoresis to confirm the RNA polynucleotide is the proper size and that no degradation of the RNA has occurred. The RNA polynucleotide product may also be sequenced by running a reverse-transcription-PCR to generate the cDNA for sequencing.


Example 6: PolyA Tailing Reaction

Without a poly-T in the cDNA, a poly-A tailing reaction must be performed before cleaning the final product. This is done by mixing capped IVT RNA (100 μl); RNase Inhibitor (20 U); 10× Tailing Buffer (0.5 M Tris-HCl (pH 8.0), 2.5 M NaCl, 100 mM MgCl2) (12.0 μl); 20 mM ATP (6.0 μl); Poly-A Polymerase (20 U); dH20 up to 123.5 μl and incubation at 37° C. for 30 min. If the poly-A tail is already in the transcript, then the tailing reaction may be skipped and proceed directly to cleanup with Ambion's MEGACLEAR™ kit (Austin, TX) (up to 500 μg). Poly-A Polymerase may be a recombinant enzyme expressed in yeast.


It should be understood that the processivity or integrity of the polyA tailing reaction may not always result in an exact size polyA tail. Hence, polyA tails of approximately between 40-200 nucleotides, e.g., about 40, 50, 60, 70, 80, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 150-165, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164 or 165 are within the scope of the present disclosure.


Example 7: Natural 5′ Caps and 5′ Cap Analogues

5′-capping of polynucleotides may be completed concomitantly during the in vitro-transcription reaction using the following chemical RNA cap analogs to generate the 5′-guanosine cap structure according to manufacturer protocols: 3′-O-Me-m7G(5′)ppp(5′) G [the ARCA cap]; G(5′)ppp(5′)A; G(5′)ppp(5′)G; m7G(5′)ppp(5′)A; m7G(5′)ppp(5′)G (New England BioLabs, Ipswich, MA). 5′-capping of modified RNA may be completed post-transcriptionally using a Vaccinia Virus Capping Enzyme to generate the “Cap 0” structure: m7G(5′)ppp(5′)G (New England BioLabs, Ipswich, MA). Cap 1 structure may be generated using both Vaccinia Virus Capping Enzyme and a 2′-O methyl-transferase to generate: m7G(5′)ppp(5′)G-2′-O-methyl. Cap 2 structure may be generated from the Cap 1 structure followed by the 2′-O-methylation of the 5′-antepenultimate nucleotide using a 2′-O methyl-transferase. Cap 3 structure may be generated from the Cap 2 structure followed by the 2′-O-methylation of the 5′-preantepenultimate nucleotide using a 2′-O methyl-transferase. Enzymes are preferably derived from a recombinant source.


When transfected into mammalian cells, the modified mRNAs have a stability of between 12-18 hours or more than 18 hours, e.g., 24, 36, 48, 60, 72 or greater than 72 hours.


Example 8: Capping Assays
Protein Expression Assay

Polynucleotides (e.g., mRNA) encoding a polypeptide, containing any of the caps taught herein, can be transfected into cells at equal concentrations. The amount of protein secreted into the culture medium can be assayed by ELISA at 6, 12, 24 and/or 36 hours post-transfection. Synthetic polynucleotides that secrete higher levels of protein into the medium correspond to a synthetic polynucleotide with a higher translationally-competent cap structure.


Purity Analysis Synthesis

RNA (e.g., mRNA) polynucleotides encoding a polypeptide, containing any of the caps taught herein can be compared for purity using denaturing Agarose-Urea gel electrophoresis or HPLC analysis. RNA polynucleotides with a single, consolidated band by electrophoresis correspond to the higher purity product compared to polynucleotides with multiple bands or streaking bands. Chemically modified RNA polynucleotides with a single HPLC peak also correspond to a higher purity product. The capping reaction with a higher efficiency provides a more pure polynucleotide population.


Cytokine Analysis

RNA (e.g., mRNA) polynucleotides encoding a polypeptide, containing any of the caps taught herein can be transfected into cells at multiple concentrations. The amount of pro-inflammatory cytokines, such as TNF-alpha and IFN-beta, secreted into the culture medium can be assayed by ELISA at 6, 12, 24 and/or 36 hours post-transfection. RNA polynucleotides resulting in the secretion of higher levels of pro-inflammatory cytokines into the medium correspond to a polynucleotides containing an immune-activating cap structure.


Capping Reaction Efficiency

RNA (e.g., mRNA) polynucleotides encoding a polypeptide, containing any of the caps taught herein can be analyzed for capping reaction efficiency by LC-MS after nuclease treatment. Nuclease treatment of capped polynucleotides yield a mixture of free nucleotides and the capped 5′-5-triphosphate cap structure detectable by LC-MS. The amount of capped product on the LC-MS spectra can be expressed as a percent of total polynucleotide from the reaction and correspond to capping reaction efficiency. The cap structure with a higher capping reaction efficiency has a higher amount of capped product by LC-MS.


Example 9: Agarose Gel Electrophoresis of Modified RNA or RT PCR Products

Individual RNA polynucleotides (200-400 ng in a 20 μl volume) or reverse transcribed PCR products (200-400 ng) may be loaded into a well on a non-denaturing 1.2% Agarose E-Gel (Invitrogen, Carlsbad, CA) and run for 12-15 minutes, according to the manufacturer protocol.


Example 10: NANODROP™ Modified RNA Quantification and UV Spectral Data

Chemically modified RNA polynucleotides in TE buffer (1 μl) are used for NANODROP™ UV absorbance readings to quantitate the yield of each polynucleotide from an chemical synthesis or in vitro transcription reaction.


Example 11: Formulation of Modified mRNA Using Lipidoids

RNA (e.g., mRNA) polynucleotides may be formulated for in vitro experiments by mixing the polynucleotides with the lipidoid at a set ratio prior to addition to cells. In vivo formulation may require the addition of extra ingredients to facilitate circulation throughout the body. To test the ability of these lipidoids to form particles suitable for in vivo work, a standard formulation process used for siRNA-lipidoid formulations may be used as a starting point. After formation of the particle, polynucleotide is added and allowed to integrate with the complex. The encapsulation efficiency is determined using a standard dye exclusion assays.


Example 12: Mouse Immunogenicity Studies
Comparison of HA Stem Antigens

In this example, assays were carried out to evaluate the immune response to influenza virus vaccine antigens delivered using an mRNA/LNP platform in comparison to protein antigens. The instant study was designed to test the immunogenicity in mice of candidate influenza virus vaccines comprising an mRNA polynucleotide encoding HA stem protein obtained from different strains of influenza virus. Animals tested were 6-8 week old female BALB/c mice obtained from Charles River Laboratories. Test vaccines included the following mRNAs formulated in MC3 LNP: stem of H1/Puerto Rico/8/1934 (based on Mallajosyula V et al. PNAS 2014 Jun. 24; 111(25):E2514-23), stem of H1/New Caledonia/20/1999 (based on Mallajosyula V et al. PNAS 2014 Jun. 24; 111(25):E2514-23), stem of H1/California/04/2009 (based on Mallajosyula V et al. PNAS 2014 Jun. 24; 111(25):E2514-23), stem of H5/Vietnam/1194/2004 (based on Mallajosyula V et al. PNAS 2014 Jun. 24; 111(25):E2514-23), stem of H10/Jiangxi-Donghu/346/2013, and full-length H10/Jiangxi-Donghu/346/2013.


Protein vaccines tested in this study included the pH1HA10-Foldon protein, as described in Mallajosyula et al. Proc Natl Acad Sci USA. 2014; 111(25):E2514-23. Additional controls included MC3 (control for effects of LNP) and PR8 influenza virus.


Mice were immunized intramuscularly with a total volume of 100 μL of each test vaccine, which was administered in a 50 μL immunization to each quadricep, except for administration of the PR8 influenza virus control which was delivered intranasally in a volume of 20 μL while the animals were sedated with a mixture of Ketamine and Xylazine. The group numbers for each test vaccine along with the vaccine dose are outlined in the table below:









TABLE 1







RNA Test Vaccines










Group #
Antigen
dose
formulation





1
H10/Jiangxi-
10 μg
MC3



Donghu/346/2013 full-length





RNA




2
H10N8 A/JX346/2013 stem
10 μg
MC3



RNA




3
H1N1 A/Puerto Rico/8/1934
10 μg
MC3



stem RNA




4
H1N1 A/New
10 μg
MC3



Caledonia/20/99 stem RNA




5
H1N1 A/Califomia/04/2009
10 μg
MC3



stem RNA




6
H5N1 A/Vietnam/1203/2004
10 μg
MC3



stem RNA




7
pH1HA10-Foldon protein
20 μg
CpG 7909


8
MC3
 0 μg
MC3


9
0.1 LD90 PR8 virus
0.1 LD90
None










Mice were immunized with two doses of the various influenza virus RNA vaccine formulations at weeks 0 and 3, and serum was collected two weeks after immunization with the second dose.


To test the sera for the presence of antibodies capable of binding to hemagglutinin (HA) from a wide variety of influenza strains, ELISA plates were coated with 100 ng of the following recombinant HAs obtained from Sino Biological Inc.: Influenza A H1N1 (A/New Caledonia/20/99), cat #11683-V08H; Influenza A H3N2 (A/Aichi/2/1968), cat #11707-V08H; Influenza A H1N1 (A/California/04/2009) cat #11055-V08H; Influenza A H1N1 (A/Puerto Rico/8/34) cat #11684-V08H; Influenza A H3N2 (A/Brisbane/10/2007), cat #11056-V08H; Influenza A H2N2 (A/Japan/305/1957) cat #11088-V08H; Influenza A H7N9 (A/Anhui/1/2013) cat #40103-V08H; Influenza H5N1 (A/Vietnam/1194/2004) cat #11062-V08H1; Influenza H9N2 (A/Hong Kong/1073/99) cat #11229-V08H and Influenza A H10N8 (A/Jiangxi-Donghu/346/2013) cat #40359-V08B. After coating, the plates were washed, blocked with Phosphate Buffered Saline with 0.05% Tween-20 (PBST)+3% milk, and 100 μL of control antibodies or sera from immunized mice (diluted in PBST+3% milk) were added to the top well of each plate and serially diluted. Plates were sealed and incubated at room temperature for 2 hours. Plates were washed, and goat anti-mouse IgG (H+L)-HRP conjugate (Novex, diluted 1:2000 in PBST/3% milk) was added to each well containing mouse sera. Plates were incubated at room temperature for 1 hr, washed, and incubated with TMB substrate (Thermo Scientific). The color was allowed to develop for 10 minutes and then quenched with 100 μL of 2N sulfuric acid. The plates were read at 450 nM on a microplate reader. Endpoint titers (2.5-fold above background) were calculated.


In FIG. 1, the vaccines tested are shown on the y-axis and the endpoint titer to HA from each of the different strains of influenza are plotted. HAs from group 1 (H1, H2, H5, H9) strains of influenza are indicated by filled circles while HAs from group 2 (H3, H7, H10) strains of influenza are indicated by open circles. FIG. 1 illustrates that mRNA based vaccines encoding HA-based antigens that are encapsulated in the MC3 lipid nanoparticle induced high antibody binding titers to HA. FIG. 1 also illustrates that mRNA vaccines designed to express a portion of the stem domain from different H1N1 or H5N1 strains of influenza elicited high antibody titers that were capable of binding all strains of group 1 HA tested as well as several group 2 strains. FIG. 1 also illustrates that mRNA vaccines designed to express a portion of the H1N1 A/California/04/2009 stem domain induced higher titers than a protein vaccine of the same stem domain.


In another mouse immunogenicity study, the immune response to additional influenza virus vaccine antigens delivered using an mRNA/LNP platform was evaluated. The purpose of this study was to evaluate the ability of a second set of mRNA vaccine antigens to elicit cross-protective immune responses in the mouse and to assess the potential for mRNA vaccines encoding influenza HA antigens to be co-dosed. Animals tested were 6-8 week old female BALB/c mice obtained from Charles River Laboratories. Test vaccines included the following mRNAs formulated in MC3 LNP: H1HA6 (based on Bommakanti G et al. J Virol. 2012 Dec; 86(24):13434-44); H3HA6 (based on Bommakanti G et al. PNAS 2010 Aug. 3; 107(31):13701-6); H1HA10-Foldon_delta Ngly; eH1HA (ectodomain of HA from H1N1 A/Puerto Rico/8/34); eH1HA_native signal seq (eH1HA with its native signal sequence); H3N2 A/Wisconsin/67/2005 stem; H3N2 A/Hong Kong/1/1968 stem (based on Mallajosyula V et al. Front Immunol. 2015 Jun. 26; 6:329); H7N9 A/Anhui/1/2013 stem; H1N1 A/California/04/2009 stem RNA (based on Mallajosyula V et al. PNAS 2014 Jun. 24; 111(25):E2514-23); and H1N1 A/Puerto Rico/8/1934 stem RNA (based on Mallajosyula V et al. PNAS 2014 Jun. 24; 111(25):E2514-23).


Controls included: MC3 (control for effects of LNP); Naïve (unvaccinated animals); and vaccination with H1N1 A/PR/8/34 and H3N2 A/HK/1/68 influenza viruses (positive controls).


Mice were immunized intramuscularly with a total volume of 100 μL of each test vaccine, which was administered in a 50 μL immunization to each quadricep, except for administration of the H1N1 A/PR/8/34 and H3N2 A/HK/1/68 virus influenza virus controls which were delivered intranasally in a volume of 20 μL while the animals were sedated with a mixture of Ketamine and Xylazine. The group numbers for each test vaccine along with the vaccine dose are outlined in the table below:









TABLE 2







Test Vaccines














For-





Antigen
mula-
Volume,


Group #
Antigen
dose
tion
Route














1
H1HA6 RNA
10 μg
MC3
100 μl, i.m.


2
H3HA6 RNA
10 μg
MC3
100 μl, i.m.


3
H1HA10-Foldon_delta Ngly
10 μg
MC3
100 μl, i.m.


4
eH1HA
10 μg
MC3
100 μl, i.m.


5
eH1HA_native signal seq
10 μg
MC3
100 μl, i.m.


6
H3N2 A/Wisconsin/67/2005
10 μg
MC3
100 μl, i.m.



stem RNA





7
H3N2 A/Hong Kong/1/1968
10 μg
MC3
100 μl, i.m.



stem RNA





8
H7N9 A/Anhui/1/2013 stem
10 μg
MC3
100 μl, i.m.



RNA





9
H1N1 A/Puerto Rico/8/1934
10 μg
MC3
100 μl, i.m.



stem RNA AND H3N2






A/Wisconsin/67/2005 stem






RNA (RNAs mixed prior to






formulation)





10
H1N1 A/Puerto Rico/8/1934
10 μg
MC3
100 μl, i.m.



stem RNA AND H3N2






A/Wisconsin/67/2005 stem






RNA (RNAs formulated and






then mixed





11
H1N1 A/California/04/2009
10 μg
MC3
100 μl, i.m.



stem RNA





12
H1N1 A/Puerto Rico/8/1934
10 μg
MC3
100 μl, i.m.



stem RNA





13
MC3
 0 μg
MC3
100 μl, i.m.


14
Naïve
 0 μg
None
None


15
H3N2 A/HK/1/68 virus
0.1 LD90
None
 20 μl, i.n.


16
H1N1 A/PR/8/34 virus
0.1 LD90
None
 20 μl, i.n.









Animals were immunized on the study start day and then again three weeks after the initial immunization. Sera were collected from the animals two weeks after the second dose. To test the sera for the presence of antibodies capable of binding to hemagglutinin (HA) from a wide variety of influenza strains, ELISA plates were coated with 100 ng of the following recombinant HAs obtained from Sino Biological Inc.: Influenza A H1N1 (A/New Caledonia/20/99), cat #11683-VO8H; Influenza A H3N2 (A/Aichi/2/1968), cat #11707-V08H; Influenza A H1N1 (A/California/04/2009) cat #11055-VO8H; Influenza A H1N1 (A/Puerto Rico/8/34) cat #11684-VO8H; Influenza A H3N2 (A/Brisbane/10/2007), cat #11056-VO8H; Influenza A H2N2 (A/Japan/305/1957) cat #11088-VO8H; Influenza A H7N9 (A/Anhui/l/2013) cat #40103-VO8H and Influenza A H3N2 (A/Moscow/10/99) cat #40154-V08. The ELISA assay was performed and endpoint titers were calculated as described above. FIGS. 2 and 3 show the endpoint anti-HA antibody titers following the second immunization with the test vaccines. The vaccines tested are shown on the x-axis and the binding to HA from each of the different strains of influenza is plotted. All mRNA vaccines encoding HA stem were immunogenic and elicited a robust antibody response recognizing HA from a diverse set of influenza A virus strains. The H1HA6, eH1HA, and eH1HA_native-signal-sequence mRNAs elicited the highest overall binding titers across the panel of group 1 HAs, while the H3HA6 RNA elicited the highest overall binding titers across group 2 Has (FIG. 2). Immunogenicity of combinations of stem mRNA vaccines was also tested. In this study, individual mRNAs were mixed prior to formulation with LNP (Group 9, co-form) or individual mRNAs were formulated with LNP prior to mixing (Group 10, mix-form). As shown in FIG. 3, combining H1 and H3 stem-based mRNAs did not result in interference in the immune response to either antigen, regardless of the method of formulation.


Example 13: Mouse Efficacy Studies

Influenza A challenge #1


This study was designed to test the immunogenicity and efficacy in mice of candidate influenza virus vaccines. Animals tested were 6-8 week old female BALB/c mice obtained from Charles River Laboratories. Test vaccines included the following mRNAs formulated in MC3 LNP: NIHGen6HASS-foldon mRNA (based on Yassine et al. Nat. Med. 2015 September; 21(9):1065-70), an mRNA encoding the nucleoprotein NP from an H3N2 strain, or one of several combinations of NIHGen6HASS-foldon and NP mRNAs. Several methods of vaccine antigen co-delivery were tested including: mixing individual mRNAs prior to formulation with LNP (co-form), formulation of individual mRNAs prior to mixing (mix ind LNPs), and formulating mRNAs individually and injecting distal sites (opposite legs) (ind LNPs remote). Control animals were vaccinated with an RNA encoding the ectodomain of the HA from H1N1 A/Puerto Rico/8/1934 (eH1HA, positive control) or empty MC3 LNP (to control for effects of the LNP) or were not vaccinated (naïve).


At week 0 and week 3, animals were immunized intramuscularly (IM) with a total volume of 100 μL of each test vaccine, which was administered in a 50 μL immunization to each quadricep. Candidate influenza virus vaccines evaluated in this study were described above and are outlined in the table below. Sera were collected from all animals two weeks after the second dose. At week 6, spleens were harvested from a subset of the animals (n=4). The remaining animals (n=6) were challenged intranasally while sedated with a mixture of Ketamine and Xylazine with a lethal dose of mouse-adapted influenza virus strain H1N1 A/Puerto Rico/8/1934. Mortality was recorded and individual mouse weight was assessed daily for 20 days post-infection.









TABLE 3







Test Vaccines











Group


Formu-
Volume,


#
Antigen
Antigen dose
lation
Route














1
NIHGen6HASS-foldon
10 μg 
MC3
100 μl, i.m.



RNA





2
NIHGen6HASS-foldon
5 μg
MC3
100 μl, i.m.



RNA





3
NIHGen6HASS-foldon
2 μg
MC3
100 μl, i.m.



RNA





4
NP RNA
5 μg
MC3
100 μl, i.m.


5
NIHGen6HASS-foldon
5 μg of each
MC3
100 μl, i.m.



RNA + NP RNA
RNA mixed,






then formulated




6
NIHGen6HASS-foldon
5 μg of each
MC3
100 μl, i.m.



RNA + NP RNA
RNA formulated,






then mixed




7
NIHGen6HASS-foldon
5 μg of each
MC3
100 μl, i.m.



RNA + NP RNA
RNA formulated






and injected into






separate legs




8
NIHGen6HASS-foldon
5 μg of NP +
MC3
100 μl, i.m.



RNA + NP RNA
2 μg of






NIHGen6HASS-foldon






RNA mixed, then






formulated




9
eH1HA RNA
10 μg 
MC3
100 μl, i.m.


10
MC3
0 μg
MC3
100 μl, i.m.


11
Naïve
0 μg
None
None









To test the sera for the presence of antibodies capable of binding to hemagglutinin (HA) from a wide variety of influenza strains or nucleoprotein (NP), ELISA plates were coated with 100 ng of the following recombinant proteins obtained from Sino Biological Inc.: Influenza A H1N1 (A/New Caledonia/20/99) HA, cat #11683-VO8H; Influenza A H3N2 (A/Aichi/2/1968) HA, cat #11707-VO8H; Influenza A H1N1 (A/California/04/2009) HA, cat #11055-VO8H; Influenza A H1N1 (A/Puerto Rico/8/34) HA, cat #11684-VO8H; Influenza A H1N1 (A/Brisbane/59/2007) HA, cat #11052-VO8H; Influenza A H2N2 (A/Japan/305/1957) HA, cat #11088-VO8H; Influenza A H7N9 (A/Anhui/l/2013) HA, cat #40103-VO8H, Influenza A H3N2 (A/Moscow/10/99) HA, cat #40154-V08 and Influenza A H3N2 (A/Aichi/2/1968) Nucleoprotein cat #40207-V08B. The ELISA assay was performed and endpoint titers were calculated as described above. FIG. 4 depicts the endpoint titers of the pooled serum from animals vaccinated with the test vaccines. The vaccines tested are shown on the x-axis of FIG. 4A and the binding to HA from each of the different strains of influenza is plotted. The NIHGen6HASS-foldon mRNA vaccine elicited high titers of antibodies that bound all H1, H2 and H7 HAs tested. Combining the NIHGen6HASS-foldon mRNA with one that encodes NP did not negatively affect the observed anti-HA response, regardless of the method of mRNA co-formulation or co-delivery. In serum collected from identical groups from a separate study, a robust antibody response to NP protein was also detected in serum from animals vaccinated with NP mRNA containing vaccines, either NP alone or co-formulated with NIHGen6HASS-foldon mRNA(FIG. 4B).


To probe the functional antibody response, the ability of serum to neutralize a panel of HA-pseudotyped viruses was assessed (FIG. 5). Briefly, 293 cells were co-transfected with a replication-defective retroviral vector containing a firefly luciferase gene, an expression vector encoding a human airway serine protease, and expression vectors encoding influenza hemagglutinin (HA) and neuraminidase (NA) proteins. The resultant pseudoviruses were harvested from the culture supernatant, filtered, and titered. Serial dilutions of serum were incubated in 96 well plates at 37° C. for one hour with pseudovirus stocks (30,000-300,000 relative light units per well) before 293 cells were added to each well. The cultures were incubated at 37° C. for 72 hours, luciferase substrate and cell lysing reagents were added, and relative light units (RLU) were measured on a luminometer. Neutralization titers are expressed as the reciprocal of the serum dilution that inhibited 50% of pseudovirus infection (IC50).


For each sample tested (listed along the x-axis), each bar represents the IC50 for neutralization of a different virus pseudotype. While the serum from naïve or NP RNA vaccinated mice was unable to inhibit pseudovirus infection, the serum from mice vaccinated with 10 μg or 5 μg of NIHGen6HASS-foldon mRNA or with a combination of NIHGen6HASS-foldon and NP mRNAs neutralized, to a similar extent, all H1 and H5 virus pseudotypes tested.


The ability of NIHGen6HASS-foldon antisera to mediate antibody-dependent cell cytotoxicity (ADCC) surrogate activity in vitro was also assessed. Briefly, serially titrated mouse serum samples were incubated with A549 cells stably expressing HA from HIN1 A/Puerto Rico/8/1934 on the cell surface. Subsequently, ADCC Bioassay Effector cells (Promega, mouse FcgRIV NFAT-Luc effector cells) were added to the serum/target cell mixture. Approximately 6 hours later, Bio-glo reagent (Promega) was added to sample wells and luminescence was measured. Data was plotted as fold induction (sample luminescence/background luminescence) versus serum concentration (FIG. 6). When incubated with the appropriate target cells, serum from NIHGen6HASS-foldon mRNA vaccinated mice was able to stimulate the surrogate ADCC effector cell line, suggesting that the vaccine may induce antibodies capable of mediating in vivo ADCC activity.


Three weeks after the administration of the second vaccine dose, spleens were harvested from a subset of animals in each group and splenocytes from animals in the same group were pooled. Splenic lymphocytes were stimulated with a pool of HA or NP peptides, and IFN-γ, IL-2 or TNF-α production was measured by intracellular staining and flow cytometry. FIG. 7 is a representation of responses following stimulation with a pool of NP peptides, and FIG. 8 is a representation of responses following stimulation with a pool of H1 HA peptides. Following vaccination with NP mRNA, either in the presence or absence of NIHGen6HASS-foldon mRNA, antigen-specific CD4 and CD8 T cells were found in the spleen. Following vaccination with NIHGen6HASS-foldon RNA or delivery of NIHGen6HASS-foldon and NP RNAs to distal injections sites (dist. site), only HA-specific CD4 cells were observed. However, when NIHGen6HASS-foldon and NP RNAs were co-administered to the same injection site (co-form, mix), an HA-specific CD8 T cell response was detected.


Following lethal challenge with mouse-adapted HIN1 A/Puerto Rico/8/1934, all naïve animals succumbed to infection by day 12 post-infection (FIG. 9). In contrast, all animals vaccinated with NIHGen6HASS-foldon mRNA, NP mRNA, any combination of NIHGen6HASS-foldon and NP mRNAs, or eH1HA mRNA survived the challenge. As seen in FIG. 9, although there was no mortality, mice that were vaccinated with an H3N2 NP mRNA and challenged with HIN1 virus lost a significant amount (˜15%) of weight prior to recovery. Those vaccinated with NIHGen6HASS-foldon RNA also lost ˜5% body weight. In contrast, mice vaccinated with a combination of NIHGen6HASS-foldon and NP mRNAs appeared to be completely protected from lethal influenza virus challenge, similar to those vaccinated with mRNA expressing an HA antigen homologous to that of the challenge virus (eH1HA). Vaccine efficacy was similar at all vaccine doses, as well as with all co-formulation and co-delivery methods assessed (FIG. 10).


Influenza A challenge #2


This study was designed to test the immunogenicity and efficacy in mice of candidate influenza virus vaccines. Animals tested were 6-8 week old female BALB/c mice obtained from Charles River Laboratories. Test vaccines included the following mRNAs formulated in MC3 LNP: NIHGen6HASS-foldon mRNA (based on Yassine et al. Nat. Med. 2015 September; 21(9):1065-70) and NIHGen6HASS-TM2 mRNA. Control animals were vaccinated with an mRNA encoding the ectodomain of the HA from H1N1 A/Puerto Rico/8/1934 (eH1HA, positive control) or were not vaccinated (naïve).


At week 0 and week 3, animals were immunized intramuscularly (IM) with a total volume of 100 μL of each test vaccine, which was administered in a 50 μL immunization to each quadricep. Candidate influenza virus vaccines evaluated in this study were described above and outlined in the table below. Sera were collected from all animals two weeks after the second dose. At week 6, all animals were challenged intranasally while sedated with a mixture of Ketamine and Xylazine with a lethal dose of mouse-adapted influenza virus strain H1N1 A/Puerto Rico/8/1934. Mortality was recorded and group mouse weight was assessed daily for 20 days post-infection.









TABLE 4







Test Vaccines











Group

Antigen
Formu-
Volume,


#
Antigen
dose
lation
Route





1
NIHGen6HASS-foldon
5 μg
MC3
100 μl, i.m.



RNA





2
NIHGen6HASS-foldon-
5 μg
MC3
100 μl, i.m.



TM2 RNA





3
eH1HA RNA
10 μg 
MC3
100 μl, i.m.


4
Naïve
0 μg
None
None









To test the sera for the presence of antibody capable of binding to hemagglutinin (HA) from a wide variety of influenza strains, ELISA plates were coated with 100 ng of the following recombinant HAs obtained from Sino Biological Inc.: Influenza A H1N1 (A/New Caledonia/20/99), cat #11683-V08H; Influenza A H3N2 (A/Aichi/2/1968), cat #11707-V08H; Influenza A H1N1 (A/California/04/2009) cat #11055-V08H; Influenza A H1N1 (A/Puerto Rico/8/34) cat #11684-V08H; Influenza A H1N1 (A/Brisbane/59/2007), cat #11052-V08H; Influenza A H2N2 (A/Japan/305/1957) cat #11088-V08H; Influenza A H7N9 (A/Anhui/1/2013) cat #40103-V08H and Influenza A H3N2 (A/Moscow/10/99) cat #40154-V08. The ELISA assay was performed and endpoint titers were calculated as described above. FIG. 11A depicts the endpoint titers of the pooled serum from animals vaccinated with the test vaccines. The vaccines tested are shown on the x-axis and the binding to HA from each of the different strains of influenza is plotted. The NIHGen6HASS-foldon mRNA vaccine elicited high titers of antibodies that bound all H1, H2 and H7 HAs tested. The binding titers from NIHGen6HASS-TM2 mRNA vaccinated mice were reduced as compared to those from NIHGen6HASS-foldon mRNA vaccinated mice.


Following lethal challenge with mouse-adapted HIN1 A/Puerto Rico/8/1934, all naïve animals succumbed to infection by day 16 post-infection (FIG. 11B). In contrast, all animals vaccinated with NIHGen6HASS-foldon mRNA, NIHGen6HASS-TM2 mRNA, or eH1HA RNA survived the challenge. As shown in FIG. 11B, the efficacy of the NIHGen6HASS-TM2 vaccine was equivalent to that of the NIHGen6HASS-foldon vaccine.


Influenza A challenge #3


In this example, two animal studies and assays were carried out to evaluate the immune response to influenza virus consensus hemagglutinin (HA) vaccine antigens delivered using an mRNA/LNP platform. The purpose of these studies was to evaluate the ability of consensus HA mRNA vaccine antigens to elicit cross-protective immune responses in the mouse.


To generate consensus HA sequences, 2415 influenza A serotype H1 HA sequences were obtained from the NIAID Influenza Research Database (IRD) (Squires et al., Influenza Other Respir Viruses. 2012 November; 6(6): 404-416) through the web site at www.fludb.org. After removal of duplicate sequences and lab strains, 2385 entries remained, including 1735 H1 sequences from pandemic HIN1 strains (pH1N1) and 650 from seasonal HIN1 strains (sH1N1). Pandemic and seasonal H1 sequences were separately aligned and a consensus sequence was generated for each group using the Matlab 9.0 Bioinformatics toolbox (MathWorks, Natick, MA). Sequence profiles were generated for both groups separately using a modified Seq2Logo program (Thomsen et al., Nucleic Acids Res. 2012 July; 40 (Web Server issue):W281-7).


Animals tested were 6-8 week old female BALB/c mice obtained from Charles River Laboratories. Test vaccines included the following mRNAs formulated in MC3 LNP: ConH1 and ConH3 (based on Webby et al., PLoS One. 2015 Oct. 15; 10(10):e0140702); Cobra_P1 and Cobra_X3 (based on Carter et al., J Virol. 2016 Apr. 14; 90(9):4720-34); MRK_pH1_Con and MRK_sH1_Con (pandemic and seasonal consensus sequences described above); and each of the above mentioned six antigens with a ferritin fusion sequence for potential particle formation.


Controls included: MC3 (control for effects of LNP); Naïve (unvaccinated animals); and vaccination with eH1HA RNA, which encode the ectodomain of HA from strain H1N1 A/PR/8/34 (positive control for the virus challenge).


At week 0 and week 3, animals were immunized intramuscularly (IM) with a total volume of 100 μL of each test vaccine, which was administered in a 50 VL immunization to each quadricep. Candidate influenza virus vaccines evaluated in this study were described above and are outlined in the table below. Sera were collected from all animals two weeks after the second dose (week 5). At week 6, the animals were challenged intranasally while sedated with a mixture of Ketamine and Xylazine with a lethal dose of mouse-adapted influenza virus strain HN1 A/Puerto Rico/8/1934 (PR8). Mortality was recorded and group weight was assessed daily for 20 days post-infection.









TABLE 5







Test Vaccines











Group

Antigen
Formu-
Volume,


#
Antigen
dose
lation
Route





 1
Con_H1 RNA
10 μg
MC3
100 μl, i.m.


 2
Con_H3 RNA
10 μg
MC3
100 μl, i.m.


 3
Merck_pH1_Con RNA
10 μg
MC3
100 μl, i.m.


 4
Merck_sH1_Con RNA
10 μg
MC3
100 μl, i.m.


 5
Cobra_P1 RNA
10 μg
MC3
100 μl, i.m.


 6
Cobra_X3 RNA
10 μg
MC3
100 μl, i.m.


 7
ConH1_ferritin RNA
10 μg
MC3
100 μl, i.m.


 8
ConH3_ferritin RNA
10 μg
MC3
100 μl, i.m.


 9
Merck_pH1_Con_ferritin
10 μg
MC3
100 μl, i.m.



RNA





10
Merck_sH1_Con_ferritin
10 μg
MC3
100 μl, i.m.



RNA





11
Cobra_P1_ferritin RNA
10 μg
MC3
100 μl, i.m.


12
Cobra_X3_ferritin RNA
10 μg
MC3
100 μl, i.m.


13
eH1HA
10 μg
MC3
100 μl, i.m.


14
MC3
 0 μg
MC3
100 μl, i.m.


15
Naïve
 0 μg
None
None









To test the ability of the serum antibodies to neutralize the challenge virus strain, a microneutralization assay using a modified PR8 virus with a Gaussia luciferase reporter gene (Pan et al., Nat Commun. 2013; 4:2369) was performed. Briefly, PR8 luciferase virus was diluted in virus diluent with TPCK-treated trypsin. Serum samples were diluted 1:10 and then serially diluted 3-fold in 96-well cell culture plates. 50 μL of each diluted serum sample and an equal volume of diluted virus were mixed in the well and incubated at 37° C. with 5% CO2 for 1 hr before 100 μL of MDCK cells at 1.5×10∧5 cells/mL were added. Plates were then incubated at 37° C. with 5% CO2 for 72 hrs. Luminescence signal was read with a Gaussia Luciferase Glow Assay Kit (Pierce) on an EnVision reader (Perkin Elmer). As shown in FIG. 12A, serum from mice immunized with mRNA encoding consensus HA antigens from the H1 subtype was able to detectably neutralize the PR8 luciferase virus, even though the HA sequences of these antigens were 8-19% different from that of the PR8 strain. The HA sequence-matched antigen (eH1HA) elicited a much higher serum neutralizing antibody response against this virus. Serum from mice vaccinated with RNA encoding the consensus H3 antigen (ConH3), in contrast, was not able to neutralize the PR8 luciferase virus, suggesting that the consensus sequences from different subtypes (H1 and H3, for example) may not cross-react. Similarly, serum from mice immunized with mRNA encoding H1 subtype consensus HA antigens with a ferritin fusion sequence was able to detectably neutralize the PR8 luciferase virus, except for the Merck_pH1_Con_ferritin mRNA, while serum from mice vaccinated with an mRNA encoding the consensus H3 antigen with a ferritin fusion sequence was not able to neutralize the PR8 luciferase virus (FIG. 12B). Consistent with the serum neutralization data, mice immunized with the consensus H1 HA antigens (with or without ferritin fusion) survived the lethal PR8 virus challenge and showed no weight loss, except for the Merck_pH1_Con_ferritin mRNA group, while mice in the ConH3, naïve and LNP only control groups rapidly lost weight upon challenge (FIG. 13). Mice immunized with Merck_pH1_Con_ferritin mRNA survived the lethal PR8 virus challenge and showed 5-10% weight loss, suggesting that partial protection may be mediated by mechanism(s) other than virus neutralization.


To assess the breadth of the serum neutralizing activity elicited by the consensus HA antigens, neutralization assays were performed on a panel of pseudoviruses as described above (FIG. 14). As expected, serum from mice immunized with influenza virus H1N1 A/Puerto Rico/8/1934 (from studies described in Example 12) was only able to neutralize a matched pseudovirus strain (PR8). In contrast, serum from mice immunized with the consensus H1 HA antigens, as well as the eH1HA antigen, were able to neutralize a panel of diverse group 1 pseudoviruses, including strains from subtypes H1 and H5, but not a strain from group 2 (subtype H3). Consistently, serum from mice immunized with the consensus H3 HA antigen was able to neutralize a strain from group 2 (subtype H3) but not any of the group 1 pseudoviruses.


Influenza B Challenge


This study was designed to test the immunogenicity and efficacy in mice of candidate influenza virus vaccines. Animals tested were 6-8 week old female BALB/c mice obtained from Charles River Laboratories. Test vaccines included the following mRNAs formulated in MC3 LNP: B/Phuket/3073/2013 sHA (soluble HA), B/Phuket/3073/2013 mHA (full-length HA with membrane anchor), B/Brisbane/60/2008 sHA, B/Victoria/02/1987 sHA, B/Victoria/02/1987 mHA, B/Yamagata/16/1988 mHA, or BHA10 (HA stem design). Control animals were vaccinated with a nonlethal dose of mouse-adapted B/Ann Arbor/1954 (positive control) or empty MC3 LNP (to control for effects of the LNP) or were not vaccinated (naïve).


At week 0 and week 3, animals were immunized intramuscularly (IM) with a total volume of 100 μL of each test vaccine, which was administered in a 50 μL immunization to each quadricep. Candidate influenza virus vaccines evaluated in this study were described above and are outlined in the table below. Sera were collected from all animals two weeks after the second dose. At week 6, all animals (n=10 per group) were challenged intranasally while sedated with a mixture of Ketamine and Xylazine with a lethal dose of mouse-adapted influenza virus strain B/Ann Arbor/1954. Mortality was recorded and group mouse weight was assessed daily for 20 days post-infection.


Each of the sequences described herein encompasses a chemically modified sequence or an unmodified sequence which includes no nucleotide modifications.









TABLE 6







Test Vaccines











Group

Antigen
Formu-
Volume,


#
Antigen
dose
lation
Route





 1
B/Phuket/3073/2013
10 μg
MC3
100 μl, i.m.



sHA RNA





 2
B/Phuket/3073/2013
10 μg
MC3
100 μl, i.m.



mHA RNA





 3
B/Brisbane/60/2008
10 μg
MC3
100 μl, i.m.



sHA RNA





 4
B/Victoria/02/1987
10 μg
MC3
100 μl, i.m.



sHA RNA





 5
B/Victoria/02/1987
10 μg
MC3
100 μl, i.m.



mHA RNA





 6
B/Yamagata/16/1988
10 μg
MC3
100 μl, i.m.



mHA RNA





 7
BHA10 RNA
10 μg
MC3
100 μl, i.m.


 8
MC3
 0 μg
MC3
100 μl, i.m.


 9
Naive
 0 μg
None
100 μl, i.m.


10
B/Ann Arbor/1954
0.1 LD90
None
20 μl, i.n.










FIG. 15A depicts the ELISA endpoint anti-HA antibody titers of the pooled serum from animals vaccinated with the test vaccines. The vaccines tested are shown on the x-axis and the binding to HA from each of the different strains of influenza is plotted. All vaccines tested, except for those derived from B/Phuket/3073/2013 were immunogenic, and serum antibody bound to HA from both B/Yamagata/16/1988 (Yamagata lineage) and B/Florida/4/2006 (Victoria lineage).


Following lethal challenge with mouse-adapted B/Ann Arbor/1954, 90% of MC3-vaccinated and naïve animals succumbed to infection by day 16 post-infection (FIG. 15B). The B/Phuket/3073/2013 sHA and mHA mRNA vaccines showed no efficacy against lethal challenge, and the BHA10 stem mRNA vaccine protected only half of the animals. All other vaccines tested protected mice completely from mortality (FIG. 15B), but only the B/Yamagata/16/1988 mHA RNA vaccine was able to prevent lethality and weight loss in animals challenged with a heterologous virus strain (FIG. 15B).


Example 14: Non-Human Primate Immunogenicity

This study was designed to test the immunogenicity in rhesus macaques of candidate influenza virus vaccines. Test vaccines included the following mRNAs formulated in MC3 LNP: NIHGen6HASS-foldon mRNA (based on Yassine et al. Nat. Med. 2015 September; 21(9):1065-70) and NP mRNA encoding NP protein from an H3N2 influenza strain.


Animals in Group 1 had been previously vaccinated with seasonal inactivated influenza vaccine (FLUZONE®) and were boosted intramuscularly (IM) at day 0 with 300 μg of NIHGen6HASS-foldon mRNA. Animals in Groups 2 and 3 were influenza naïve at the study start and were vaccinated at days 0, 28 and 56 with 300 μg of NIHGen6HASS-foldon mRNA or 300 μg of NP mRNA, respectively. Serum was collected from all animals prior to the study start (day −8) as well as at days 14, 28, 42, 56, 70, 84, 112, 140 and 168.


The NIHGen6HASS-foldon vaccine elicited a robust antibody response as measured by ELISA assay (plates coated with recombinantly-expressed NIHGen6HASS-foldon [HA stem] or NP proteins), and the data is depicted in FIG. 16. FIG. 16A shows titers to HA stem, over time, for four rhesus macaques previously vaccinated with FLUZONE® and boosted a single time with NIHGen6HASS-foldon mRNA vaccine. FIG. 16B depicts titers to HA stem, over time, from four rhesus macaques vaccinated at days 0, 28 and 56 with the same NIHGen6HASS-foldon RNA vaccine. The NIHGen6HASS-foldon RNA vaccine was able to boost anti-HA stem antibody binding titers in animal previously vaccinated with inactivated influenza vaccine as well as elicited a robust response in naïve animals. In both groups, HA stem titers remained elevated over baseline to at least study day 168. FIG. 16C illustrates antibody titers to NP, over time, for four rhesus macaques vaccinated at days 0, 28 and 56 with the NP mRNA vaccine and shows that the vaccine elicited a robust antibody response to NP.


To test the Group 1 and 2 sera for the presence of antibody capable of binding to hemagglutinin (HA) from a wide variety of influenza strains, ELISA plates were coated with recombinant HAs from a diverse set of influenza strains as described above. EC10 titers were calculated as the reciprocal of the serum dilution that reached 10% of the maximal signal. For animals in Group 1 (FIG. 17A), a single dose of NIHGen6HASS-foldon vaccine boosted titers to H1 HAs˜40-60 fold, and titers peaked approximately 28 days post-vaccination. Titers decreased from days 28-70, but day 70 titers were still˜10-30-fold above the titers measured prior to vaccination. The NIHGen6HASS-foldon mRNA vaccine did not boost titers to HAs from H3 or H7 influenza strains. For animals in Group 2 (FIG. 17B), antibody titers to H1 and H2 HAs rose after each dose of NIHGen6HASS-foldon mRNA vaccine, and titers appeared to rise most dramatically after dose 2.


In addition to robust antibody responses, the NP mRNA vaccine also elicited cell-mediated immunity in rhesus. On study day 0, 42, 70 and 140, PBMCs were collected from Group 3 NP mRNA vaccinated rhesus macaques. Lymphocytes were stimulated with a pool of NP peptides, and IFN-γ, IL-2 or TNF-α production were measured by intracellular staining and flow cytometry. FIG. 18 is a representation of responses following NP peptide pool stimulation. Following vaccination with NP mRNA, antigen-specific CD4 and CD8 T cells were found in the peripheral blood, and these cells were maintained above baseline to at least study day 140.


Example 15: H7N9 Immunogenicity Studies

The instant study was designed to test H7N9 immunogenicity. Intramuscular immunizations of 25 μM were administered on days 1 and 22 to 40 animals, and blood was collected on days 1, 8, 22, and 43. Hemagglutination inhibition (HAI) and microneutralization tests were conducted using the blood samples.


The HAI test showed a geometric mean titer (GMT) of 45 for all of the animals, including the placebo group. The GMT of the responders only was 116 (FIG. 19). The HAI kinetics for each individual subject are given in FIG. 20.


The microneutralization (MN) test showed a geometric mean titer (GMT) of 36 for all of the animals, including the placebo group. The GMT of the responders only was 84 (FIG. 21). The MN test kinetics for each subject are given in FIG. 22.


HAI and MN showed a very strong correlation (FIG. 23). Only one subject had a protective titer in one assay, but not in the other. Also, 10 subjects had no detectable HAI or MN titer at Day 43.


Example 16: Mouse Immunogenicity Studies

This study was designed to test the immunogenicity and efficacy in mice of candidate influenza virus vaccines. Animals tested were 6-8 week old female BALB/c mice obtained from Charles River Laboratories. Test vaccines included the following mRNAs formulated in a cationic LNP: MRK_H1_cot_all MRK_H3_cot_all MRK_H3_con_all MRK_H3_Consensus A and MRK_H3_Consensus B. Control animals were vaccinated with an mRNA encoding the HA from HN1 A/Puerto Rico/8/1934 (FLHA_PR8, positive control for PR8 infection), vaccinated with empty LNP, infected with a nonlethal dose of mouse-adapted H3 A/Hong Kong//1968, or were not vaccinated (naïve).


At week 0 and week 3, animals were immunized intramuscularly (IM) with a total volume of 100 mL of each test vaccine, which was administered in a 50 mL immunization to each quadricep. Candidate influenza virus vaccines evaluated in this study were described above and outlined in the table below. Sera were collected from all animals two weeks after the second dose. At week 6, all animals were challenged intranasally while sedated with a mixture of Ketamine and Xylazine with a lethal dose of mouse-adapted influenza virus strain H1N1 A/Puerto Rico/8/1934 (PR8) or H3 A/Hong Kong/l/1968 (HK68). Mortality was recorded and group mouse weight was assessed daily for 20 days post-infection.













TABLE A





Group

Antigen
Formu-
Volume,


#
Antigen
dose
lation
Route







1
FLHA_PR8 RNA
 5 ug
LNP
100 ul, i.m.



(SEQ ID NO: 541)





2
MRK_H1_cot_all RNA
10 ug
LNP
100 ul, i.m.



(SEQ ID NO: 530)





3
MRK_H3_cot_all RNA
10 ug
LNP
100 ul, i.m.



(SEQ ID NO: 534)





4
MRK_H3_con_all_RNA
10 ug
LNP
100 ul, i.m.



(SEQ ID NO: 533)





5
MRK_H3_Consensus A
10 ug
LNP
100 ul, i.m.



RNA (SEQ ID NO: 531)





6
MRK_H3_Consensus B
10 ug
LNP
100 ul, i.m.



RNA (SEQ ID NO: 532)





7
Empty LNP
 0 ug
LNP
100 ul, i.m.


8
Mouse-adapted H3
0.1 LD90
None
20 ul, i.n.



A/Hong Kong/1/1968






virus





9
Naïve
 0 ug
None
None









To assess the breadth of the serum activity elicited by the antigens, hemagglutination inhibition assays (HAI) were performed using a panel of H1N1 and H3N2 influenza viruses (Tables B and C. Briefly, serum samples were treated with receptor destroying enzyme (RDE) for 18-20 hrs at 37° C. before inactivation at 56° C. for 35-45 min RDE-treated sera was then serially diluted in a 96 well plate and mixed with 4 hemagglutinating units of virus. An equal volume of 0.5% turkey red blood cells was added to each well, and plates were incubated at room temperature for 30 min. The highest dilution with no visible agglutination was assigned as the serum titer. While the MRK_H1_cot_all mRNA vaccine elicited titers to only two viruses in the H1 HAI panel (Table B), the MRK_H3_cot_all MRK_H3_con_all MRK_H3_Consensus A and MRK_H3_Consensus B mRNAs induced high HAI titers to multiple H3 strains isolated between 1997 and 2014 (Table a.


Although mice immunized with MRK_H1_cot_all mRNA did not have detectable HAI titers to the PR8 virus, they were partially protected from lethal challenge with PR8 virus. In contrast to naïve or LNP vaccinated mice, all MRK_H1_cot_all mRNA immunized mice survived challenge (FIG. 24A), though they lost, on average, approximately 10% of their body weight post-infection (FIG. 24B). Similarly, mice vaccinated with any of the H3 COT or consensus mRNAs tested survived challenge with a lethal dose of HK68 virus (FIG. 24C) but lost between 10 and 15% or their body weight post-infection (FIG. 24D).















TABLE B








A/Puerto
A/Fort/Monmouth/
A/New
A/Brazil/
A/Singapore/
A/Texas/


Vaccine
Rico/8/1934
1/1947
Jersey/10/1976
11/1978
6/1986
36/1991





MRK_H1_cot_all
<10
<10
2,560
<10
<10
<10


Naive
<10
<10
<10
<10
<10
<10






A/Beijing/
A/New
A/Solomon
A/Brisbane/
A/California/



Vaccine
262/1995
Caledonia/20/1999
Islands/3/2006
59/2007
07/2009






MRK_H1_cot_all
<10
<10
<10
<10
10,240



Naive
<10
<10
<10
<10
<10























TABLE C






A/HongKong/
A/Philippines/
A/Sydney/
A/Texas/
A/Switzerland/
A/HongKong/


Vaccine
1/1968
1982
5/1997
50/2012
9715293/2013
4801/2014





















H3_cot_all
<10
<10
<10
40,960
20,480
10,240


MRK_H3_con_all
<10
<10
<10
40,960
10,240
10,240


MRK_H3_ConA
<10
<10
10,240
640
320
20


MRK_H3_ConB
<10
<10
<10
40,960
10,240
10,240


Naive
<10
<10
<10
<10
<10
<10
















TABLE 7







Influenza H1N1 Antigens











GenBank/GI


Strain/Protein
Length
Accession No.





Influenza A virus (A/Bayern/7/95(H1N1)) NA
1,459 bp
AJ518104.1


gene for neuraminidase, genomic RNA
linear mRNA
GI: 31096418


Influenza A virus (A/Brazil/11/1978(X-
1,072 bp
X86654.1


71)(H1N1)) mRNA for hemagglutinin HA1, escape
linear mRNA
GI: 995549


variant 1




Influenza A virus (A/Brazil/11/1978(X-
1,072 bp
X86655.1


71)(H1N1)) mRNA for hemagglutinin HA1, escape
linear mRNA
GI: 995550


variant 2




Influenza A virus (A/Brazil/11/1978(X-
1,072 bp
X86656.1


71)(H1N1)) mRNA for hemagglutinin HA1, escape
linear mRNA
GI: 995551


variant 3




Influenza A virus (A/Brazil/11/1978(X-
1,072 bp
X86657.1


71)(H1N1)) mRNA for hemagglutinin HA1, escape
linear mRNA
GI: 995552


variant 4




Influenza A virus
1,220 bp
AF116575.1


(A/Brevig_Mission/1/18(H1N1)) hemagglutinin
linear mRNA
GI: 4325017


(HA) mRNA, partial cds




Influenza A virus
1,410 bp
AF250356.2


(A/Brevig_Mission/1/18(H1N1)) neuraminidase
linear mRNA
GI: 13260556


(NA) gene, complete cds




Influenza A virus (A/Brevig
1,497 bp
AY744935.1


Mission/1/1918(H1N1)) nucleoprotein (np)
linear mRNA
GI: 55273940


mRNA, complete cds




Influenza A virus (A/Brevig
2,280 bp
DQ208309.1


Mission/1/1918(H1N1)) polymerase PB2 (PB2)
linear mRNA
GI: 76786704


mRNA, complete cds




Influenza A virus (A/Brevig
2,274 bp
DQ208310.1


Mission/1/1918(H1N1)) polymerase PB1 (PB1)
linear mRNA
GI: 76786706


mRNA, complete cds




Influenza A virus (A/Brevig
2,151 bp
DQ208311.1


Mission/1/1918(H1N1)) polymerase PA (PA)
linear mRNA
GI: 76786708


mRNA, complete cds




Influenza A virus
366 bp
M73975.1


(A/camel/Mongolia/1982(H1N1)) hemagglutinin
linear mRNA
GI: 324242


mRNA, partial cds




Influenza A virus
460 bp
M73978.1


(A/camel/Mongolia/1982(H1N1)) matrix protein
linear mRNA
GI: 324402


mRNA, partial cds




Influenza A virus
310 bp
M73976.1


(A/camel/Mongolia/1982(H1N1)) neuraminidase
linear mRNA
GI: 324579


(NA) mRNA, partial cds




Influenza A Virus A/camel/Mongolia/82 NS1
273 bp
M73977.1


protein mRNA, partial cds
linear mRNA
GI: 324768


Influenza A virus
227 bp
M73974.1


(A/camel/Mongolia/1982(H1N1)) PA polymerase
linear mRNA
GI: 324931


mRNA, partial cds




Influenza A virus
531 bp
M73973.1


(A/camel/Mongolia/1982(H1N1)) PB1 protein
linear mRNA
GI: 324971


mRNA, partial cds




Influenza A Virus (A/camel/Mongolia/82(H1N1))
379 bp
M73972.1


polymerase 2 (P2) mRNA, partial cds
linear mRNA
GI: 324993


Influenza A virus (A/chicken/Hong
1,169 bp
U46782.1


Kong/14/1976(H1N1)) hemagglutinin precursor
linear mRNA
GI: 1912328


(HA) mRNA, partial cds




Influenza A virus (A/Chonnam/07/2002(H1N1))
1,452 bp
AY297141.1


neuraminidase (NA) mRNA, complete cds
linear mRNA
GI: 31871990


Influenza A virus (A/Chonnam/07/2002(H1N1))
1,137 bp
AY297154.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32140347


Influenza A virus (A/Chonnam/18/2002(H1N1))
1,458 bp
AY297143.1


neuraminidase (NA) mRNA, complete cds
linear mRNA
GI: 31871994


Influenza A virus (A/Chonnam/18/2002(H1N1))
1,176 bp
AY297156.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32140355


Influenza A virus (A/Chonnam/19/2002(H1N1))
1,458 bp
AY310410.1


neuraminidase (NA) mRNA, complete cds
linear mRNA
GI: 31872389


Influenza A virus (A/Chonnam/19/2002(H1N1))
1,167 bp
AY299502.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32140392


Influenza A virus (A/Chonnam/51/2002(H1N1))
1,443 bp
AY310412.1


neuraminidase (NA) mRNA, complete cds
linear mRNA
GI: 31873090


Influenza A virus (A/Chonnam/51/2002(H1N1))
1,161 bp
AY299498.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32140384


Influenza A virus (A/Chungbuk/50/2002(H1N1))
1,425 bp
AY297150.1


neuraminidase (NA) mRNA, partial cds
linear mRNA
GI: 31872010


Influenza A virus (A/Chungbuk/50/2002(H1N1))
1,161 bp
AY299506.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32140400


Influenza A virus (A/Denmark/40/2000(H1N1))
1,458 bp
AJ518095.1


NA gene for neuraminidase, genomic RNA
linear mRNA
GI: 31096400


Influenza A virus (A/Denver/1/57(H1N1))
379 bp
AF305216.1


neuraminidase mRNA, partial cds
linear mRNA
GI: 10732818


Influenza A virus (A/Denver/1/57(H1N1))
442 bp
AF305217.1


matrix protein gene, partial cds
linear mRNA
GI: 10732820


Influenza A virus (A/Denver/1/57(H1N1))
215 bp
AF305218.1


hemagglutinin gene, partial cds
linear mRNA
GI: 10732822


Influenza A virus
981 bp
U47309.1


(A/duck/Australia/749/80(H1N1)) hemagglutinin
linear mRNA
GI: 1912348


precursor (HA) mRNA, partial cds




Influenza A virus
1,777 bp
AF091312.1


(A/duck/Australia/749/80(H1N1)) segment 4
linear mRNA
GI: 4585166


hemagglutinin precursor (HA) mRNA, complete




cds




Influenza A virus (A/duck/Bavaria/1/77
1,777 bp
AF091313.1


(H1N1)) segment 4 hemagglutinin precursor
linear mRNA
GI: 4585168


(HA) mRNA, complete cds




Influenza A virus (A/duck/Bavaria/2/77(H1N1))
981 bp
U47308.1


hemagglutinin precursor (HA) mRNA, partial
linear mRNA
GI: 1912346


cds




Influenza A virus (A/duck/Eastern
1,458 bp
EU429749.1


China/103/2003(H1N1)) segment 6 neuraminidase
linear mRNA
GI: 167859463


(NA) mRNA, complete cds




Influenza A virus (A/duck/Eastern
1,461 bp
EU429751.1


China/152/2003(H1N1)) segment 6 neuraminidase
linear mRNA
GI: 167859467


(NA) mRNA, complete cds




Influenza A virus (A/Duck/Ohio/118C/93
1,410 bp
AF250361.2


(H1N1)) neuraminidase (NA) gene, complete cds
linear mRNA
GI: 13260576


Influenza A virus (A/Duck/Ohio/175/86 (H1N1))
1,410 bp
AF250358.2


neuraminidase (NA) gene, complete cds
linear mRNA
GI: 13260565


Influenza A virus (A/Duck/Ohio/194/86 (H1N1))
1,410 bp
AF250360.2


neuraminidase (NA) gene, complete cds
linear mRNA
GI: 13260573


Influenza A virus (A/Duck/Ohio/30/86 (H1N1))
1,410 bp
AF250359.2


neuraminidase (NA) gene, complete cds
linear mRNA
GI: 13260570


Influenza A virus strain
1,460 bp
AJ006954.1


A/Fiji/15899/83(H1N1) mRNA for neuraminidase
linear mRNA
GI: 4210707


Influenza A Virus (A/Fiji/15899/83(H1N1))
2,341 bp
AJ564805.1


mRNA for PB2 protein
linear mRNA
GI: 31442134


Influenza A Virus (A/Fiji/15899/83(H1N1))
2,113 bp
AJ564807.1


partial mRNA for PB1 protein
linear mRNA
GI: 31442138


Influenza A virus (A/FM/1/47 (H1N1))
1,395 bp
AF250357.2


neuraminidase (NA) gene, complete cds
linear mRNA
GI: 13260561


Influenza A virus (A/goose/Hong
1,091 bp
U46021.1


Kong/8/1976(H1N1)) hemagglutinin precursor
linear mRNA
GI: 1912326


(HA) mRNA, partial cds




Influenza A virus (A/goose/Hong
261 bp
U48284.1


Kong/8/1976(H1N1)) polymerase (PB1) mRNA,
linear mRNA
GI: 1912372


partial cds




Influenza A virus (A/goose/Hong
1,395 bp
U49093.1


Kong/8/1976(H1N1)) nucleoprotein (NP) mRNA,
linear mRNA
GI: 1912384


partial cds




Influenza A virus
1,775 bp
EU382986.1


(A/Guangzhou/1561/2006(H1N1)) segment 4
linear mRNA
GI: 170762603


hemagglutinin (HA) mRNA, complete cds




Influenza A virus
1,462 bp
EU382993.1


(A/Guangzhou/1561/2006(H1N1)) segment 6
linear mRNA
GI: 170762617


neuraminidase (NA) mRNA, complete cds




Influenza A virus
1,775 bp
EU382987.1


(A/Guangzhou/1684/2006(H1N1)) segment 4
linear mRNA
GI: 170762605


hemagglutinin (HA) mRNA, complete cds




Influenza A virus
1,462 bp
EU382994.1


(A/Guangzhou/1684/2006(H1N1)) segment 6
linear mRNA
GI: 170762619


neuraminidase (NA) mRNA, complete cds




Influenza A virus
1,775 bp
EU382981.1


(A/Guangzhou/483/2006(H1N1)) segment 4
linear mRNA
GI: 170762593


hemagglutinin (HA) mRNA, complete cds




Influenza A virus
1,462 bp
EU382988.1


(A/Guangzhou/483/2006(H1N1)) segment 6
linear mRNA
GI: 170762607


neuraminidase (NA) mRNA, complete cds




Influenza A virus
1,775 bp
EU382982.1


(A/Guangzhou/506/2006(H1N1)) segment 4
linear mRNA
GI: 170762595


hemagglutinin (HA) mRNA, complete cds




Influenza A virus
1,461 bp
EU382989.1


(A/Guangzhou/506/2006(H1N1)) segment 6
linear mRNA
GI: 170762609


neuraminidase (NA) mRNA, complete cds




Influenza A virus
1,775 bp
EU382983.1


(A/Guangzhou/555/2006(H1N1)) segment 4
linear mRNA
GI: 170762597


hemagglutinin (HA) mRNA, complete cds




Influenza A virus
1,462 bp
EU382990.1


(A/Guangzhou/555/2006(H1N1)) segment 6
linear mRNA
GI: 170762611


neuraminidase (NA) mRNA, complete cds




Influenza A virus
1,775 bp
EU382984.1


(A/Guangzhou/657/2006(H1N1)) segment 4
linear mRNA
GI: 170762599


hemagglutinin (HA) mRNA, complete cds




Influenza A virus
1,462 bp
EU382991.1


(A/Guangzhou/657/2006(H1N1)) segment 6
linear mRNA
GI: 170762613


neuraminidase (NA) mRNA, complete cds




Influenza A virus
1,775 bp
EU382985.1


(A/Guangzhou/665/2006(H1N1)) segment 4
linear mRNA
GI: 170762601


hemagglutinin (HA) mRNA, complete cds




Influenza A virus
1,462 bp
EU382992.1


(A/Guangzhou/665/2006(H1N1)) segment 6
linear mRNA
GI: 170762615


neuraminidase (NA) mRNA, complete cds




Influenza A virus (A/Gwangju/55/2002(H1N1))
1,431 bp
AY297151.1


neuraminidase (NA) mRNA, complete cds
linear mRNA
GI: 31872012


Influenza A virus (A/Gwangju/55/2002(H1N1))
1,179 bp
AY299507.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32140402


Influenza A virus (A/Gwangju/57/2002(H1N1))
1,446 bp
AY297152.1


neuraminidase (NA) mRNA, complete cds
linear mRNA
GI: 31872014


Influenza A virus (A/Gwangju/57/2002(H1N1))
1,167 bp
AY299508.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32140404


Influenza A virus (A/Gwangju/58/2002(H1N1))
1,434 bp
AY297153.1


neuraminidase (NA) mRNA, complete cds
linear mRNA
GI: 31872016


Influenza A virus (A/Gwangju/58/2002(H1N1))
1,176 bp
AY299509.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32140406


Influenza A virus (A/Gwangju/90/2002(H1N1))
1,446 bp
AY297147.1


neuraminidase (NA) mRNA, complete cds
linear mRNA
GI: 31872002


Influenza A virus (A/Gwangju/90/2002(H1N1))
1,164 bp
AY299499.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32140386


Influenza A virus (A/Hong
1,403 bp
AJ518101.1


Kong/437/2002(H1N1)) partial NA gene for
linear mRNA
GI: 31096412


neuraminidase, genomic RNA




Influenza A virus (A/Hong
1,352 bp
AJ518102.1


Kong/747/2001(H1N1)) partial NA gene for
linear mRNA
GI: 31096414


neuraminidase, genomic RNA




Influenza A virus (A/London/1/1918(H1N1))
563 bp
AY184805.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32395285


Influenza A virus (A/London/1/1919(H1N1))
563 bp
AY184806.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32395287


Influenza A virus (A/Loygang/4/1957(H1N1))
1,565 bp
M76604.1


nucleoprotein mRNA, complete cds
linear mRNA
GI: 324255


Influenza A virus (A/Lyon/651/2001(H1N1))
1,318 bp
AJ518103.1


partial NA gene for neuraminidase, genomic
linear mRNA
GI: 31096416


RNA




Influenza A virus (A/mallard/Alberta/119/98
947 bp
AY664487.1


(H1N1)) nonfunctional matrix protein mRNA,
linear mRNA
GI: 51011891


partial sequence




Influenza A virus
981 bp
U47310.1


(A/duck/Alberta/35/76(H1N1)) hemagglutinin
linear mRNA
GI: 1912350


precursor (HA) mRNA, partial cds




Influenza A virus
1,777 bp
AF091309.1


(A/duck/Alberta/35/76(H1N1)) segment 4
linear mRNA
GI: 4585160


hemagglutinin precursor (HA) mRNA, complete




cds




Influenza A virus
1,410 bp
AF250362.2


(A/duck/Alberta/35/76(H1N1)) neuraminidase
linear mRNA
GI: 13260579


(NA) gene, complete cds




Influenza A virus
981 bp
U47307.1


(A/mallard/Tennessee/11464/85 (H1N1))
linear mRNA
GI: 1912344


hemagglutinin precursor (HA) mRNA, partial




cds




Influenza A virus
1,777 bp
AF091311.1


(A/mallard/Tennessee/11464/85 (H1N1)) segment
linear mRNA
GI: 4585164


4 hemagglutinin precursor (HA) mRNA, complete




cds




Influenza A virus (A/New
294 bp
HQ008884.1


Caledonia/20/1999(H1N1)) segment 7 matrix
linear mRNA
GI: 302566794


protein 2 (M2) mRNA, complete cds




Influenza A virus (A/New Jersey/4/1976(H1N1))
1,565 bp
M76605.1


nucleoprotein mRNA, complete cds
linear mRNA
GI: 324581


Influenza A virus (A/New Jersey/8/1976(H1N1))
1,565 bp
M76606.1


nucleoprotein mRNA, complete cds
linear mRNA
GI: 324583


Influenza A virus (A/New_York/1/18(H1N1))
1,220 bp
AF116576.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 4325019


Influenza A virus (A/Ohio/3523/1988(H1N1))
1,565 bp
M76602.1


nucleoprotein mRNA, complete cds
linear mRNA
GI: 324889


Influenza A virus (A/Pusan/22/2002(H1N1))
1,455 bp
AY310411.1


neuraminidase (NA) mRNA, complete cds
linear mRNA
GI: 31872391


Influenza A virus (A/Pusan/22/2002(H1N1))
1,149 bp
AY299503.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32140394


Influenza A virus (A/Pusan/23/2002(H1N1))
1,440 bp
AY297144.1


neuraminidase (NA) mRNA, complete cds
linear mRNA
GI: 31871996


Influenza A virus (A/Pusan/23/2002(H1N1))
1,158 bp
AY297157.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32140357


Influenza A virus (A/Pusan/24/2002(H1N1))
1,449 bp
AY297145.1


neuraminidase (NA) mRNA, complete cds
linear mRNA
GI: 31871998


Influenza A virus (A/Pusan/24/2002(H1N1))
1,128 bp
AY299494.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32140376


Influenza A virus (A/Pusan/44/2002(H1N1))
1,431 bp
AY297148.1


neuraminidase (NA) mRNA, complete cds
linear mRNA
GI: 31872004


Influenza A virus (A/Pusan/44/2002(H1N1))
1,167 bp
AY299504.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32140396


Influenza A virus (A/Pusan/45/2002(H1N1))
1,434 bp
AY297146.1


neuraminidase (NA) mRNA, complete cds
linear mRNA
GI: 31872000


Influenza A virus (A/Pusan/45/2002(H1N1))
1,167 bp
AY299496.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32140380


Influenza A virus (A/Pusan/46/2002(H1N1))
1,422 bp
AY310408.1


neuraminidase (NA) mRNA, complete cds
linear mRNA
GI: 31872385


Influenza A virus (A/Pusan/46/2002(H1N1))
1,176 bp
AY299497.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32140382


Influenza A virus (A/Pusan/47/2002(H1N1))
1,437 bp
AY297149.1


neuraminidase (NA) mRNA, complete cds
linear mRNA
GI: 31872008


Influenza A virus (A/Pusan/47/2002(H1N1))
1,170 bp
AY299505.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32140398


Influenza A virus (A/Saudi
789 bp
AJ519463.1


Arabia/7971/2000(H1N1)) partial NS1 gene for
linear mRNA
GI: 31096450


non structural protein 1 and partial NS2 gene




for non structural protein 2, genomic RNA




Influenza A virus (A/Seoul/11/2002(H1N1))
1,452 bp
AY297142.1


neuraminidase (NA) mRNA, complete cds
linear mRNA
GI: 31871992


Influenza A virus (A/Seoul/11/2002(H1N1))
1,176 bp
AY297155.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32140349


Influenza A virus (A/Seoul/13/2002(H1N1))
1,452 bp
AY310409.1


neuraminidase (NA) mRNA, complete cds
linear mRNA
GI: 31872387


Influenza A virus (A/Seoul/13/2002(H1N1))
1,167 bp
AY299500.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32140388


Influenza A virus (A/Seoul/15/2002(H1N1))
1,449 bp
AY297140.1


neuraminidase (NA) mRNA, complete cds
linear mRNA
GI: 31871988


Influenza A virus (A/Seoul/15/2002(H1N1))
1,149 bp
AY299501.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32140390


Influenza A virus (A/Seoul/33/2002(H1N1))
1,437 bp
AY310407.1


neuraminidase (NA) mRNA, complete cds
linear mRNA
GI: 31872383


Influenza A virus (A/Seoul/33/2002(H1N1))
1,167 bp
AY299495.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32140378


Influenza A virus
1,050 bp
Z46437.1


(A/swine/Arnsberg/6554/1979(H1N1)) mRNA for
linear mRNA
GI: 565609


hemagglutinin HA1




Influenza A virus
1,595 bp
U46783.1


(A/swine/Beijing/47/1991(H1N1)) hemagglutinin
linear mRNA
GI: 1912330


precursor (HA) mRNA, partial cds




Influenza A virus
1,565 bp
U49091.1


(A/swine/Beijing/94/1991(H1N1)) nucleoprotein
linear mRNA
GI: 1912380


(NP) mRNA, complete cds




Influenza A virus
1,778 bp
AF091316.1


(A/swine/Belgium/1/83(H1N1)) segment 4
linear mRNA
GI: 4585174


hemagglutinin precursor (HA) mRNA, complete




cds




Influenza A virus (A/swine/Cotes
1,116 bp
AM490219.1


d'Armor/0118/2006(H1N1)) partial mRNA for
linear mRNA
GI: 222062898


haemagglutinin precursor (HA1 gene)




Influenza A virus (A/swine/Cotes
1,043 bp
AM490223.1


d'Armor/013618/2006(H1N1)) partial mRNA for
linear mRNA
GI: 222062906


haemagglutinin precursor (HA1 gene)




Influenza A virus (A/swine/Cotes
1,089 bp
AM490220.1


d'Armor/0184/2006(H1N1)) partial mRNA for
linear mRNA
GI: 222062900


haemagglutinin precursor (HA1 gene)




Influenza A virus (A/swine/Cotes
1,068 bp
AM490221.1


d'Armor/0227/2005(H1N1)) partial mRNA for
linear mRNA
GI: 222062902


haemagglutinin precursor (HA1 gene)




Influenza A virus (A/swine/Cotes
1,024 bp
AM490222.1


d'Armor/0250/2006(H1N1)) partial mRNA for
linear mRNA
GI: 222062904


haemagglutinin precursor (HA1 gene)




Influenza A virus (A/swine/Cotes
1,011 bp
AJ517820.1


d'Armor/736/2001(H1N1)) partial HA gene for
linear mRNA
GI: 38422533


Haemagglutinin, genomic RNA




Influenza A virus (A/Swine/England/195852/92
1,410 bp
AF250366.2


(H1N1)) neuraminidase (NA) gene, complete cds
linear mRNA
GI: 13260593


Influenza A virus PB2 gene for Polymerase 2
2,268 bp
AJ311457.1


protein, genomic RNA, strain
linear mRNA
GI: 13661037


A/Swine/Finistere/2899/82




Influenza A virus PB1 gene for Polymerase 1
2,341 bp
AJ311462.1


protein, genomic RNA, strain
linear mRNA
GI: 13661047


A/Swine/Finistere/2899/82




Influenza A virus PA gene for Polymerase A
2,233 bp
AJ311463.1


protein, genomic RNA, strain
linear mRNA
GI: 13661049


A/Swine/Finistere/2899/82




Influenza A virus
1,002 bp
AJ316059.1


(A/swine/Finistere/2899/82(H1N1) M1 gene for
linear mRNA
GI: 20068128


matrix protein 1 and M2 gene for matrix




protein 2, genomic RNA




Influenza A virus
864 bp
AJ344037.1


(A/swine/Finistere/2899/82(H1N1)) NS1 gene
linear mRNA
GI: 20068185


for non structural protein 1 and NS2 gene for




non structural protein 2, genomic RNA




Influenza A virus
838 bp
X75786.1


(A/swine/Germany/2/1981(H1N1)) mRNA for PA
linear mRNA
GI: 438106


polymerase




Influenza A virus
305 bp
Z30277.1


(A/swine/Germany/2/1981(H1N1)) mRNA for
linear mRNA
GI: 530399


neuraminidase (partial)




Influenza A virus
1,730 bp
Z30276.1


(A/swine/Germany/2/1981(H1N1)) mRNA for
linear mRNA
GI: 563490


hemagglutinin




165. Influenza A virus
1,730 bp
Z46434.1


(A/swine/Germany/8533/1991(H1N1)) mRNA for
linear mRNA
GI: 565611


hemagglutinin precursor




Influenza A virus
1,690 bp
AY852271.1


(A/swine/Guangdong/711/2001(H1N1))
linear mRNA
GI: 60327789


nonfunctional hemagglutinin (HA) mRNA,




partial sequence




Influenza A virus
1,809 bp
EU163946.1


(A/swine/Haseluenne/IDT2617/03(H1N1))
linear mRNA
GI: 157679548


hemagglutinin mRNA, complete cds




Influenza A virus (A/swine/Hokkaido/2/81
981 bp
U47306.1


(H1N1)) hemagglutinin precursor (HA) mRNA,
linear mRNA
GI: 1912342


partial cds




Influenza A virus (A/swine/Hokkaido/2/81
1,778 bp
AF091306.1


(H1N1)) segment 4 hemagglutinin precursor
linear mRNA
GI: 4585154


(HA) mRNA, complete cds




Influenza A virus (A/swine/Hong
1,113 bp
U44482.1


Kong/168/1993(H1N1)) hemagglutinin precursor
linear mRNA
GI: 1912318


(HA) mRNA, partial cds




Influenza A virus (A/swine/Hong
416 bp
U47817.1


Kong/168/1993(H1N1)) neuraminidase (NA) mRNA,
linear mRNA
GI: 1912354


partial cds




Influenza A virus (A/swine/Hong
286 bp
U48286.1


Kong/168/1993(H1N1)) polymerase (PB2) mRNA,
linear mRNA
GI: 1912358


partial cds




Influenza A virus (A/swine/Hong
379 bp
U48283.1


Kong/168/1993(H1N1)) polymerase (PB1) mRNA,
linear mRNA
GI: 1912370


partial cds




Influenza A virus (A/swine/Hong
308 bp
U48850.1


Kong/168/1993(H1N1)) polymerase (PA) mRNA,
linear mRNA
GI: 1912376


partial cds




Influenza A virus (A/swine/Hong
1,397 bp
U49096.1


Kong/168/1993(H1N1)) nucleoprotein (NP) mRNA,
linear mRNA
GI: 1912390


partial cds




Influenza A virus (A/swine/Hong
1,315 bp
U46020.1


Kong/172/1993(H1N1)) hemagglutinin precursor
linear mRNA
GI: 1912324


(HA) mRNA, partial cds




Influenza A virus (A/swine/Hong
1,113 bp
U45451.1


Kong/176/1993(H1N1)) hemagglutinin precursor
linear mRNA
GI: 1912320


(HA) mRNA, partial cds




Influenza A virus (A/swine/Hong
1,330 bp
U45452.1


Kong/273/1994(H1N1)) hemagglutinin precursor
linear mRNA
GI: 1912322


(HA) mRNA, partial cds




Influenza A virus (A/swine/Hong
241 bp
U47818.1


Kong/273/1994(H1N1)) neuraminidase (NA) mRNA,
linear mRNA
GI: 1912356


partial cds




Influenza A virus (A/swine/Hong
328 bp
U48287.1


Kong/273/1994(H1N1)) polymerase (PB2) mRNA,
linear mRNA
GI: 1912360


partial cds




Influenza A virus (A/swine/Hong
240 bp
U48282.1


Kong/273/1994(H1N1)) polymerase (PB1) mRNA,
linear mRNA
GI: 1912368


partial cds




Influenza A virus (A/swine/Hong
336 bp
U48851.1


Kong/273/1994(H1N1)) polymerase (PA) mRNA,
linear mRNA
GI: 1912378


partial cds




Influenza A virus (A/swine/Hong
1,422 bp
U49092.1


Kong/273/1994(H1N1)) nucleoprotein (NP) mRNA,
linear mRNA
GI: 1912382


partial cds




Influenza A virus
1,761 bp
EU163947.1


(A/swine/IDT/Re230/92hp(H1N1)) hemagglutinin
linear mRNA
GI: 157679550


mRNA, complete cds




Influenza A virus
1,550 bp
L46849.1


(A/swine/IN/1726/1988(H1N1)) nucleoprotein
linear mRNA
GI: 954755


(segment 5) mRNA, complete cds




Influenza A virus (A/swine/Iowa/15/30(H1N1))
981 bp
U47305.1


hemagglutinin precursor (HA) mRNA, partial
linear mRNA
GI: 1912340


cds




Influenza A virus (A/swine/Iowa/15/30 (H1N1))
1,778 bp
AF091308.1


segment 4 hemagglutinin precursor (HA) mRNA,
linear mRNA
GI: 4585158


complete cds




Influenza A virus (A/Swine/Iowa/30 (H1N1))
1,410 bp
AF250364.2


neuraminidase (NA) gene, complete cds
linear mRNA
GI: 13260586


Influenza A virus (A/swine/Iowa/17672/88
981 bp
U47304.1


(H1N1)) hemagglutinin precursor (HA) mRNA,
linear mRNA
GI: 1912338


partial cds




Influenza A virus
864 bp
AJ519462.1


(A/swine/Italy/3364/00(H1N1)) partial NS1
linear mRNA
GI: 31096447


gene for non structural protein 1 and partial




NS2 gene for non structural protein 2,




genomic RNA




Influenza A virus (A/swine/Italy-
1,777 bp
AF091315.1


Virus/671/87(H1N1)) segment 4 hemagglutinin
linear mRNA
GI: 4585172


precursor (HA) mRNA, complete cds




Influenza A Virus
1,028 bp
Z46436.1


(A/swine/Italy/v.147/1981(H1N1)) mRNA for
linear mRNA
GI: 854214


hemagglutinin HA1




Influenza A virus
1,118 bp
AM490218.1


(A/swine/Morbihan/0070/2005(H1N1)) partial
linear mRNA
GI: 222062896


mRNA for haemagglutinin precursor (HA1 gene)




Influenza A virus
1,770 bp
L09063.1


(A/swine/Nebraska/1/92(H1N1)) HA protein
linear mRNA
GI: 290722


mRNA, complete cds




Influenza A virus
1,550 bp
L11164.1


(A/swine/Nebraska/1/1992(H1N1)) segment 5
linear mRNA
GI: 290724


nucleoprotein (NP) mRNA, complete cds




Influenza A virus
981 bp
U46943.1


(A/swine/Netherlands/12/1985(H1N1))
linear mRNA
GI: 1912336


hemagglutinin (HA) mRNA, partial cds




Influenza A virus
1,776 bp
AF091317.1


(A/swine/Netherlands/12/85(H1N1)) segment 4
linear mRNA
GI: 4585176


hemagglutinin precursor (HA) mRNA, complete




cds




Influenza A virus
539 bp
X75791.1


(A/swine/Netherlands/25/1980(H1N1)) mRNA for
linear mRNA
GI: 438105


nucleoprotein




Influenza A virus
981 bp
U46942.1


(A/swine/Netherlands/3/1980(H1N1))
linear mRNA
GI: 1912334


hemagglutinin (HA) mRNA, partial cds




Influenza A virus
1,778 bp
AF091314.1


(A/swine/Netherlands/3/80(H1N1)) segment 4
linear mRNA
GI: 4585170


hemagglutinin precursor (HA) mRNA, complete




cds




Influenza A virus (A/NJ/11/76 (H1N1))
1,410 bp
AF250363.2


neuraminidase (NA) gene, complete cds
linear mRNA
GI: 13260583


Influenza A virus (A/Swine/Quebec/192/81
1,438 bp
U86144.1


(SwQc81)) neuraminidase mRNA, complete cds
linear mRNA
GI: 4099318


Influenza A virus (A/Swine/Quebec/5393/91
1,438 bp
U86145.1


(SwQc91)) neuraminidase mRNA, complete cds
linear mRNA
GI: 4099320


Influenza A virus (A/swine/Schleswig-
1,730 bp
Z46435.1


Holstein/1/1992(H1N1)) mRNA for hemagglutinin
linear mRNA
GI: 854216


precursor




Influenza A Virus (A/swine/Schleswig-
1,554 bp
Z46438.1


Holstein/1/1993(H1N1)) mRNA for nucleoprotein
linear mRNA
GI: 854222


Influenza A virus
1,778 bp
AF091307.1


(A/swine/Wisconsin/1/61(H1N1)) segment 4
linear mRNA
GI: 4585156


hemagglutinin precursor (HA) mRNA, complete




cds




212. Influenza A virus
1,565 bp
M76607.1


(A/swine/Wisconsin/1/1967(H1N1))
linear mRNA
GI: 325086


nucleoprotein mRNA, complete cds




Influenza A virus
1,565 bp
M76608.1


(A/swine/Wisconsin/1915/1988(H1N1))
linear mRNA
GI: 325088


nucleoprotein mRNA, complete cds




Influenza A virus
1,550 bp
L46850.1


(A/swine/WI/1915/1988(H1N1)) nucleoprotein
linear mRNA
GI: 954757


(segment 5) mRNA, complete cds




Influenza A virus
729 bp
AJ532568.1


(A/Switzerland/8808/2002(H1N1)) partial m1
linear mRNA
GI: 31096461


gene for matrix protein 1 and partial m2 gene




for matrix protein 2, genomic RNA




Influenza A virus
561 bp
AF362803.1


(A/human/Taiwan/0012/00(H1N1)) hemagglutinin
linear mRNA
GI: 14571975


(HA) mRNA, partial cds




Influenza A virus
561 bp
AF362779.1


(A/human/Taiwan/0016/00(H1N1)) hemagglutinin
linear mRNA
GI: 14571927


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/0016/2000 (H1N1))
303 bp
AY303752.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330993


partial cds




Influenza A virus
561 bp
AF362780.1


(A/human/Taiwan/0030/00(H1N1)) hemagglutinin
linear mRNA
GI: 14571929


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/0030/2000 (H1N1))
303 bp
AY303704.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330897


partial cds




Influenza A virus (A/Taiwan/0032/2002(H1N1))
494 bp
AY604804.1


hemagglutinin mRNA, partial cds
linear mRNA
GI: 50727488


Influenza A virus (A/Taiwan/0061/2002(H1N1))
494 bp
AY604795.1


hemagglutinin mRNA, partial cds
linear mRNA
GI: 50727470


Influenza A virus (A/Taiwan/0069/2002(H1N1))
494 bp
AY604803.1


hemagglutinin mRNA, partial cds
linear mRNA
GI: 50727486


Influenza A virus (A/Taiwan/0078/2002(H1N1))
494 bp
AY604805.1


hemagglutinin mRNA, partial cds
linear mRNA
GI: 50727490


Influenza A virus (A/Taiwan/0094/2002(H1N1))
494 bp
AY604797.1


hemagglutinin mRNA, partial cds
linear mRNA
GI: 50727474


Influenza A virus (A/Taiwan/0116/2002(H1N1))
494 bp
AY604796.1


hemagglutinin mRNA, partial cds
linear mRNA
GI: 50727472


Influenza A virus
564 bp
AF362781.1


(A/human/Taiwan/0130/96(H1N1)) hemagglutinin
linear mRNA
GI: 14571931


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/0130/96 (H1N1))
303 bp
AY303707.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330903


partial cds




Influenza A virus
564 bp
AF362782.1


(A/human/Taiwan/0132/96(H1N1)) hemagglutinin
linear mRNA
GI: 14571933


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/0132/96 (H1N1))
303 bp
AY303708.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330905


partial cds




Influenza A virus
564 bp
AF362783.1


(A/human/Taiwan/0211/96(H1N1)) hemagglutinin
linear mRNA
GI: 14571935


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/0211/96 (H1N1))
303 bp
AY303709.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330907


partial cds




Influenza A virus
564 bp
AF362784.1


(A/human/Taiwan/0235/96(H1N1)) hemagglutinin
linear mRNA
GI: 14571937


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/0235/96 (H1N1))
303 bp
AY303710.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330909


partial cds




Influenza A virus
564 bp
AF362785.1


(A/human/Taiwan/0255/96(H1N1)) hemagglutinin
linear mRNA
GI: 14571939


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/0255/96 (H1N1))
303 bp
AY303711.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330911


partial cds




Influenza A virus
564 bp
AF362786.1


(A/human/Taiwan/0337/96(H1N1)) hemagglutinin
linear mRNA
GI: 14571941


(HA) mRNA, partial cds




Influenza A virus
564 bp
AF362787.1


(A/human/Taiwan/0342/96(H1N1)) hemagglutinin
linear mRNA
GI: 14571943


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/0342/96 (H1N1))
303 bp
AY303714.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330917


partial cds




Influenza A virus
561 bp
AF362788.1


(A/human/Taiwan/0464/99(H1N1)) hemagglutinin
linear mRNA
GI: 14571945


(HA) mRNA, partial cds




Influenza A virus
564 bp
AF362789.1


(A/human/Taiwan/0562/95(H1N1)) hemagglutinin
linear mRNA
GI: 14571947


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/0562/95 (H1N1))
303 bp
AY303720.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330929


partial cds




Influenza A virus
564 bp
AF362790.1


(A/human/Taiwan/0563/95(H1N1)) hemagglutinin
linear mRNA
GI: 14571949


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/0563/95 (H1N1))
303 bp
AY303721.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330931


partial cds




Influenza A virus
564 bp
AF362791.1


(A/human/Taiwan/0657/95(H1N1)) hemagglutinin
linear mRNA
GI: 14571951


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/0657/95 (H1N1))
303 bp
AY303724.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330937


partial cds




Influenza A virus (A/Taiwan/0859/2002(H1N1))
494 bp
AY604801.1


hemagglutinin mRNA, partial cds
linear mRNA
GI: 50727482


Influenza A virus
561 bp
AF362792.1


(A/human/Taiwan/0892/99(H1N1)) hemagglutinin
linear mRNA
GI: 14571953


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/0983/2002(H1N1))
494 bp
AY604800.1


hemagglutinin mRNA, partial cds
linear mRNA
GI: 50727480


Influenza A virus (A/Taiwan/1007/2006(H1N1))
507 bp
EU068163.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 158452199


Influenza A virus (A/Taiwan/1015/2006(H1N1))
507 bp
EU068171.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 158452215


Influenza A virus (A/Taiwan/112/1996-1(H1N1))
1,176 bp
AF026153.1


haemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 2554950


Influenza A virus (A/Taiwan/112/1996-2(H1N1))
1,176 bp
AF026154.1


haemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 2554952


Influenza A virus (A/Taiwan/117/1996-1(H1N1))
1,176 bp
AF026155.1


haemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 2554954


Influenza A virus (A/Taiwan/117/1996-2(H1N1))
1,176 bp
AF026156.1


haemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 2554956


Influenza A virus (A/Taiwan/117/1996-3(H1N1))
1,176 bp
AF026157.1


haemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 2554958


Influenza A virus (A/Taiwan/118/1996-1(H1N1))
1,176 bp
AF026158.1


haemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 2554960


Influenza A virus (A/Taiwan/118/1996-2(H1N1))
1,176 bp
AF026159.1


haemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 2554962


Influenza A virus (A/Taiwan/118/1996-3(H1N1))
1,176 bp
AF026160.1


haemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 2554964


Influenza A virus
561 bp
AF362793.1


(A/human/Taiwan/1184/99(HIN1)) hemagglutinin
linear mRNA
GI: 14571955


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/1184/99 (H1N1))
303 bp
AY303726.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330941


partial cds




Influenza A virus
564 bp
AF362794.1


(A/human/Taiwan/1190/95(H1N1)) hemagglutinin
linear mRNA
GI: 14571957


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/1190/95 (H1N1))
303 bp
AY303727.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330943


partial cds




Influenza A virus (A/Taiwan/1523/2003(H1N1))
494 bp
AY604808.1


hemagglutinin mRNA, partial cds
linear mRNA
GI: 50727496


Influenza A virus (A/Taiwan/1566/2003(H1N1))
494 bp
AY604806.1


hemagglutinin mRNA, partial cds
linear mRNA
GI: 50727492


Influenza A virus (A/Taiwan/1769/96(H1N1))
875 bp
AF138710.2


matrix protein M1 (M) mRNA, partial cds
linear mRNA
GI: 4996871


Influenza A virus (A/Taiwan/1906/2002(H1N1))
494 bp
AY604799.1


hemagglutinin mRNA, partial cds
linear mRNA
GI: 50727478


Influenza A virus (A/Taiwan/1922/2002(H1N1))
494 bp
AY604802.1


hemagglutinin mRNA, partial cds
linear mRNA
GI: 50727484


Influenza A virus (A/Taiwan/2069/2006(H1N1))
507 bp
EU068168.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 158452209


Influenza A virus (A/Taiwan/2157/2001 (H1N1))
303 bp
AY303733.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330955


partial cds




Influenza A virus (A/Taiwan/2175/2001 (H1N1))
561 bp
AY303734.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32330957


Influenza A virus
564 bp
AF362795.1


(A/human/Taiwan/2200/95(H1N1)) hemagglutinin
linear mRNA
GI: 14571959


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/2200/95 (H1N1))
303 bp
AY303737.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330963


partial cds




Influenza A virus (A/Taiwan/2966/2006(H1N1))
507 bp
EU068170.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 158452213


Influenza A virus (A/Taiwan/3168/2005(H1N1))
507 bp
EU068174.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 158452221


Influenza A virus
561 bp
AF362796.1


(A/human/Taiwan/3355/97(H1N1)) hemagglutinin
linear mRNA
GI: 14571961


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/3355/97 (H1N1))
303 bp
AY303739.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330967


partial cds




Influenza A virus (A/Taiwan/3361/2001 (H1N1))
303 bp
AY303740.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330969


partial cds




Influenza A virus (A/Taiwan/3361/2001 (H1N1))
561 bp
AY303741.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32330971


Influenza A virus (A/Taiwan/3518/2006(H1N1))
507 bp
EU068169.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 158452211


Influenza A virus
581 bp
AF362797.1


(A/human/Taiwan/3825/00(H1N1)) hemagglutinin
linear mRNA
GI: 14571963


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/3896/2001 (H1N1))
303 bp
AY303746.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330981


partial cds




Influenza A virus (A/Taiwan/3896/2001 (H1N1))
561 bp
AY303747.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32330983


Influenza A virus (A/Taiwan/4050/2003(H1N1))
494 bp
AY604807.1


hemagglutinin mRNA, partial cds
linear mRNA
GI: 50727494


Influenza A virus (A/Taiwan/4054/2006(H1N1))
507 bp
EU068160.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 158452193


Influenza A virus
561 bp
AF362798.1


(A/human/Taiwan/4360/99(H1N1)) hemagglutinin
linear mRNA
GI: 14571965


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/4360/99 (H1N1))
303 bp
AY303748.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330985


partial cds




Influenza A virus
561 bp
AF362799.1


(A/human/Taiwan/4415/99(H1N1)) hemagglutinin
linear mRNA
GI: 14571967


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/4415/99 (H1N1))
303 bp
AY303749.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330987


partial cds




Influenza A virus (A/Taiwan/4509/2006(H1N1))
507 bp
EU068165.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 158452203


Influenza A virus
561 bp
AF362800.1


(A/human/Taiwan/4845/99(H1N1)) hemagglutinin
linear mRNA
GI: 14571969


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/4845/99 (H1N1))
303 bp
AY303750.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330989


partial cds




Influenza A virus
561 bp
AF362801.1


(A/human/Taiwan/4943/99(H1N1)) hemagglutinin
linear mRNA
GI: 14571971


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/5010/2006(H1N1))
507 bp
EU068167.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 158452207


Influenza A virus
561 bp
AF362802.1


(A/human/Taiwan/5063/99(H1N1)) hemagglutinin
linear mRNA
GI: 14571973


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/5063/99 (H1N1))
303 bp
AY303751.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330991


partial cds




Influenza A virus (A/Taiwan/5084/2006(H1N1))
507 bp
EU068166.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 158452205


Influenza A virus (A/Taiwan/511/96(H1N1))
875 bp
AF138708.2


matrix protein M1 (M) mRNA, partial cds
linear mRNA
GI: 4996867


Influenza A virus (A/Taiwan/557/2006(H1N1))
507 bp
EU068156.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 158452185


Influenza A virus (A/Taiwan/562/2006(H1N1))
507 bp
EU068159.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 158452191


Influenza A virus
561 bp
AF362778.1


(A/human/Taiwan/5779/98(H1N1)) hemagglutinin
linear mRNA
GI: 14571925


(HA) mRNA, partial cds




Influenza A virus (A/Taiwan/5779/98 (H1N1))
303 bp
AY303702.1


polymerase basic protein 1 (PB1) mRNA,
linear mRNA
GI: 32330893


partial cds




Influenza A virus (A/Taiwan/6025/2005(H1N1))
507 bp
EU068172.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 158452217


Influenza A virus (A/Taiwan/607/2006(H1N1))
507 bp
EU068157.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 158452187


Influenza A virus (A/Taiwan/615/2006(H1N1))
507 bp
EU068162.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 158452197


Influenza A virus (A/Taiwan/645/2006(H1N1))
507 bp
EU068164.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 158452201


Influenza A virus (A/Taiwan/680/2005(H1N1))
507 bp
EU068173.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 158452219


Influenza A virus (A/Taiwan/719/2006(H1N1))
507 bp
EU068158.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 158452189


Influenza A virus
1,410 bp
EU021285.1


(A/Thailand/CU124/2006(H3N2)) neuraminidase
linear mRNA
GI: 154224724


(NA) mRNA, complete cds




Influenza A virus
1,413 bp
EU021265.1


(A/Thailand/CU32/2006(H1N1)) neuraminidase
linear mRNA
GI: 154224704


(NA) mRNA, complete cds




Influenza A virus
1,698 bp
EU021264.1


(A/Thailand/CU32/2006(H1N1)) hemagglutinin
linear mRNA
GI: 154224775


(HA) mRNA, complete cds




Influenza A virus
1,413 bp
EU021247.1


(A/Thailand/CU41/2006(H1N1)) neuraminidase
linear mRNA
GI: 154224686


(NA) mRNA, complete cds




Influenza A virus
1,698 bp
EU021246.1


(A/Thailand/CU41/2006(H1N1)) hemagglutinin
linear mRNA
GI: 154224757


(HA) mRNA, complete cds




Influenza A virus
1,413 bp
EU021259.1


(A/Thailand/CU44/2006(H1N1)) neuraminidase
linear mRNA
GI: 154224698


(NA) mRNA, complete cds




Influenza A virus
1,698 bp
EU021258.1


(A/Thailand/CU44/2006(H1N1)) hemagglutinin
linear mRNA
GI: 154224769


(HA) mRNA, complete cds




Influenza A virus
1,413 bp
EU021255.1


(A/Thailand/CU51/2006(H1N1)) neuraminidase
linear mRNA
GI: 154224694


(NA) mRNA, complete cds




Influenza A virus
1,698 bp
EU021254.1


(A/Thailand/CU51/2006(H1N1)) hemagglutinin
linear mRNA
GI: 154224765


(HA) mRNA, complete cds




Influenza A virus
1,413 bp
EU021249.1


(A/Thailand/CU53/2006(H1N1)) neuraminidase
linear mRNA
GI: 154224688


(NA) mRNA, complete cds




Influenza A virus
1,698 bp
EU021248.1


(A/Thailand/CU53/2006(H1N1)) hemagglutinin
linear mRNA
GI: 154224759


(HA) mRNA, complete cds




Influenza A virus
1,413 bp
EU021257.1


(A/Thailand/CU57/2006(H1N1)) neuraminidase
linear mRNA
GI: 154224696


(NA) mRNA, complete cds




Influenza A virus
1,698 bp
EU021256.1


(A/Thailand/CU57/2006(H1N1)) hemagglutinin
linear mRNA
GI: 154224767


(HA) mRNA, complete cds




Influenza A virus
1,413 bp
EU021251.1


(A/Thailand/CU67/2006(H1N1)) neuraminidase
linear mRNA
GI: 154224690


(NA) mRNA, complete cds




Influenza A virus
1,698 bp
EU021250.1


(A/Thailand/CU67/2006(H1N1)) hemagglutinin
linear mRNA
GI: 154224761


(HA) mRNA, complete cds




Influenza A virus
1,413 bp
EU021261.1


(A/Thailand/CU68/2006(H1N1)) neuraminidase
linear mRNA
GI: 154224700


(NA) mRNA, complete cds




Influenza A virus
1,698 bp
EU021260.1


(A/Thailand/CU68/2006(H1N1)) hemagglutinin
linear mRNA
GI: 154224771


(HA) mRNA, complete cds




Influenza A virus
1,413 bp
EU021263.1


(A/Thailand/CU75/2006(H1N1)) neuraminidase
linear mRNA
GI: 154224702


(NA) mRNA, complete cds




Influenza A virus
1,698 bp
EU021262.1


(A/Thailand/CU75/2006(H1N1)) hemagglutinin
linear mRNA
GI: 154224773


(HA) mRNA, complete cds




Influenza A virus
1,413 bp
EU021253.1


(A/Thailand/CU88/2006(H1N1)) neuraminidase
linear mRNA
GI: 154224692


(NA) mRNA, complete cds




Influenza A virus
1,698 bp
EU021252.1


(A/Thailand/CU88/2006(H1N1)) hemagglutinin
linear mRNA
GI: 154224763


(HA) mRNA, complete cds




Influenza A virus
1,565 bp
M76603.1


(A/turkey/England/647/1977(H1N1))
linear mRNA
GI: 325094


nucleoprotein mRNA, complete cds




Influenza A virus
1,445 bp
AJ416626.1


(A/turkey/France/87075/87(H1N1)) N1 gene for
linear mRNA
GI: 39840719


neuraminidase, genomic RNA




Influenza A virus
394 bp
Z30272.1


(A/turkey/Germany/3/91(H1N1)) mRNA for PB2
linear mRNA
GI: 456652


polymerase (partial)




Influenza A virus
97 bp
Z30275.1


(A/turkey/Germany/3/91(H1N1)) mRNA for
linear mRNA
GI: 530398


neuraminidase (UTR)




Influenza A virus
264 bp
Z30274.1


(A/turkey/Germany/3/91(H1N1)) mRNA for PA
linear mRNA
GI: 530401


polymerase




Influenza A virus
247 bp
Z30273.1


(A/turkey/Germany/3/91(H1N1)) mRNA for PBI
linear mRNA
GI: 530403


polymerase (partial)




Influenza A virus
1,038 bp
Z46441.1


(A/turkey/Germany/3/91(H1N1)) mRNA for
linear mRNA
GI: 854218


hemagglutinin HA1




Influenza A virus
981 bp
U46941.1


(A/turkey/Minnesota/1661/1981(H1N1))
linear mRNA
GI: 1912332


hemagglutinin (HA) mRNA, partial cds




Influenza A virus
1,777 bp
AF091310.1


(A/turkey/Minnesota/1661/81(H1N1)) segment 4
linear mRNA
GI: 4585162


hemagglutinin precursor (HA) mRNA, complete




cds




Influenza A virus (A/turkey/North
1,565 bp
M7 6609.1


Carolina/1790/1988(H1N1)) nucleoprotein mRNA,
linear mRNA
GI: 325096


complete cds




Influenza A virus (A/Weiss/43 (H1N1))
1,410 bp
AF250365.2


neuraminidase (NA) gene, complete cds
linear mRNA
GI: 13260589


Influenza A virus (A/Wilson-Smith/1933(H1N1))
1,497 bp
EU330203.1


nucleocapsid protein (NP) mRNA, complete cds
linear mRNA
GI: 167989512


Influenza A virus
241 bp
U47816.1


(A/Wisconsin/3523/1988(H1N1)) neuraminidase
linear mRNA
GI: 1912352


(NA) mRNA, partial cds




Influenza A virus
1,565 bp
M7 6610.1


(A/Wisconsin/3623/1988(H1N1)) nucleoprotein
linear mRNA
GI: 325103


mRNA, complete cds




Influenza A virus (A/WI/4754/1994(H1N1)) PB1
235 bp
U53156.1


(PB1) mRNA, partial cds
linear mRNA
GI: 1399590


Influenza A virus (A/WI/4754/1994(H1N1)) PB2
168 bp
U53158.1


(PB2) mRNA, partial cds
linear mRNA
GI: 1399594


Influenza A virus (A/WI/4754/1994(H1N1)) PA
621 bp
U53160.1


(PA) mRNA, partial cds
linear mRNA
GI: 1399598


Influenza A virus (A/WI/4754/1994(H1N1))
1,778 bp
U53162.1


hemagglutinin (HA) mRNA, complete cds
linear mRNA
GI: 1399602


Influenza A virus (A/WI/4754/1994(H1N1)) NP
200 bp
U53164.1


(NP) mRNA, partial cds
linear mRNA
GI: 1399606


Influenza A virus (A/WI/4754/1994(H1N1))
1,458 bp
U53166.1


neuraminidase (NA) mRNA, complete cds
linear mRNA
GI: 1399610


Influenza A virus (A/WI/4754/1994(H1N1)) M
1,027 bp
U53168.1


(M) mRNA, complete cds
linear mRNA
GI: 1399614


Influenza A virus (A/WI/4754/1994(H1N1)) NS
890 bp
U53170.1


(NS) mRNA, complete cds
linear mRNA
GI: 1399618


Influenza A virus (A/WI/4755/1994(H1N1)) PB1
203 bp
U53157.1


(PB1) mRNA, partial cds
linear mRNA
GI: 1399592


Influenza A virus (A/WI/4755/1994(H1N1)) PB2
173 bp
U53159.1


(PB2) mRNA, partial cds
linear mRNA
GI: 1399596


Influenza A virus (A/WI/4755/1994(H1N1)) PA
621 bp
U53161.1


(PA) mRNA, partial cds
linear mRNA
GI: 1399600


Influenza A virus (A/WI/4755/1994(H1N1))
1,778 bp
U53163.1


hemagglutinin (HA) mRNA, complete cds
linear mRNA
GI: 1399604


Influenza A virus (A/WI/4755/1994(H1N1)) NP
215 bp
U53165.1


(NP) mRNA, partial cds
linear mRNA
GI: 1399608


Influenza A virus (A/WI/4755/1994(H1N1))
209 bp
U53167.1


neuraminidase (NA) mRNA, partial cds
linear mRNA
GI: 1399612


Influenza A virus (A/WI/4755/1994(H1N1)) M
1,027 bp
U53169.1


(M) mRNA, complete cds
linear mRNA
GI: 1399616


Influenza A virus (A/WI/4755/1994(H1N1)) NS
890 bp
U53171.1


(NS) mRNA, complete cds
linear mRNA
GI: 1399620


Influenza A virus (A/WSN/33) segment 5
543 bp
AF306656.1


nucleocapsid protein (NP) mRNA, partial cds
linear mRNA
GI: 11935089
















TABLE 8







Influenza H3N2 Antigens











GenBank/GI


Strain/Protein
Length
Accession No.





 1. Influenza A virus (A/Aichi/2/1968(H3N2))
1,704 bp
EF614248.1


hemagglutinin (HA) mRNA, complete cds
linear mRNA
GI: 148910819


 2. Influenza A virus (A/Aichi/2/1968(H3N2))
1,698 bp
EF614249.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 148910821


 3. Influenza A virus (A/Aichi/2/1968(H3N2))
1,698 bp
EF614250.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 148910823


 4. Influenza A virus (A/Aichi/2/1968(H3N2))
1,698 bp
EF614251.1


hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 148910825


 5. Influenza A virus (A/Akita/1/1995(H3N2))
1,032 bp
U48444.1


haemagglutinin mRNA, partial cds
linear mRNA
GI: 1574989


 6. Influenza A virus
1,041 bp
Z46392.1


(A/Beijing/32/1992(H3N2)) mRNA for
linear mRNA
GI: 609020


haemagglutinin




 7. Influenza A virus
987 bp
AF501516.1


(A/Canada/33312/99(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 21314288


mRNA, partial cds




 8. Influenza A virus
987 bp
AF297094.1


(A/Charlottesville/10/99 (H3N2))
linear mRNA
GI: 11228917


hemagglutinin mRNA, partial cds




 9. Influenza A virus
987 bp
AF297096.1


(A/Charlottesville/49/99 (H3N2))
linear mRNA
GI: 11228921


hemagglutinin mRNA, partial cds




 10. Influenza A virus
987 bp
AF297097.1


(A/Charlottesville/69/99 (H3N2))
linear mRNA
GI: 11228923


hemagglutinin mRNA, partial cds




 11. Influenza A virus
987 bp
AF297095.1


(A/Charlottesville/73/99 (H3N2))
linear mRNA
GI: 11228919


hemagglutinin mRNA, partial cds




 12. Influenza A virus
1,041 bp
Z46393.1


(A/England/1/1993(H3N2)) mRNA for
linear mRNA
GI: 609024


haemagglutinin




 13. Influenza A virus
1,041 bp
Z46394.1


(A/England/247/1993(H3N2)) mRNA for
linear mRNA
GI: 609025


haemagglutinin




 14. Influenza A virus
1,041 bp
Z46395.1


(A/England/269/93(H3N2)) mRNA for
linear mRNA
GI: 609027


haemagglutinin




 15. Influenza A virus
1,041 bp
Z46396.1


(A/England/284/1993(H3N2)) mRNA for
linear mRNA
GI: 609029


haemagglutinin




 16. Influenza A virus
1,041 bp
Z46397.1


(A/England/286/1993(H3N2)) mRNA for
linear mRNA
GI: 609031


haemagglutinin




 17. Influenza A virus
1,041 bp
Z46398.1


(A/England/289/1993(H3N2)) mRNA for
linear mRNA
GI: 609033


haemagglutinin




 18. Influenza A virus
1,041 bp
Z46399.1


(A/England/328/1993(H3N2)) mRNA for
linear mRNA
GI: 609035


haemagglutinin




 19. Influenza A virus
1,041 bp
Z46400.1


(A/England/346/1993(H3N2)) mRNA for
linear mRNA
GI: 609037


haemagglutinin




 20. Influenza A virus
1,041 bp
Z46401.1


(A/England/347/1993(H3N2)) mRNA for
linear mRNA
GI: 609039


haemagglutinin




 21. Influenza A virus
1,091 bp
AF201875.1


(A/England/42/72(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 6470274


partial cds




 22. Influenza A virus
1,041 bp
Z46402.1


(A/England/471/1993(H3N2)) mRNA for
linear mRNA
GI: 609041


haemagglutinin




 23. Influenza A virus
1,041 bp
Z46403.1


(A/England/67/1994(H3N2)) mRNA for
linear mRNA
GI: 609043


haemagglutinin




 24. Influenza A virus
1,041 bp
Z46404.1


(A/England/68/1994(H3N2)) mRNA for
linear mRNA
GI: 609045


haemagglutinin




 25. Influenza A virus
1,041 bp
Z46405.1


(A/England/7/1994(H3N2)) mRNA for
linear mRNA
GI: 609047


haemagglutinin




 28. Influenza A virus
1,041 bp
Z46406.1


(A/Guangdong/25/1993(H3N2)) mRNA for
linear mRNA
GI: 609049


haemagglutinin




 29. Influenza A virus (A/Hong
1,091 bp
AF201874.1


Kong/1/68(H3N2)) hemagglutinin mRNA, partial
linear mRNA
GI: 6470272


cds




 30. Influenza A virus (A/Hong
1,041 bp
Z46407.1


Kong/1/1994(H3N2)) mRNA for haemagglutinin
linear mRNA
GI: 609051


 31. Influenza A virus (A/Hong
1,762 bp
AF382319.1


Kong/1143/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14487957


complete cds




 32. Influenza A virus (A/Hong
1,762 bp
AF382320.1


Kong/1143/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14487959


complete cds




 33. Influenza A virus (A/Hong
1,466 bp
AF382329.1


Kong/1143/99(H3N2)) neuraminidase mRNA,
linear mRNA
GI: 14487977


complete cds




 34. Influenza A virus (A/Hong
1,466 bp
AF382330.1


Kong/1143/99(H3N2)) neuraminidase mRNA,
linear mRNA
GI: 14487979


complete cds




 35. Influenza A virus (A/Hong
1,762 bp
AY035589.1


Kong/1144/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14486403


complete cds




 36. Influenza A virus (A/Hong
1,762 bp
AF382321.1


Kong/1144/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14487961


complete cds




 37. Influenza A virus (A/Hong
1,762 bp
AF382322.1


Kong/1144/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14487963


complete cds




 38. Influenza A virus (A/Hong
1,466 bp
AF382331.1


Kong/1144/99(H3N2)) neuraminidase mRNA,
linear mRNA
GI: 14487981


complete cds




 39. Influenza A virus (A/Hong
1,466 bp
AF382332.1


Kong/1144/99(H3N2)) neuraminidase mRNA,
linear mRNA
GI: 14487983


complete cds




 40. Influenza A virus (A/Hong
1,762 bp
AY035590.1


Kong/1179/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14486405


complete cds




 41. Influenza A virus (A/Hong
1,762 bp
AF382323.1


Kong/1179/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14487965


complete cds




 42. Influenza A virus (A/Hong
1,762 bp
AF382324.1


Kong/1179/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14487967


complete cds




 43. Influenza A virus (A/Hong
1,762 bp
AY035591.1


Kong/1180/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14486407


complete cds




 44. Influenza A virus (A/Hong
1,762 bp
AF382325.1


Kong/1180/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14487969


complete cds




 45. Influenza A virus (A/Hong
1,762 bp
AF382326.1


Kong/1180/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14487971


complete cds




 46. Influenza A virus (A/Hong
1,762 bp
AF382327.1


Kong/1182/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14487973


complete cds




 47. Influenza A virus (A/Hong
1,762 bp
AF382328.1


Kong/1182/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14487975


complete cds




 48. Influenza A virus (A/Hong
1,041 bp
Z46408.1


Kong/2/1994(H3N2)) mRNA for haemagglutinin
linear mRNA
GI: 609055


 49. Influenza A virus (A/Hong
1,041 bp
Z46410.1


Kong/23/1992(H3N2)) mRNA for haemagglutinin
linear mRNA
GI: 609053


 50. Influenza A virus (A/Hong
1,041 bp
Z46409.1


Kong/34/1990(H3N2)) mRNA for haemagglutinin
linear mRNA
GI: 609057


 51. Influenza A virus
1,041 bp
Z46397.1


(A/England/286/1993(H3N2)) mRNA for
linear mRNA
GI: 609031


haemagglutinin




 52. Influenza A virus
1,041 bp
Z46398.1


(A/England/289/1993(H3N2)) mRNA for
linear mRNA
GI: 609033


haemagglutinin




 53. Influenza A virus
1,041 bp
Z46399.1


(A/England/328/1993(H3N2)) mRNA for
linear mRNA
GI: 609035


haemagglutinin




 54. Influenza A virus
1,041 bp
Z46400.1


(A/England/346/1993(H3N2)) mRNA for
linear mRNA
GI: 609037


haemagglutinin




 55. Influenza A virus
1,041 bp
Z46401.1


(A/England/347/1993(H3N2)) mRNA for
linear mRNA
GI: 609039


haemagglutinin




 56. Influenza A virus
1,091 bp
AF201875.1


(A/England/42/72(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 6470274


partial cds




 57. Influenza A virus
1,041 bp
Z46402.1


(A/England/471/1993(H3N2)) mRNA for
linear mRNA
GI: 609041


haemagglutinin




 58. Influenza A virus
1,041 bp
Z46403.1


(A/England/67/1994(H3N2)) mRNA for
linear mRNA
GI: 609043


haemagglutinin




 59. Influenza A virus
1,041 bp
Z46404.1


(A/England/68/1994(H3N2)) mRNA for
linear mRNA
GI: 609045


haemagglutinin




 60. Influenza A virus
1,041 bp
Z46405.1


(A/England/7/1994(H3N2)) mRNA for
linear mRNA
GI: 609047


haemagglutinin




 63. Influenza A virus
1,032 bp
U48442.1


(A/Guandong/28/1994(H3N2)) haemagglutinin
linear mRNA
GI: 1574985


mRNA, partial cds




 64. Influenza A virus
1,041 bp
Z46406.1


(A/Guangdong/25/1993(H3N2)) mRNA for
linear mRNA
GI: 609049


haemagglutinin




 65. Influenza A virus
1,032 bp
U48447.1


(A/Hebei/19/1995(H3N2)) haemagglutinin mRNA,
linear mRNA
GI: 1574995


partial cds




 66. Influenza A virus
1,032 bp
U48441.1


(A/Hebei/41/1994(H3N2)) haemagglutinin mRNA,
linear mRNA
GI: 1574983


partial cds




 67. Influenza A virus (A/Hong
1,091 bp
AF201874.1


Kong/1/68(H3N2)) hemagglutinin mRNA, partial
linear mRNA
GI: 6470272


cds




 68. Influenza A virus (A/Hong
1,041 bp
Z46407.1


Kong/1/1994(H3N2)) mRNA for haemagglutinin
linear mRNA
GI: 609051


 69. Influenza A virus (A/Hong
1,762 bp
AY035588.1


Kong/1143/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14486401


complete cds




 70. Influenza A virus (A/Hong
1,762 bp
AF382319.1


Kong/1143/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14487957


complete cds




 71. Influenza A virus (A/Hong
1,762 bp
AF382320.1


Kong/1143/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14487959


complete cds




 72. Influenza A virus (A/Hong
1,466 bp
AF382329.1


Kong/1143/99(H3N2)) neuraminidase mRNA,
linear mRNA
GI: 14487977


complete cds




 73. Influenza A virus (A/Hong
1,466 bp
AF382330.1


Kong/1143/99(H3N2)) neuraminidase mRNA,
linear mRNA
GI: 14487979


complete cds




 74. Influenza A virus (A/Hong
1,762 bp
AY035589.1


Kong/1144/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14486403


complete cds




 75. Influenza A virus (A/Hong
1,762 bp
AF382321.1


Kong/1144/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14487961


complete cds




 76. Influenza A virus (A/Hong
1,762 bp
AF382322.1


Kong/1144/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14487963


complete cds




 77. Influenza A virus (A/Hong
1,466 bp
AF382331.1


Kong/1144/99(H3N2)) neuraminidase mRNA,
linear mRNA
GI: 14487981


complete cds




 78. Influenza A virus (A/Hong
1,466 bp
AF382332.1


Kong/1144/99(H3N2)) neuraminidase mRNA,
linear mRNA
GI: 14487983


complete cds




 79. Influenza A virus (A/Hong
1,762 bp
AY035590.1


Kong/1179/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14486405


complete cds




 80. Influenza A virus (A/Hong
1,762 bp
AF382323.1


Kong/1179/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14487965


complete cds




 81. Influenza A virus (A/Hong
1,762 bp
AF382324.1


Kong/1179/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14487967


complete cds




 82. Influenza A virus (A/Hong
1,762 bp
AY035591.1


Kong/1180/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14486407


complete cds




 83. Influenza A virus (A/Hong
1,762 bp
AF382325.1


Kong/1180/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14487969


complete cds




 84. Influenza A virus (A/Hong
1,762 bp
AF382326.1


Kong/1180/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14487971


complete cds




 85. Influenza A virus (A/Hong
1,762 bp
AY035592.1


Kong/1182/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14486409


complete cds




 86. Influenza A virus (A/Hong
1,762 bp
AF382327.1


Kong/1182/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14487973


complete cds




 87. Influenza A virus (A/Hong
1,762 bp
AF382328.1


Kong/1182/99(H3N2)) hemagglutinin mRNA,
linear mRNA
GI: 14487975


complete cds




 88. Influenza A virus (A/Hong
1,041 bp
Z46408.1


Kong/2/1994(H3N2)) mRNA for haemagglutinin
linear mRNA
GI: 609055


 89. Influenza A virus (A/Hong
1,041 bp
Z46410.1


Kong/23/1992(H3N2)) mRNA for haemagglutinin
linear mRNA
GI: 609053


 90. Influenza A virus (A/Hong
1,041 bp
Z46409.1


Kong/34/1990(H3N2)) mRNA for haemagglutinin
linear mRNA
GI: 609057


 91. Influenza A virus
987 bp
AF501534.1


(A/Indiana/28170/99(H3N2)) hemagglutinin
linear mRNA
GI: 21314324


(HA) mRNA, partial cds




 92. Influenza A virus
529 bp
AY961997.1


(A/Kinmen/618/03(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138151


mRNA, partial cds




 93. Influenza A virus
383 bp
AY973325.1


(A/Kinmen/618/03(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673206


mRNA, partial cds




 94. Influenza A virus
882 bp
AY986986.1


(A/Kinmen/618/03(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728099


mRNA, partial cds




 95. Influenza A virus
545 bp
AY962017.1


(A/Kinmen/621/03(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138191


mRNA, partial cds




 96. Influenza A virus
386 bp
AY973326.1


(A/Kinmen/621/03(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673208


mRNA, partial cds




 97. Influenza A virus
882 bp
AY986987.1


(A/Kinmen/621/03(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728101


mRNA, partial cds




 98. Influenza A virus
786 bp
AY962008.1


(A/Kinmen/639/04(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138173


mRNA, partial cds




 99. Influenza A virus
381 bp
AY973327.1


(A/Kinmen/639/04(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673210


mRNA, partial cds




100. Influenza A virus
882 bp
AY986988.1


(A/Kinmen/639/04(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728103


mRNA, partial cds




101. Influenza A virus
596 bp
AY962004.1


(A/Kinmen/641/04(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138165


mRNA, partial cds




102. Influenza A virus
785 bp
AY973328.1


(A/Kinmen/641/04(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673212


mRNA, partial cds




103. Influenza A virus
576 bp
AY962001.1


(A/Kinmen/642/04(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138159


mRNA, partial cds




104. Influenza A virus
580 bp
AY973329.1


(A/Kinmen/642/04(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673214


mRNA, partial cds




105. Influenza A virus
882 bp
AY986989.1


(A/Kinmen/642/04(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728105


mRNA, partial cds




106. Influenza A virus
789 bp
AY962009.1


(A/Kinmen/645/04(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138175


mRNA, partial cds




107. Influenza A virus
581 bp
AY973330.1


(A/Kinmen/645/04(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673216


mRNA, partial cds




108. Influenza A virus
981 bp
AY986990.1


(A/Kinmen/645/04(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728107


mRNA, partial cds




109. Influenza A virus
2,341 bp
U62543.1


(A/LosAngeles/2/1987(H3N2)) polymerase
linear mRNA
GI: 1480737


protein basic 2 (PB2) mRNA, complete cds




110. Influenza A virus
1,041 bp
Z46411.1


(A/Madrid/252/1993(H3N2)) mRNA for
linear mRNA
GI: 609067


haemagglutinin




111. Influenza A virus
987 bp
AF501531.1


(A/Michigan/22568/99(H3N2)) hemagglutinin
linear mRNA
GI: 21314318


(HA) mRNA, partial cds




112. Influenza A virus
987 bp
AF501518.1


(A/Michigan/22692/99(H3N2)) hemagglutinin
linear mRNA
GI: 21314292


(HA) mRNA, partial cds




113. Influenza A virus
754 bp
AJ519454.1


(A/Moscow/10/99(H3N2)) partial NS1 gene for
linear mRNA
GI: 31096423


non structural protein 1 and partial NS2




gene for non structural protein 2, genomic




RNA




114. Influenza A virus
987 bp
AY138518.1


(A/ningbo/17/2002(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 24895178


mRNA, partial cds




115. Influenza A virus
987 bp
AY138517.1


(A/ningbo/25/2002(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 24895169


mRNA, partial cds




116. Influenza A virus
1,765 bp
V01103.1


(A/NT/60/68/29C(H3N2)) mRNA for
linear mRNA
GI: 60800


haemagglutinin (HA1 and HA2 genes)




117. Influenza A virus
1,701 bp
DQ059385.1


(A/Oklahoma/323/03(H3N2)) hemagglutinin
linear mRNA
GI: 66933143


mRNA, complete cds




118. Influenza A virus
1,410 bp
DQ059384.2


(A/Oklahoma/323/03(H3N2)) neuraminidase
linear mRNA
GI: 75859981


mRNA, complete cds




119. Influenza A virus
766 bp
AJ519458.1


(A/Panama/2007/99(H3N2)) partial NS1 gene
linear mRNA
GI: 31096435


for non structural protein 1 and partial NS2




gene for non structural protein 2, genomic




RNA




120. Influenza A virus
987 bp
AF501526.1


(A/Pennsylvania/20109/99(H3N2))
linear mRNA
GI: 21314308


hemagglutinin (HA) mRNA, partial cds




121. Influenza A virus
1,091 bp
AF233691.1


(A/Philippines/2/82(H3N2)) hemagglutinin
linear mRNA
GI: 7331124


mRNA, partial cds




122. Influenza A virus
767 bp
AY962000.1


(A/Pingtung/303/04(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138157


mRNA, partial cds




123. Influenza A virus
783 bp
AY973331.1


(A/Pingtung/303/04(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673218


mRNA, partial cds




124. Influenza A virus
928 bp
AY986991.1


(A/Pingtung/303/04(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728109


mRNA, partial cds




125. Influenza A virus
788 bp
AY961999.1


(A/Pingtung/313/04(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138155


mRNA, partial cds




126. Influenza A virus
787 bp
AY973332.1


(A/Pingtung/313/04(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673220


mRNA, partial cds




127. Influenza A virus
882 bp
AY986992.1


(A/Pingtung/313/04(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728111


mRNA, partial cds




128. Influenza A virus (A/ruddy
927 bp
AY664458.1


turnstone/Delaware/142/99 (H3N2))
linear mRNA
GI: 51011862


nonfunctional matrix protein mRNA, partial




sequence




129. Influenza A virus
1,041 bp
Z46413.1


(A/Scotland/142/1993(H3N2)) mRNA for
linear mRNA
GI: 609059


haemagglutinin




130. Influenza A virus
1,041 bp
Z46414.1


(A/Scotland/160/1993(H3N2)) mRNA for
linear mRNA
GI: 609061


haemagglutinin




131. Influenza A virus
1,041 bp
Z46416.1


(A/Scotland/173/1993(H3N2)) mRNA for
linear mRNA
GI: 609063


haemagglutinin




132. Influenza A virus
1,041 bp
Z46415.1


(A/Scotland/174/1993(H3N2)) mRNA for
linear mRNA
GI: 609065


haemagglutinin




133. Influenza A virus
1,041 bp
Z46412.1


(A/Scotland/2/1993(H3N2)) mRNA for
linear mRNA
GI: 609069


haemagglutinin




134. Influenza A virus
1,032 bp
U48439.1


(A/Sendai/C182/1994(H3N2)) haemagglutinin
linear mRNA
GI: 1574979


mRNA, partial cds




135. Influenza A virus
1,032 bp
U48445.1


(A/Sendai/c373/1995(H3N2)) haemagglutinin
linear mRNA
GI: 1574991


mRNA, partial cds




136. Influenza A virus
1,032 bp
U48440.1


(A/Sendai/c384/1994(H3N2)) haemagglutinin
linear mRNA
GI: 1574981


mRNA, partial cds




137. Influenza A virus
1,041 bp
Z46417.1


(A/Shangdong/9/1993(H3N2)) mRNA for
linear mRNA
GI: 609071


haemagglutinin




138. Influenza A virus
987 bp
L19416.1


(A/Shanghai/11/1987/X99aE high yield
linear mRNA
GI: 348117


reassortant(H3N2)) hemagglutinin (HA) mRNA,




partial cds




139. Influenza A virus
2,280 bp
AF225514.1


(A/sw/Shizuoka/110/97(H3N2)) polymerase
linear mRNA
GI: 27462098


basic 2 (PB2) mRNA, complete cds




140. Influenza A virus
2,274 bp
AF225518.1


(A/sw/Shizuoka/110/97(H3N2)) polymerase
linear mRNA
GI: 27462106


basic 1 (PB1) mRNA, complete cds




141. Influenza A virus
2,151 bp
AF225522.1


(A/sw/Shizuoka/110/97(H3N2)) polymerase
linear mRNA
GI: 27462114


acidic (PA) mRNA, complete cds




142. Influenza A virus
1,497 bp
AF225534.1


(A/sw/Shizuoka/110/97(H3N2)) nucleoprotein
linear mRNA
GI: 27462146


(NP) mRNA, complete cds




143. Influenza A virus
1,410 bp
AF225538.1


(A/sw/Shizuoka/110/97(H3N2)) neuraminidase
linear mRNA
GI: 27462154


(NA) mRNA, complete cds




144. Influenza A virus
984 bp
AF225542.1


(A/sw/Shizuoka/110/97(H3N2)) hemagglutinin
linear mRNA
GI: 27462162


(HA1) mRNA, partial cds




145. Influenza A virus
2,280 bp
AF225515.1


(A/sw/Shizuoka/115/97(H3N2)) polymerase
linear mRNA
GI: 27462100


basic 2 (PB2) mRNA, complete cds




146. Influenza A virus
2,274 bp
AF225519.1


(A/sw/Shizuoka/115/97(H3N2)) polymerase
linear mRNA
GI: 27462108


basic 1 (PB1) mRNA, complete cds




147. Influenza A virus
2,151 bp
AF225523.1


(A/sw/Shizuoka/115/97(H3N2)) polymerase
linear mRNA
GI: 27462116


acidic (PA) mRNA, complete cds




148. Influenza A virus
1,497 bp
AF225535.1


(A/sw/Shizuoka/115/97(H3N2)) nucleoprotein
linear mRNA
GI: 27462148


(NP) mRNA, complete cds




149. Influenza A virus
1,410 bp
AF225539.1


(A/sw/Shizuoka/115/97(H3N2)) neuraminidase
linear mRNA
GI: 27462156


(NA) mRNA, complete cds




150. Influenza A virus
984 bp
AF225543.1


(A/sw/Shizuoka/115/97(H3N2)) hemagglutinin
linear mRNA
GI: 27462164


(HA1) mRNA, partial cds




151. Influenza A virus
2,280 bp
AF225516.1


(A/sw/Shizuoka/119/97(H3N2)) polymerase
linear mRNA
GI: 27462102


basic 2 (PB2) mRNA, complete cds




152. Influenza A virus
2,274 bp
AF225520.1


(A/sw/Shizuoka/119/97(H3N2)) polymerase
linear mRNA
GI: 27462110


basic 1 (PB1) mRNA, complete cds




153. Influenza A virus
2,151 bp
AF225524.1


(A/sw/Shizuoka/119/97(H3N2)) polymerase
linear mRNA
GI: 27462118


acidic (PA) mRNA, complete cds




154. Influenza A virus
1,497 bp
AF225536.1


(A/sw/Shizuoka/119/97(H3N2)) nucleoprotein
linear mRNA
GI: 27462150


(NP) mRNA, complete cds




155. Influenza A virus
1,410 bp
AF225540.1


(A/sw/Shizuoka/119/97(H3N2)) neuraminidase
linear mRNA
GI: 27462158


(NA) mRNA, complete cds




156. Influenza A virus
984 bp
AF225544.1


(A/sw/Shizuoka/119/97(H3N2)) hemagglutinin
linear mRNA
GI: 27462166


(HA1) mRNA, partial cds




159. Influenza A virus
1,410 bp
EU163948.1


(A/swine/Bakum/1DTI769/2003(H3N2))
linear mRNA
GI: 157679552


neuraminidase mRNA, complete cds




163. Influenza A virus
1,738 bp
AY857957.1


(A/swine/Fujian/668/01(H3N2)) nonfunctional
linear mRNA
GI: 58042507


hemagglutinin mRNA, complete sequence




164. Influenza A virus PB2 gene for
2,280 bp
AJ311459.1


Polymerase 2 protein, genomic RNA, strain
linear mRNA
GI: 13661041


A/Swine/Italy/1523/98




165. Influenza A virus PB1 gene for
2,274 bp
AJ311460.1


Polymerase 1 protein, genomic RNA, strain
linear mRNA
GI: 13661043


A/Swine/Italy/1523/98




166. Influenza A virus
821 bp
AJ344024.1


(A/swine/Italy/1523/98(H3N2)) NS1 gene for
linear mRNA
GI: 20068146


non structural protein 1 and NS2 gene for




non structural protein 2, genomic RNA




167. Influenza A virus
1,465 bp
EU163949.1


(A/swine/Re220/92hp(H3N2)) neuraminidase
linear mRNA
GI: 157679554


mRNA, complete cds




168. Influenza A virus
2,280 bp
AF225517.1


(A/sw/Shizuoka/120/97(H3N2)) polymerase
linear mRNA
GI: 27462104


basic 2 (PB2) mRNA, complete cds




169. Influenza A virus
2,274 bp
AF225521.1


(A/sw/Shizuoka/120/97(H3N2)) polymerase
linear mRNA
GI: 27462112


basic 1 (PB1) mRNA, complete cds




170. Influenza A virus
2,151 bp
AF225525.1


(A/sw/Shizuoka/120/97(H3N2)) polymerase
linear mRNA
GI: 27462120


acidic (PA) mRNA, complete cds




171. Influenza A virus
1,497 bp
AF225537.1


(A/sw/Shizuoka/120/97(H3N2)) nucleoprotein
linear mRNA
GI: 27462152


(NP) mRNA, complete cds




172. Influenza A virus
1,410 bp
AF225541.1


(A/sw/Shizuoka/120/97(H3N2)) neuraminidase
linear mRNA
GI: 27462160


(NA) mRNA, complete cds




173. Influenza A virus
984 bp
AF225545.1


(A/sw/Shizuoka/120/97(H3N2)) hemagglutinin
linear mRNA
GI: 27462168


(HA1) mRNA, partial cds




174. Influenza A virus
1,762 bp
AY032978.1


(A/Switzerland/7729/98(H3N2)) hemagglutinin
linear mRNA
GI: 14161723


mRNA, complete cds




175. Influenza A virus
1,762 bp
AF382318.1


(A/Switzerland/7729/98(H3N2)) hemagglutinin
linear mRNA
GI: 14487955


mRNA, complete cds




176. Influenza A virus
528 bp
AY962011.1


(A/Tainan/704/03(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138179


mRNA, partial cds




177. Influenza A virus
384 bp
AY973333.1


(A/Tainan/704/03(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673222


mRNA, partial cds




178. Influenza A virus
882 bp
AY986993.1


(A/Tainan/704/03(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728113


mRNA, partial cds




179. Influenza A virus
519 bp
AY962012.1


(A/Tainan/712/03(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138181


mRNA, partial cds




180. Influenza A virus
383 bp
AY973334.1


(A/Tainan/712/03(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673224


mRNA, partial cds




181. Influenza A virus
882 bp
AY986994.1


(A/Tainan/712/03(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728115


mRNA, partial cds




182. Influenza A virus
784 bp
AY962005.1


(A/Tainan/722/03(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138167


mRNA, partial cds




183. Influenza A virus
592 bp
AY973335.1


(A/Tainan/722/03(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673226


mRNA, partial cds




184. Influenza A virus
936 bp
AY986995.1


(A/Tainan/722/03(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728117


mRNA, partial cds




185. Influenza A virus
788 bp
AY961998.1


(A/Taipei/407/03(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138153


mRNA, partial cds




186. Influenza A virus
787 bp
AY973336.1


(A/Taipei/407/03(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673228


mRNA, partial cds




187. Influenza A virus
882 bp
AY986996.1


(A/Taipei/407/03(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728119


mRNA, partial cds




188. Influenza A virus
787 bp
AY962007.1


(A/Taipei/416/03(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138171


mRNA, partial cds




189. Influenza A virus
782 bp
AY973337.1


(A/Taipei/416/03(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673230


mRNA, partial cds




190. Influenza A virus
882 bp
AY986997.1


(A/Taipei/416/03(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728121


mRNA, partial cds




191. Influenza A virus (A/Taiwan/0020/98
297 bp
AY303703.1


(H3N2)) polymerase basic protein 1 (PB1)
linear mRNA
GI: 32330895


mRNA, partial cds




192. Influenza A virus
791 bp
AY604817.1


(A/Taiwan/0040/2003(H3N2)) hemagglutinin
linear mRNA
GI: 50727514


mRNA, partial cds




193. Influenza A virus (A/Taiwan/0045/98
297 bp
AY303705.1


(H3N2)) polymerase basic protein 1 (PB1)
linear mRNA
GI: 32330899


mRNA, partial cds




194. Influenza A virus
844 bp
AF362820.1


(A/human/Taiwan/0095/96(H3N2)) hemagglutinin
linear mRNA
GI: 15055140


(HA) mRNA, partial cds




195. Influenza A virus
791 bp
AY604828.1


(A/Taiwan/0097/2003(H3N2)) hemagglutinin
linear mRNA
GI: 50727536


mRNA, partial cds




196. Influenza A virus (A/Taiwan/0104/2001
297 bp
AY303706.1


(H3N2)) polymerase basic protein 1 (PB1)
linear mRNA
GI: 32330901


mRNA, partial cds




197. Influenza A virus
844 bp
AF362805.1


(A/human/Taiwan/0118/98(H3N2)) hemagglutinin
linear mRNA
GI: 15055110


(HA) mRNA, partial cds




198. Influenza A virus
791 bp
AY604823.1


(A/Taiwan/0122/2003(H3N2)) hemagglutinin
linear mRNA
GI: 50727526


mRNA, partial cds




199. Influenza A virus
844 bp
AF362806.1


(A/human/Taiwan/0149/00(H3N2)) hemagglutinin
linear mRNA
GI: 15055112


(HA) mRNA, partial cds




200. Influenza A virus (A/Taiwan/0275/2000
297 bp
AY303712.1


(H3N2)) polymerase basic protein 1 (PB1)
linear mRNA
GI: 32330913


mRNA, partial cds




201. Influenza A virus (A/Taiwan/0275/2000
844 bp
AY303713.1


(H3N2)) hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32330915


202. Influenza A virus
844 bp
AF362807.1


(A/human/Taiwan/0293/98(H3N2)) hemagglutinin
linear mRNA
GI: 15055114


(HA) mRNA, partial cds




203. Influenza A virus (A/Taiwan/0346/98
297 bp
AY303715.1


(H3N2)) polymerase basic protein 1 (PB1)
linear mRNA
GI: 32330919


mRNA, partial cds




204. Influenza A virus (A/Taiwan/0379/2000
297 bp
AY303716.1


(H3N2)) polymerase basic protein 1 (PB1)
linear mRNA
GI: 32330921


mRNA, partial cds




205. Influenza A virus (A/Taiwan/0379/2000
844 bp
AY303717.1


(H3N2)) hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32330923


206. Influenza A virus
791 bp
AY625729.1


(A/Taiwan/0388/2001(H3N2)) hemagglutinin
linear mRNA
GI: 50604415


(HA) mRNA, partial cds




207. Influenza A virus
844 bp
AF362808.1


(A/human/Taiwan/0389/99(H3N2)) hemagglutinin
linear mRNA
GI: 15055116


(HA) mRNA, partial cds




208. Influenza A virus
844 bp
AF362809.1


(A/human/Taiwan/0423/98(H3N2)) hemagglutinin
linear mRNA
GI: 15055118


(HA) mRNA, partial cds




209. Influenza A virus (A/Taiwan/0423/98
297 bp
AY303718.1


(H3N2)) polymerase basic protein 1 (PB1)
linear mRNA
GI: 32330925


mRNA, partial cds




210. Influenza A virus
844 bp
AF362810.1


(A/human/Taiwan/0464/98(H3N2)) hemagglutinin
linear mRNA
GI: 15055120


(HA) mRNA, partial cds




211. Influenza A virus (A/Taiwan/0464/98
297 bp
AY303719.1


(H3N2)) polymerase basic protein 1 (PB1)
linear mRNA
GI: 32330927


mRNA, partial cds




212. Influenza A virus
791 bp
AY625730.1


(A/Taiwan/0568/2001(H3N2)) hemagglutinin
linear mRNA
GI: 50604440


(HA) mRNA, partial cds




213. Influenza A virus
791 bp
AY604822.1


(A/Taiwan/0570/2003(H3N2)) hemagglutinin
linear mRNA
GI: 50727524


mRNA, partial cds




214. Influenza A virus
791 bp
AY604827.1


(A/Taiwan/0572/2003(H3N2)) hemagglutinin
linear mRNA
GI: 50727534


mRNA, partial cds




215. Influenza A virus
791 bp
AY604821.1


(A/Taiwan/0578/2003(H3N2)) hemagglutinin
linear mRNA
GI: 50727522


mRNA, partial cds




216. Influenza A virus
791 bp
AY604820.1


(A/Taiwan/0583/2003(H3N2)) hemagglutinin
linear mRNA
GI: 50727520


mRNA, partial cds




217. Influenza A virus (A/Taiwan/0646/2000
297 bp
AY303722.1


(H3N2)) polymerase basic protein 1 (PB1)
linear mRNA
GI: 32330933


mRNA, partial cds




218. Influenza A virus (A/Taiwan/0646/2000
844 bp
AY303723.1


(H3N2)) hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32330935


219. Influenza A virus
844 bp
AF362811.1


(A/human/Taiwan/0830/99(H3N2)) hemagglutinin
linear mRNA
GI: 15055122


(HA) mRNA, partial cds




220. Influenza A virus
791 bp
AY625731.1


(A/Taiwan/0964/2001(H3N2)) hemagglutinin
linear mRNA
GI: 50604469


(HA) mRNA, partial cds




221. Influenza A virus
844 bp
AF362812.1


(A/human/Taiwan/1008/99(H3N2)) hemagglutinin
linear mRNA
GI: 15055124


(HA) mRNA, partial cds




222. Influenza A virus (A/Taiwan/1008/99
297 bp
AY303725.1


(H3N2)) polymerase basic protein 1 (PB1)
linear mRNA
GI: 32330939


mRNA, partial cds




223. Influenza A virus
750 bp
EU068138.1


(A/Taiwan/1219/2004(H3N2)) hemagglutinin
linear mRNA
GI: 158452149


(HA) mRNA, partial cds




224. Influenza A virus
750 bp
EU068125.1


(A/Taiwan/1315/2005(H3N2)) hemagglutinin
linear mRNA
GI: 158452123


(HA) mRNA, partial cds




225. Influenza A virus
750 bp
EU068153.1


(A/Taiwan/1511/2004(H3N2)) hemagglutinin
linear mRNA
GI: 158452179


(HA) mRNA, partial cds




226. Influenza A virus
750 bp
EU068119.1


(A/Taiwan/1533/2003(H3N2)) hemagglutinin
linear mRNA
GI: 158452111


(HA) mRNA, partial cds




227. Influenza A virus
844 bp
AF362813.1


(A/human/Taiwan/1537/99(H3N2)) hemagglutinin
linear mRNA
GI: 15055126


(HA) mRNA, partial cds




228. Influenza A virus (A/Taiwan/1537/99
297 bp
AY303728.1


(H3N2)) polymerase basic protein 1 (PB1)
linear mRNA
GI: 32330945


mRNA, partial cds




229. Influenza A virus
791 bp
AY604826.1


(A/Taiwan/1566/2003(H3N2)) hemagglutinin
linear mRNA
GI: 50727532


mRNA, partial cds




230. Influenza A virus
791 bp
AY604819.1


(A/Taiwan/1568/2003(H3N2)) hemagglutinin
linear mRNA
GI: 50727518


mRNA, partial cds




231. Influenza A virus
750 bp
EU068116.1


(A/Taiwan/158/2003(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 158452105


mRNA, partial cds




232. Influenza A virus
875 bp
AF138709.2


(A/Taiwan/1600/96(H3N2)) matrix protein M1
linear mRNA
GI: 4996869


(M) mRNA, partial cds




233. Influenza A virus
750 bp
EU068117.1


(A/Taiwan/1613/2003(H3N2)) hemagglutinin
linear mRNA
GI: 158452107


(HA) mRNA, partial cds




234. Influenza A virus
750 bp
EU068148.1


(A/Taiwan/1651/2004(H3N2)) hemagglutinin
linear mRNA
GI: 158452169


(HA) mRNA, partial cds




235. Influenza A virus
844 bp
AF362814.1


(A/human/Taiwan/1748/97(H3N2)) hemagglutinin
linear mRNA
GI: 15055128


(HA) mRNA, partial cds




236. Influenza A virus (A/Taiwan/1748/97
297 bp
AY303729.1


(H3N2)) polymerase basic protein 1 (PB1)
linear mRNA
GI: 32330947


mRNA, partial cds




237. Influenza A virus
872 bp
AF138707.2


(A/Taiwan/179/96(H3N2)) matrix protein M1
linear mRNA
GI: 4996865


(M) mRNA, partial cds




238. Influenza A virus
750 bp
EU068139.1


(A/Taiwan/1817/2004(H3N2)) hemagglutinin
linear mRNA
GI: 158452151


(HA) mRNA, partial cds




239. Influenza A virus
750 bp
EU068154.1


(A/Taiwan/1904/2003(H3N2)) hemagglutinin
linear mRNA
GI: 158452181


(HA) mRNA, partial cds




240. Influenza A virus
750 bp
EU068155.1


(A/Taiwan/1921/2003(H3N2)) hemagglutinin
linear mRNA
GI: 158452183


(HA) mRNA, partial cds




241. Influenza A virus
844 bp
AF362815.1


(A/human/Taiwan/1986/96(H3N2)) hemagglutinin
linear mRNA
GI: 15055130


(HA) mRNA, partial cds




242. Influenza A virus (A/Taiwan/1990/96
297 bp
AY303730.1


(H3N2)) polymerase basic protein 1 (PB1)
linear mRNA
GI: 32330949


mRNA, partial cds




243. Influenza A virus (A/Taiwan/1990/96
844 bp
AY303731.1


(H3N2)) hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32330951


244. Influenza A virus
861 bp
AF139938.1


(A/Taiwan/20/98(H3N2)) H3 hemagglutinin (HA)
linear mRNA
GI: 4972940


mRNA, partial cds




245. Influenza A virus
392 bp
AF140627.1


(A/Taiwan/20/98(H3N2)) N2 neuraminidase (NA)
linear mRNA
GI: 4972988


mRNA, partial cds




246. Influenza A virus
875 bp
AF138715.2


(A/Taiwan/20/98(H3N2)) matrix protein M1 (M)
linear mRNA
GI: 4996879


mRNA, partial cds




247. Influenza A virus
844 bp
AF362816.1


(A/human/Taiwan/2031/97(H3N2)) hemagglutinin
linear mRNA
GI: 15055132


(HA) mRNA, partial cds




248. Influenza A virus
861 bp
AF139937.1


(A/Taiwan/2034/96(H3N2)) H3 hemagglutinin
linear mRNA
GI: 4972938


(HA) mRNA, partial cds




249. Influenza A virus
392 bp
AF140620.1


(A/Taiwan/2034/96(H3N2)) N2 neuraminidase
linear mRNA
GI: 4972974


(NA) mRNA, partial cds




250. Influenza A virus
297 bp
AY303732.1


(A/Taiwan/2034/96(H3N2)) polymerase basic
linear mRNA
GI: 32330953


protein 1 (PB1) mRNA, partial cds




251. Influenza A virus
791 bp
AY604818.1


(A/Taiwan/2040/2003(H3N2)) hemagglutinin
linear mRNA
GI: 50727516


mRNA, partial cds




252. Influenza A virus
750 bp
EU068131.1


(A/Taiwan/2072/2006(H3N2)) hemagglutinin
linear mRNA
GI: 158452135


(HA) mRNA, partial cds




253. Influenza A virus
861 bp
AF139934.1


(A/Taiwan/21/98(H3N2)) H3 hemagglutinin (HA)
linear mRNA
GI: 4972932


mRNA, partial cds




254. Influenza A virus
392 bp
AF140624.1


(A/Taiwan/21/98(H3N2)) N2 neuraminidase (NA)
linear mRNA
GI: 4972982


mRNA, partial cds




255. Influenza A virus
875 bp
AF138716.2


(A/Taiwan/21/98(H3N2)) matrix protein M1 (M)
linear mRNA
GI: 4996881


mRNA, partial cds




256. Influenza A virus
861 bp
AF139932.1


(A/Taiwan/2191/96(H3N2)) H3 hemagglutinin
linear mRNA
GI: 4972928


(HA) mRNA, partial cds




257. Influenza A virus
392 bp
AF140622.1


(A/Taiwan/2191/96(H3N2)) N2 neuraminidase
linear mRNA
GI: 4972978


(NA) mRNA, partial cds




258. Influenza A virus
875 bp
AF138711.3


(A/Taiwan/2191/96(H3N2)) matrix protein M1
linear mRNA
GI: 156147502


(M) mRNA, partial cds




259. Influenza A virus
861 bp
AF139936.1


(A/Taiwan/2192/96(H3N2)) H3 hemagglutinin
linear mRNA
GI: 4972936


(HA) mRNA, partial cds




260. Influenza A virus
392 bp
AF140626.1


(A/Taiwan/2192/96(H3N2)) N2 neuraminidase
linear mRNA
GI: 4972986


(NA) mRNA, partial cds




261. Influenza A virus (A/Taiwan/2195/96
297 bp
AY303735.1


(H3N2)) polymerase basic protein 1 (PB1)
linear mRNA
GI: 32330959


mRNA, partial cds




262. Influenza A virus (A/Taiwan/2195/96
844 bp
AY303736.1


(H3N2)) hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32330961


263. Influenza A virus
875 bp
AF138718.2


(A/Taiwan/224/98(H3N2)) matrix protein M1
linear mRNA
GI: 4996885


(M) mRNA, partial cds




264. Influenza A virus
844 bp
AF362817.1


(A/human/Taiwan/2548/99(H3N2)) hemagglutinin
linear mRNA
GI: 15055134


(HA) mRNA, partial cds




265. Influenza A virus
750 bp
EU068120.1


(A/Taiwan/268/2005(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 158452113


mRNA, partial cds




266. Influenza A virus
750 bp
EU068149.1


(A/Taiwan/3008/2004(H3N2)) hemagglutinin
linear mRNA
GI: 158452171


(HA) mRNA, partial cds




267. Influenza A virus
750 bp
EU068152.1


(A/Taiwan/3075/2003(H3N2)) hemagglutinin
linear mRNA
GI: 158452177


(HA) mRNA, partial cds




268. Influenza A virus
940 bp
AF362818.1


(A/human/Taiwan/3083/00(H3N2)) hemagglutinin
linear mRNA
GI: 15055136


(HA) mRNA, partial cds




269. Influenza A virus
791 bp
AY604811.1


(A/Taiwan/3131/2002(H3N2)) hemagglutinin
linear mRNA
GI: 50727502


mRNA, partial cds




270. Influenza A virus
750 bp
EU068145.1


(A/Taiwan/3154/2004(H3N2)) hemagglutinin
linear mRNA
GI: 158452163


(HA) mRNA, partial cds




271. Influenza A virus
750 bp
EU068141.1


(A/Taiwan/3187/2004(H3N2)) hemagglutinin
linear mRNA
GI: 158452155


(HA) mRNA, partial cds




272. Influenza A virus
750 bp
EU068134.1


(A/Taiwan/3245/2004(H3N2)) hemagglutinin
linear mRNA
GI: 158452141


(HA) mRNA, partial cds




273. Influenza A virus
750 bp
EU068133.1


(A/Taiwan/3294/2005(H3N2)) hemagglutinin
linear mRNA
GI: 158452139


(HA) mRNA, partial cds




274. Influenza A virus
861 bp
AF139935.1


(A/Taiwan/3351/97(H3N2)) H3 hemagglutinin
linear mRNA
GI: 4972934


(HA) mRNA, partial cds




275. Influenza A virus
392 bp
AF140625.1


(A/Taiwan/3351/97(H3N2)) N2 neuraminidase
linear mRNA
GI: 4972984


(NA) mRNA, partial cds




276. Influenza A virus
875 bp
AF138713.2


(A/Taiwan/3351/97(H3N2)) matrix protein M1
linear mRNA
GI: 4996875


(M) mRNA, partial cds




277. Influenza A virus
297 bp
AY303738.1


(A/Taiwan/3351/97(H3N2)) polymerase basic
linear mRNA
GI: 32330965


protein 1 (PB1) mRNA, partial cds




278. Influenza A virus
750 bp
EU068132.1


(A/Taiwan/3387/2005(H3N2)) hemagglutinin
linear mRNA
GI: 158452137


(HA) mRNA, partial cds




279. Influenza A virus (A/Taiwan/3396/97
297 bp
AY303742.1


(H3N2)) polymerase basic protein 1 (PB1)
linear mRNA
GI: 32330973


mRNA, partial cds




280. Influenza A virus (A/Taiwan/3396/97
844 bp
AY303743.1


(H3N2)) hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32330975


281. Influenza A virus
861 bp
AF139930.1


(A/Taiwan/3427/97(H3N2)) H3 hemagglutinin
linear mRNA
GI: 4972924


(HA) mRNA, partial cds




282. Influenza A virus
392 bp
AF140619.1


(A/Taiwan/3427/97(H3N2)) N2 neuraminidase
linear mRNA
GI: 4972972


(NA) mRNA, partial cds




283. Influenza A virus
861 bp
AF139940.1


(A/Taiwan/346/98(H3N2)) H3 hemagglutinin
linear mRNA
GI: 4972944


(HA) mRNA, partial cds




284. Influenza A virus
392 bp
AF140787.1


(A/Taiwan/346/98(H3N2)) N2 neuraminidase
linear mRNA
GI: 4972992


(NA) mRNA, partial cds




285. Influenza A virus
875 bp
AF138719.2


(A/Taiwan/346/98(H3N2)) matrix protein M1
linear mRNA
GI: 4996887


(M) mRNA, partial cds




286. Influenza A virus
942 bp
AF362819.1


(A/human/Taiwan/3460/00(H3N2)) truncated
linear mRNA
GI: 15055138


hemagglutinin (HA) mRNA, partial cds




287. Influenza A virus
861 bp
AF139933.1


(A/Taiwan/3469/97(H3N2)) H3 hemagglutinin
linear mRNA
GI: 4972930


(HA) mRNA, partial cds




288. Influenza A virus
392 bp
AF140623.1


(A/Taiwan/3469/97(H3N2)) N2 neuraminidase
linear mRNA
GI: 4972980


(NA) mRNA, partial cds




289. Influenza A virus
875 bp
AF138714.2


(A/Taiwan/3469/97(H3N2)) matrix protein M1
linear mRNA
GI: 4996877


(M) mRNA, partial cds




290. Influenza A virus (A/Taiwan/3503/97
297 bp
AY303744.1


(H3N2)) polymerase basic protein 1 (PB1)
linear mRNA
GI: 32330977


mRNA, partial cds




291. Influenza A virus (A/Taiwan/3503/97
844 bp
AY303745.1


(H3N2)) hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32330979


292. Influenza A virus
919 bp
AF138712.1


(A/Taiwan/3513/96(H3N2)) matrix protein M1
linear mRNA
GI: 4928900


(M) mRNA, partial cds




293. Influenza A virus
861 bp
AF139931.1


(A/Taiwan/3513/97(H3N2)) H3 hemagglutinin
linear mRNA
GI: 4972926


(HA) mRNA, partial cds




294. Influenza A virus
392 bp
AF140621.1


(A/Taiwan/3513/97(H3N2)) N2 neuraminidase
linear mRNA
GI: 4972976


(NA) mRNA, partial cds




295. Influenza A virus
791 bp
AY604814.1


(A/Taiwan/3744/2002(H3N2)) hemagglutinin
linear mRNA
GI: 50727508


mRNA, partial cds




296. Influenza A virus
940 bp
AF362804.1


(A/human/Taiwan/3760/00(H3N2)) hemagglutinin
linear mRNA
GI: 15055108


(HA) mRNA, partial cds




297. Influenza A virus (A/Taiwan/3896/2001
561 bp
AY303747.1


(H1N1)) hemagglutinin (HA) mRNA, partial cds
linear mRNA
GI: 32330983


298. Influenza A virus
791 bp
AY604825.1


(A/Taiwan/4050/2003(H3N2)) hemagglutinin
linear mRNA
GI: 50727530


mRNA, partial cds




299. Influenza A virus
791 bp
AY604824.1


(A/Taiwan/4063/2003(H3N2)) hemagglutinin
linear mRNA
GI: 50727528


mRNA, partial cds




300. Influenza A virus
750 bp
EU068137.1


(A/Taiwan/41/2004(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 158452147


mRNA, partial cds




301. Influenza A virus
861 bp
AF139939.1


(A/Taiwan/45/98(H3N2)) H3 hemagglutinin (HA)
linear mRNA
GI: 4972942


mRNA, partial cds




302. Influenza A virus
392 bp
AF140628.1


(A/Taiwan/45/98(H3N2)) N2 neuraminidase (NA)
linear mRNA
GI: 4972990


mRNA, partial cds




303. Influenza A virus
875 bp
AF138717.2


(A/Taiwan/45/98(H3N2)) matrix protein M1 (M)
linear mRNA
GI: 4996883


mRNA, partial cds




304. Influenza A virus
750 bp
EU068114.1


(A/Taiwan/4548/2003(H3N2)) hemagglutinin
linear mRNA
GI: 158452101


(HA) mRNA, partial cds




305. Influenza A virus
791 bp
AY604813.1


(A/Taiwan/4673/2002(H3N2)) hemagglutinin
linear mRNA
GI: 50727506


mRNA, partial cds




306. Influenza A virus
791 bp
AY604812.1


(A/Taiwan/4680/2002(H3N2)) hemagglutinin
linear mRNA
GI: 50727504


mRNA, partial cds




307. Influenza A virus
750 bp
EU068136.1


(A/Taiwan/4735/2004(H3N2)) hemagglutinin
linear mRNA
GI: 158452145


(HA) mRNA, partial cds




308. Influenza A virus
750 bp
EU068142.1


(A/Taiwan/4829/2005(H3N2)) hemagglutinin
linear mRNA
GI: 158452157


(HA) mRNA, partial cds




309. Influenza A virus
750 bp
EU068130.1


(A/Taiwan/4836/2005(H3N2)) hemagglutinin
linear mRNA
GI: 158452133


(HA) mRNA, partial cds




310. Influenza A virus
750 bp
EU068143.1


(A/Taiwan/4865/2005(H3N2)) hemagglutinin
linear mRNA
GI: 158452159


(HA) mRNA, partial cds




311. Influenza A virus
750 bp
EU068121.1


(A/Taiwan/4883/2005(H3N2)) hemagglutinin
linear mRNA
GI: 158452115


(HA) mRNA, partial cds




312. Influenza A virus
791 bp
AY604809.1


(A/Taiwan/4938/2002(H3N2)) hemagglutinin
linear mRNA
GI: 50727498


mRNA, partial cds




313. Influenza A virus
791 bp
AY604815.1


(A/Taiwan/4954/2002(H3N2)) hemagglutinin
linear mRNA
GI: 50727510


mRNA, partial cds




314. Influenza A virus
791 bp
AY604810.1


(A/Taiwan/4963/2002(H3N2)) hemagglutinin
linear mRNA
GI: 50727500


mRNA, partial cds




315. Influenza A virus
750 bp
EU068122.1


(A/Taiwan/4987/2005(H3N2)) hemagglutinin
linear mRNA
GI: 158452117


(HA) mRNA, partial cds




316. Influenza A virus
750 bp
EU068127.1


(A/Taiwan/4990/2005(H3N2)) hemagglutinin
linear mRNA
GI: 158452127


(HA) mRNA, partial cds




317. Influenza A virus
750 bp
EU068118.1


(A/Taiwan/5/2003(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 158452109


mRNA, partial cds




318. Influenza A virus
791 bp
AY604816.1


(A/Taiwan/5153/2002(H3N2)) hemagglutinin
linear mRNA
GI: 50727512


mRNA, partial cds




319. Influenza A virus
750 bp
EU068128.1


(A/Taiwan/5267/2005(H3N2)) hemagglutinin
linear mRNA
GI: 158452129


(HA) mRNA, partial cds




320. Influenza A virus
750 bp
EU068146.1


(A/Taiwan/556/2004(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 158452165


mRNA, partial cds




321. Influenza A virus
750 bp
EU068126.1


(A/Taiwan/5694/2005(H3N2)) hemagglutinin
linear mRNA
GI: 158452125


(HA) mRNA, partial cds




322. Influenza A virus
750 bp
EU068147.1


(A/Taiwan/587/2004(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 158452167


mRNA, partial cds




323. Influenza A virus
750 bp
EU068151.1


(A/Taiwan/592/2004(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 158452175


mRNA, partial cds




324. Influenza A virus
791 bp
AY604829.1


(A/Taiwan/7099/2003(H3N2)) hemagglutinin
linear mRNA
GI: 50727538


mRNA, partial cds




325. Influenza A virus
791 bp
AY604830.1


(A/Taiwan/7100/2003(H3N2)) hemagglutinin
linear mRNA
GI: 50727540


mRNA, partial cds




326. Influenza A virus
750 bp
EU068150.1


(A/Taiwan/7196/2003(H3N2)) hemagglutinin
linear mRNA
GI: 158452173


(HA) mRNA, partial cds




327. Influenza A virus
750 bp
EU068135.1


(A/Taiwan/7568/2004(H3N2)) hemagglutinin
linear mRNA
GI: 158452143


(HA) mRNA, partial cds




328. Influenza A virus
750 bp
EU068144.1


(A/Taiwan/7601/2005(H3N2)) hemagglutinin
linear mRNA
GI: 158452161


(HA) mRNA, partial cds




329. Influenza A virus
750 bp
EU068124.1


(A/Taiwan/7681/2005(H3N2)) hemagglutinin
linear mRNA
GI: 158452121


(HA) mRNA, partial cds




330. Influenza A virus
750 bp
EU068123.1


(A/Taiwan/7702/2005(H3N2)) hemagglutinin
linear mRNA
GI: 158452119


(HA) mRNA, partial cds




331. Influenza A virus
750 bp
EU068129.1


(A/Taiwan/7873/2005(H3N2)) hemagglutinin
linear mRNA
GI: 158452131


(HA) mRNA, partial cds




332. Influenza A virus
750 bp
EU068115.1


(A/Taiwan/8/2003(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 158452103


mRNA, partial cds




333. Influenza A virus
750 bp
EU068140.1


(A/Taiwan/93/2004(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 158452153


mRNA, partial cds




334. Influenza A virus
528 bp
AY962016.1


(A/Taoyuan/108/02(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138189


mRNA, partial cds




335. Influenza A virus
754 bp
AY973338.1


(A/Taoyuan/108/02(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673232


mRNA, partial cds




336. Influenza A virus
882 bp
AY986998.1


(A/Taoyuan/108/02(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728123


mRNA, partial cds




337. Influenza A virus
1,410 bp
EU021285.1


(A/Thailand/CU124/2006(H3N2)) neuraminidase
linear mRNA
GI: 154224724


(NA) mRNA, complete cds




338. Influenza A virus
1,701 bp
EU021284.1


(A/Thailand/CU124/2006(H3N2)) hemagglutinin
linear mRNA
GI: 154224795


(HA) mRNA, complete cds




339. Influenza A virus
1,410 bp
EU021275.1


(A/Thailand/CU228/2006(H3N2)) neuraminidase
linear mRNA
GI: 154224714


(NA) mRNA, complete cds




340. Influenza A virus
1,701 bp
EU021274.1


(A/Thailand/CU228/2006(H3N2)) hemagglutinin
linear mRNA
GI: 154224785


(HA) mRNA, complete cds




341. Influenza A virus
1,347 bp
EU021267.1


(A/Thailand/CU23/2006(H3N2)) neuraminidase
linear mRNA
GI: 154224706


(NA) mRNA, partial cds




342. Influenza A virus
1,701 bp
EU021266.1


(A/Thailand/CU23/2006(H3N2)) hemagglutinin
linear mRNA
GI: 154224777


(HA) mRNA, complete cds




343. Influenza A virus
1,410 bp
EU021283.1


(A/Thailand/CU231/2006(H3N2)) neuraminidase
linear mRNA
GI: 154224722


(NA) mRNA, complete cds




344. Influenza A virus
1,701 bp
EU021282.1


(A/Thailand/CU231/2006(H3N2)) hemagglutinin
linear mRNA
GI: 154224793


(HA) mRNA, complete cds




345. Influenza A virus
1,410 bp
EU021279.1


(A/Thailand/CU259/2006(H3N2)) neuraminidase
linear mRNA
GI: 154224718


(NA) mRNA, complete cds




346. Influenza A virus
1,701 bp
EU021278.1


(A/Thailand/CU259/2006(H3N2)) hemagglutinin
linear mRNA
GI: 154224789


(HA) mRNA, complete cds




347. Influenza A virus
1,410 bp
EU021281.1


(A/Thailand/CU260/2006(H3N2)) neuraminidase
linear mRNA
GI: 154224720


(NA) mRNA, complete cds




348. Influenza A virus
1,129 bp
EU021280.1


(A/Thailand/CU260/2006(H3N2)) hemagglutinin
linear mRNA
GI: 154224791


(HA) mRNA, partial cds




349. Influenza A virus
1,410 bp
EU021271.1


(A/Thailand/CU272/2007(H3N2)) neuraminidase
linear mRNA
GI: 154224710


(NA) mRNA, complete cds




350. Influenza A virus
1,701 bp
EU021270.1


(A/Thailand/CU272/2007(H3N2)) hemagglutinin
linear mRNA
GI: 154224781


(HA) mRNA, complete cds




351. Influenza A virus
1,410 bp
EU021273.1


(A/Thailand/CU280/2007(H3N2)) neuraminidase
linear mRNA
GI: 154224712


(NA) mRNA, complete cds




352. Influenza A virus
1,701 bp
EU021272.1


(A/Thailand/CU280/2007(H3N2)) hemagglutinin
linear mRNA
GI: 154224783


(HA) mRNA, complete cds




353. Influenza A virus
1,410 bp
EU021277.1


(A/Thailand/CU282/2007(H3N2)) neuraminidase
linear mRNA
GI: 154224716


(NA) mRNA, complete cds




354. Influenza A virus
1,701 bp
EU021276.1


(A/Thailand/CU282/2007(H3N2)) hemagglutinin
linear mRNA
GI: 154224787


(HA) mRNA, complete cds




355. Influenza A virus
1,413 bp
EU021265.1


(A/Thailand/CU32/2006(H1N1)) neuraminidase
linear mRNA
GI: 154224704


(NA) mRNA, complete cds




361. Influenza A virus
1,410 bp
EU021269.1


(A/Thailand/CU46/2006(H3N2)) neuraminidase
linear mRNA
GI: 154224708


(NA) mRNA, complete cds




362. Influenza A virus
1,701 bp
EU021268.1


(A/Thailand/CU46/2006(H3N2)) hemagglutinin
linear mRNA
GI: 154224779


(HA) mRNA, complete cds




377. Influenza A virus
987 bp
U77837.1


(A/Tottori/849AM1AL3/1994(H3N2))
linear mRNA
GI: 2992515


hemagglutinin (HA) mRNA, partial cds




378. Influenza A virus
987 bp
U77833.1


(A/Tottori/849AM2/1994(H3N2)) hemagglutinin
linear mRNA
GI: 2992507


(HA) mRNA, partial cds




379. Influenza A virus
987 bp
U77839.1


(A/Tottori/849AM2AL3/1994(H3N2))
linear mRNA
GI: 2992519


hemagglutinin (HA) mRNA, partial cds




380. Influenza A virus
987 bp
U77835.1


(A/Tottori/849AM4/1994(H3N2)) hemagglutinin
linear mRNA
GI: 2992511


(HA) mRNA, partial cds




382. Influenza A virus
987 bp
U77834.1


(A/Tottori/872AM2/1994(H3N2)) hemagglutinin
linear mRNA
GI: 2992509


(HA) mRNA, partial cds




383. Influenza A virus
987 bp
U77840.1


(A/Tottori/872AM2AL3/1994(H3N2))
linear mRNA
GI: 2992521


hemagglutinin (HA) mRNA, partial cds




384. Influenza A virus
987 bp
U77836.1


(A/Tottori/872AM4/1994(H3N2)) hemagglutinin
linear mRNA
GI: 2992513


(HA) mRNA, partial cds




385. Influenza A virus
987 bp
U77832.1


(A/Tottori/872K4/1994(H3N2)) hemagglutinin
linear mRNA
GI: 2992505


(HA) mRNA, partial cds




386. Influenza A virus (A/United
987 bp
AF501529.1


Kingdom/26554/99(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 21314314


mRNA, partial cds




387. Influenza A virus (A/United
987 bp
AF501527.1


Kingdom/34300/99(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 21314310


mRNA, partial cds




388. Influenza A virus
987 bp
AF501533.1


(A/Utah/20997/99(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 21314322


mRNA, partial cds




389. Influenza A virus (A/Victoria/3/75)
1,565 bp
AF072545.1


segment 5 nucleoprotein mRNA, complete cds
linear mRNA
GI: 4218933


390. Influenza A virus
1,762 bp
AF017270.2


(A/Vienna/47/96M(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 14286338


mRNA, complete cds




391. Influenza A virus
1,762 bp
AF017272.2


(A/Vienna/47/96V(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 15004991


mRNA, complete cds




392. Influenza A virus
1,069 bp
AF017271.1


(A/Vienna/81/96V(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 2407251


mRNA, partial cds




393. Influenza A virus
987 bp
AF501532.1


(A/Virginia/21712/99(H3N2)) hemagglutinin
linear mRNA
GI: 21314320


(HA) mRNA, partial cds




394. Influenza A virus
987 bp
AF501515.1


(A/Virginia/21716/99(H3N2)) hemagglutinin
linear mRNA
GI: 21314286


(HA) mRNA, partial cds




395. Influenza A virus
987 bp
AF501530.1


(A/Virginia/21735/99(H3N2)) hemagglutinin
linear mRNA
GI: 21314316


(HA) mRNA, partial cds




396. Influenza A virus
987 bp
AF501524.1


(A/Virginia/21743/99(H3N2)) hemagglutinin
linear mRNA
GI: 21314304


(HA) mRNA, partial cds




397. Influenza A virus
987 bp
AF501519.1


(A/Virginia/21754/99(H3N2)) hemagglutinin
linear mRNA
GI: 21314294


(HA) mRNA, partial cds




398. Influenza A virus
987 bp
AF501523.1


(A/Virginia/21799/99(H3N2)) hemagglutinin
linear mRNA
GI: 21314302


(HA) mRNA, partial cds




399. Influenza A virus
987 bp
AF501525.1


(A/Virginia/21817/99(H3N2)) hemagglutinin
linear mRNA
GI: 21314306


(HA) mRNA, partial cds




400. Influenza A virus
987 bp
AF501520.1


(A/Virginia/21822/99(H3N2)) hemagglutinin
linear mRNA
GI: 21314296


(HA) mRNA, partial cds




401. Influenza A virus
987 bp
AF501528.1


(A/Virginia/21828/99(H3N2)) hemagglutinin
linear mRNA
GI: 21314312


(HA) mRNA, partial cds




402. Influenza A virus
987 bp
AF501517.1


(A/Virginia/21833/99(H3N2)) hemagglutinin
linear mRNA
GI: 21314290


(HA) mRNA, partial cds




403. Influenza A virus
987 bp
AF501522.1


(A/Virginia/21845/99(H3N2)) hemagglutinin
linear mRNA
GI: 21314300


(HA) mRNA, partial cds




404. Influenza A virus
987 bp
AF501535.1


(A/Virginia/21847/99(H3N2)) hemagglutinin
linear mRNA
GI: 21314326


(HA) mRNA, partial cds




405. Influenza A virus
987 bp
AF501521.1


(A/Virginia/G1/99(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 21314298


mRNA, partial cds




406. Influenza A virus
755 bp
AY973339.1


(A/Yilan/508/03(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673234


mRNA, partial cds




407. Influenza A virus
882 bp
AY986999.1


(A/Yilan/508/03(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728125


mRNA, partial cds




408. Influenza A virus
740 bp
AY962015.1


(A/Yilan/513/03(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138187


mRNA, partial cds




409. Influenza A virus
396 bp
AY973340.1


(A/Yilan/513/03(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673236


mRNA, partial cds




410. Influenza A virus
882 bp
AY987000.1


(A/Yilan/513/03(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728127


mRNA, partial cds




411. Influenza A virus
511 bp
AY962010.1


(A/Yilan/515/03(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138177


mRNA, partial cds




412. Influenza A virus
394 bp
AY973341.1


(A/Yilan/515/03(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673238


mRNA, partial cds




413. Influenza A virus
882 bp
AY987001.1


(A/Yilan/516/03(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728129


mRNA, partial cds




414. Influenza A virus
530 bp
AY962006.1


(A/Yilan/518/03(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138169


mRNA, partial cds




415. Influenza A virus
397 bp
AY973342.1


(A/Yilan/518/03(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673240


mRNA, partial cds




416. Influenza A virus
882 bp
AY987002.1


(A/Yilan/518/03(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728131


mRNA, partial cds




417. Influenza A virus
777 bp
AY962002.1


(A/Yilan/538/04(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138161


mRNA, partial cds




418. Influenza A virus
783 bp
AY973343.1


(A/Yilan/538/04(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673242


mRNA, partial cds




419. Influenza A virus
882 bp
AY987003.1


(A/Yilan/538/04(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728133


mRNA, partial cds




420. Influenza A virus
788 bp
AY962003.1


(A/Yilan/549/04(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138163


mRNA, partial cds




421. Influenza A virus
779 bp
AY973344.1


(A/Yilan/549/04(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673244


mRNA, partial cds




422. Influenza A virus
882 bp
AY987004.1


(A/Yilan/549/04(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728135


mRNA, partial cds




423. Influenza A virus
776 bp
AY962013.1


(A/Yilan/557/04(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138183


mRNA, partial cds




424. Influenza A virus
796 bp
AY973345.1


(A/Yilan/557/04(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673246


mRNA, partial cds




425. Influenza A virus
882 bp
AY987005.1


(A/Yilan/557/04(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728137


mRNA, partial cds




426. Influenza A virus
753 bp
AY962014.1


(A/Yilan/566/04(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 68138185


mRNA, partial cds




427. Influenza A virus
808 bp
AY973346.1


(A/Yilan/566/04(H3N2)) neuraminidase (NA)
linear mRNA
GI: 70673248


mRNA, partial cds




428. Influenza A virus
882 bp
AY987006.1


(A/Yilan/566/04(H3N2)) nucleoprotein (NP)
linear mRNA
GI: 70728139


mRNA, partial cds




429. Influenza A virus
987 bp
AY138513.1


(A/zhejiang/06/99(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 24895131


mRNA, partial cds




430. Influenza A virus
987 bp
AY138515.1


(A/zhejiang/10/98(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 24895149


mRNA, partial cds




431. Influenza A virus
987 bp
AY138516.1


(A/zhejiang/11/2002(H3N2)) hemagglutinin
linear mRNA
GI: 24895159


(HA) mRNA, partial cds




432. Influenza A virus
987 bp
AY138514.1


(A/zhejiang/12/99(H3N2)) hemagglutinin-like
linear mRNA
GI: 24895141


(HA) mRNA, partial sequence




433. Influenza A virus
987 bp
AY138519.1


(A/zhejiang/8/2002(H3N2)) hemagglutinin (HA)
linear mRNA
GI: 24895188


mRNA, partial cds




434. Influenza A virus H3N2 strain
840 bp
U65670.1


A/Akita/1/94 nonstructural protein 1 and
linear mRNA
GI: 3929405


nonstructural protein 2 mRNAs, complete cds




435. Influenza A virus H3N2 strain
840 bp
U65671.1


A/Akita/1/95 nonstructural protein 1 and
linear mRNA
GI: 3929408


nonstructural protein 2 mRNAs, complete cds




436. Influenza A virus H3N2 strain
840 bp
U65673.1


A/Shiga/20/95 nonstructural protein 1 and
linear mRNA
GI: 3929411


nonstructural protein 2 mRNAs, complete cds




437. Influenza A virus H3N2 strain
840 bp
U65674.1


A/Miyagi/69/95 nonstructural protein 1 and
linear mRNA
GI: 3929414


nonstructural protein 2 mRNAs, complete cds




438. Influenza A virus H3N2 strain
840 bp
U65672.1


A/Hebei/19/95 nonstructural protein 1 and
linear mRNA
GI: 6468319


nonstructural protein 2 mRNAs, complete cds




A/Aichi/69/1994(H3N2) haemagglutinin

U48446.1


A/Bangkok/1/1979 (H3N2) hemagglutinin (HA)

AF201843.1


A/Beijing/353/89(H3) hemagglutinin (HA)

U97740.1


A/Beijing/353/1989(H3N2) haemagglutinin

Z46391.1


A/chicken/Singapore/2002(H3N2) M2 protein

EU014143.1


A/Christ Hospital/231/82(H3N2))

U77830.1


hemagglutinin (HA)




A/duck/Eastern China/36/2002(H3N2) segment 6

EU429701.1


neuraminidase (NA)




A/duck/Eastern China/160/2003(H3N2) segment

EU429732.1


6 neuraminidase (NA)




A/duck/Eastern China/848/2003(H3N2) segment

EU429721.1


6 neuraminidase (NA)




A/duck/Eastern China/770/2003(H3N2) segment

EU429736.1


6 neuraminidase (NA)




A/duck/Eastern China/855/2003(H3N2) segment

EU429737.1


6 neuraminidase (NA)




A/duck/Eastern China/875/2003(H3N2) segment

EU429738.1


6 neuraminidase (NA)




A/duck/Eastern China/901/2003(H3N2) segment

EU429739.1


6 neuraminidase (NA)




A/duck/Eastern China/866/2003(H3N2) segment

EU429756.1


6 neuraminidase (NA)




A/duck/Eastern China/857/2003(H3N2) segment

EU429761.1


6 neuraminidase (NA)




A/duck/Eastern China/852/2003(H3N2) segment

EU429767.1


6 neuraminidase (NA)




A/duck/Eastern China/838/2003(H3N2) segment

EU429720.1


6 neuraminidase (NA)




A/duck/Eastern China/6/2004(H3N2) segment 6

EU429745.1


neuraminidase (NA)




A/duck/Eastern China/03/2005(H3N2) segment 6

EU429781.1


neuraminidase (NA)




A/duck/Eastern China/02/2006(H3N2) segment 6

EU429769.1


neuraminidase (NA)




A/duck/Eastern China/04/2006(H3N2) segment 6

EU429770.1


neuraminidase (NA)




A/duck/Eastern China/21/2006(H3N2) segment 6

EU429771.1


neuraminidase (NA)




A/duck/Eastern China/23/2006(H3N2) segment 6

EU429772.1


neuraminidase (NA)




A/duck/Eastern China/31/2006(H3N2) segment 6

EU429773.1


neuraminidase (NA)




A/duck/Eastern China/35/2006(H3N2) segment 6

EU429768.1


neuraminidase (NA)




A/duck/Eastern China/42/2006(H3N2) segment 6

EU429774.1


neuraminidase (NA)




A/duck/Eastern China/53/2006(H3N2) segment 6

EU429775.1


neuraminidase (NA)




A/duck/Eastern China/60/2006(H3N2) segment 6

EU429776.1


neuraminidase (NA)




A/duck/Eastern China/62/2006(H3N2) segment 6

EU429784.1


neuraminidase (NA)




A/duck/Eastern China/63/2006(H3N2) segment 6

EU429777.1


neuraminidase (NA)




A/duck/Eastern China/142/2006(H3N2) segment

EU429742.1


6 neuraminidase (NA)




A/Dunedin/4/1973 (H3N2) hemagglutinin (HA)

AF201842.1
















TABLE 9







Influenza H5N1 Antigens











GenBank/GI


Strain/Protein
Length
Accession No.





 1. Influenza A virus (A/chicken/Burkina
827 bp
AM503036.1


Faso/01.03/2006(H5N1)) mRNA for non-
linear mRNA
GI:147846308


structural protein (ns gene)




 2. Influenza A virus (A/chicken/Burkina
990 bp
AM503007.1


Faso/13.1/2006(H5N1)) partial mRNA for
linear mRNA
GI:147846250


matrix protein 1 (m1 gene)




 3. Influenza A virus (A/chicken/Burkina
1,529 bp
AM503029.1


Faso/13.1/2006(H5N1)) mRNA for nucleoprotein
linear mRNA
GI:147846294


(np gene)




 4. Influenza A virus (A/chicken/Burkina
827 bp
AM503037.1


Faso/13.1/2006(H5N1)) mRNA for non-
linear mRNA
GI:147846310


structural protein (ns gene)




 5. Influenza A virus (A/chicken/Burkina
2,169 bp
AM503046.1


Faso/13.1/2006(H5N1)) partial mRNA for
linear mRNA
GI:147846328


polymerase (pa gene)




 6. Influenza A virus (A/chicken/Burkina
2,259 bp
AM503056.1


Faso/13.1/2006(H5N1)) partial mRNA for
linear mRNA
GI:147846348


polymerase basic protein 1 (pb1 gene)




 7. Influenza A virus (A/chicken/Burkina
2,315 bp
AM503067.1


Faso/13.1/2006(H5N1)) partial mRNA for
linear mRNA
GI:147846859


polymerase basic protein 2 (pb2 gene)




 8. Influenza A virus
1,736 bp
DQ023145.1


(A/chicken/China/1/02(H5N1)) hemagglutinin
linear mRNA
GI:66775624


(HA) mRNA, complete cds




 9. Influenza A virus
1,509 bp
DQ023146.1


(A/chicken/China/1/02(H5N1)) nucleoprotein
linear mRNA
GI:66775626


(NP) mRNA, complete cds




 10. Influenza A virus
1,379 bp
DQ023147.1


(A/chicken/China/1/02(H5N1)) neuraminidase
linear mRNA
GI:66775628


(NA) mRNA, complete cds




 11. Influenza A virus
999 bp
DQ650660.1


(A/chicken/Crimea/04/2005(H5N1)) matrix
linear mRNA
GI:109692767


protein (M) mRNA, complete cds




 12. Influenza A virus
850 bp
DQ650662.1


(A/chicken/Crimea/04/2005(H5N1))
linear mRNA
GI:109692771


nonstructural protein (NS) mRNA, complete cds




 13. Influenza A virus
994 bp
DQ650664.1


(A/chicken/Crimea/08/2005(H5N1)) matrix
linear mRNA
GI:109692775


protein (M) mRNA, complete cds




 14. Influenza A virus
1,532 bp
DQ650666.1


(A/chicken/Crimea/08/2005(H5N1))
linear mRNA
GI:109692779


nucleoprotein (NP) mRNA, complete cds




 15. Influenza A virus
850 bp
DQ65066 7.1


(A/chicken/Crimea/08/2005(H5N1))
linear mRNA
GI:109692781


nonstructural protein (NS) mRNA, complete cds




 16. Influenza A virus
2,208 bp
DQ650668.1


(A/chicken/Crimea/08/2005(H5N1)) polymerase
linear mRNA
GI:109692783


acidic protein (PA) mRNA, complete cds




 17. Influenza A virus
2,305 bp
DQ650670.1


(A/chicken/Crimea/08/2005(H5N1)) polymerase
linear mRNA
GI:109692787


basic protein 2 (PB2) mRNA, complete cds




 18. Influenza A virus
1,015 bp
DQ676838.1


(A/chicken/Dovolnoe/03/2005(H5N1))
linear mRNA
GI:108782527


hemagglutinin (HA) mRNA, partial cds




 20. Influenza A virus
2,341 bp
DQ366327.1


(A/chicken/Guangxi/12/2004(H5N1)) polymerase
linear mRNA
GI:86753731


PB2 mRNA, complete cds




 21. Influenza A virus
2,341 bp
DQ366328.1


(A/chicken/Guangxi/12/2004(H5N1)) polymerase
linear mRNA
GI:86753741


PB1 mRNA, complete cds




 22. Influenza A virus
2,233 bp
DQ366329.1


(A/chicken/Guangxi/12/2004(H5N1)) PA protein
linear mRNA
GI:86753751


mRNA, complete cds




 23. Influenza A virus
1,565 bp
DQ366331.1


(A/chicken/Guangxi/12/2004(H5N1))
linear mRNA
GI:86753771


nucleocapsid mRNA, complete cds




 24. Influenza A virus
1,027 bp
DQ366333.1


(A/chicken/Guangxi/12/2004(H5N1)) matrix
linear mRNA
GI:86753791


protein mRNA, complete cds




 25. Influenza A virus (A/chicken/Hong
1,718 bp
AF057291.1


Kong/258/97(H5N1)) hemagglutinin mRNA,
linear mRNA
GI:3068720


complete cds




 26. Influenza A virus (A/chicken/Hong
1,318 bp
AF057292.1


Kong/258/97(H5N1)) neuraminidase mRNA,
linear mRNA
GI:3068722


partial cds




 27. Influenza A virus (A/chicken/Hong
1,508 bp
AF057293.1


Kong/258/97(H5N1)) nucleoprotein mRNA,
linear mRNA
GI:3068724


complete cds




 28. Influenza A virus (A/Chicken/Hong
1,726 bp
AF082034.1


Kong/728/97 (H5N1)) hemagglutinin H5 mRNA,
linear mRNA
GI:4240435


complete cds




 29. Influenza A virus (A/Chicken/Hong
1,726 bp
AF082035.1


Kong/786/97 (H5N1)) hemagglutinin H5 mRNA,
linear mRNA
GI:4240437


complete cds




 30. Influenza A virus (A/chicken/Hong
1,726 bp
AF082036.1


Kong/915/97(H5N1)) hemagglutinin H5 mRNA,
linear mRNA
GI:4240439


complete cds




 31. Influenza A virus (A/chicken/Hong
1,091 bp
AF082037.1


Kong/990/97 (H5N1)) hemagglutinin H5 mRNA,
linear mRNA
GI:4240441


partial cds




 32. Influenza A virus
1,002 bp
DQ676835.1


(A/chicken/Krasnodar/01/2006(H5N1)) matrix
linear mRNA
GI:108782521


protein 1 (M) mRNA, complete cds




 33. Influenza A virus
850 bp
DQ676837.1


(A/chicken/Krasnodar/01/2006(H5N1))
linear mRNA
GI:108782525


nonstructural protein (NS) mRNA, complete cds




 34. Influenza A virus
1,754 bp
DQ449632.1


(A/chicken/Kurgan/05/2005(H5N1))
linear mRNA
GI:90289625


hemagglutinin (HA) mRNA, complete cds




 35. Influenza A virus
1,002 bp
DQ449633.1


(A/chicken/Kurgan/05/2005(H5N1)) matrix
linear mRNA
GI:90289627


protein 1 (M) mRNA, complete cds




 36. Influenza A virus
1,373 bp
DQ449634.1


(A/chicken/Kurgan/05/2005(H5N1))
linear mRNA
GI:90289629


neuraminidase (NA) mRNA, complete cds




 37. Influenza A virus
1,540 bp
DQ449635.1


(A/chicken/Kurgan/05/2005(H5N1))
linear mRNA
GI:90289631


nucleoprotein (NP) mRNA, complete cds




 38. Influenza A virus
850 bp
DQ449636.1


(A/chicken/Kurgan/05/2005(H5N1))
linear mRNA
GI:90289633


nonstructural protein (NS) mRNA, complete cds




 39. Influenza A virus
2,208 bp
DQ449637.1


(A/chicken/Kurgan/05/2005(H5N1)) polymerase
linear mRNA
GI:90289635


acidic protein (PA) mRNA, complete cds




 40. Influenza A virus
2,316 bp
DQ449638.1


(A/chicken/Kurgan/05/2005(H5N1)) polymerase
linear mRNA
GI:90289637


basic protein 1 (PB1) mRNA, complete cds




 41. Influenza A virus
2,316 bp
DQ449639.1


(A/chicken/Kurgan/05/2005(H5N1)) polymerase
linear mRNA
GI:90289646


basic protein 2 (PB2) mRNA, complete cds




 42. Influenza A virus
184 bp
EU447276.1


(A/chicken/Lobzenko/01/2008(H5N1))
linear mRNA
GI:168998217


hemagglutinin (HA) mRNA, partial cds




 43. Influenza A virus
1,002 bp
DQ676831.1


(A/chicken/Mahachkala/05/2006(H5N1)) matrix
linear mRNA
GI:108782513


protein 1 (M) mRNA, complete cds




 44. Influenza A virus
850 bp
DQ676833.1


(A/chicken/Mahachkala/05/2006(H5N1))
linear mRNA
GI:108782517


nonstructural protein (NS) mRNA, complete cds




 45. Influenza A virus
1,531 bp
AM503030.1


(A/chicken/Nigeria/AB13/2006(H5N1)) mRNA for
linear mRNA
GI:147846296


nucleoprotein (np gene)




 46. Influenza A virus
827 bp
AM503040.1


(A/chicken/Nigeria/AB13/2006(H5N1)) mRNA for
linear mRNA
GI:147846316


non-structural protein (ns gene)




 47. Influenza A virus
2,169 bp
AM503051.1


(A/chicken/Nigeria/AB13/2006(H5N1)) partial
linear mRNA
GI:147846338


mRNA for polymerase (pa gene)




 48. Influenza A virus
2,259 bp
AM503060.1


(A/chicken/Nigeria/AB13/2006(H5N1)) partial
linear mRNA
GI:147846845


mRNA for polymerase basic protein 1 (pb1 gene)




 49. Influenza A virus
2,315 bp
AM503071.1


(A/chicken/Nigeria/AB13/2006(H5N1)) partial
linear mRNA
GI:147846867


mRNA for polymerase basic protein 2 (pb2 gene)




 70. Influenza A virus (A/chicken/Hong
1,055 bp
DQ250158.1


Kong/3123.1/2002(H5N1)) neuraminidase (NA)
linear mRNA
GI:82412012


mRNA, partial cds




 75. Influenza A virus
1,754 bp
DQ676834.1


(A/chicken/Krasnodar/01/2006(H5N1))
linear mRNA
GI:108782519


hemagglutinin (HA) mRNA, complete cds




 78. Influenza A virus
1,373 bp
DQ676836.2


(A/chicken/Krasnodar/01/2006(H5N1))
linear mRNA
GI:115520953


neuraminidase (NA) mRNA, complete cds




 91. Influenza A virus
184 bp
EU447276.1


(A/chicken/Lobzenko/01/2008(H5N1))
linear mRNA
GI:168998217


hemagglutinin (HA) mRNA, partial cds




 92. Influenza A virus
1,683 bp
DQ676830.1


(A/chicken/Mahachkala/05/2006(H5N1))
linear mRNA
GI:108782511


hemagglutinin (HA) mRNA, complete cds




 94. Influenza A virus
1,373 bp
DQ676832.1


(A/chicken/Mahachkala/05/2006(H5N1))
linear mRNA
GI:108782515


neuraminidase (NA) mRNA, complete cds




 96. Influenza A virus
433 bp
DQ096567.1


(A/chicken/Malaysia/01/2004(H5N1))
linear mRNA
GI:69145364


neuramidase (NA) mRNA, partial cds




 97. Influenza A virus
1,722 bp
AM503002.1


(A/chicken/Nigeria/AB13/2006(H5N1)) partial
linear mRNA
GI:147846240


mRNA for hemagglutinin (ha gene)




 98. Influenza A virus
1,329 bp
AM503020.1


(A/chicken/Nigeria/AB13/2006(H5N1)) partial
linear mRNA
GI:147846276


mRNA for neuraminidase (na gene)




105. Influenza A virus
1,719 bp
AM503003.1


(A/chicken/Nigeria/AB14/2006(H5N1)) partial
linear mRNA
GI:147846242


mRNA for hemagglutinin (ha gene)




106. Influenza A virus
953 bp
AM503011.1


(A/chicken/Nigeria/AB14/2006(H5N1)) partial
linear mRNA
GI:147846258


mRNA for matrix protein 1 (m1 gene)




107. Influenza A virus
1,343 bp
AM503025.1


(A/chicken/Nigeria/AB14/2006(H5N1)) partial
linear mRNA
GI:147846286


mRNA for neuraminidase (na gene)




108. Influenza A virus
827 bp
AM503041.1


(A/chicken/Nigeria/AB14/2006(H5N1)) mRNA for
linear mRNA
GI:147846318


non-structural protein (ns gene)




109. Influenza A virus
2,169 bp
AM503054.1


(A/chicken/Nigeria/AB14/2006(H5N1)) partial
linear mRNA
GI:147846344


mRNA for polymerase (pa gene)




110. Influenza A virus
2,259 bp
AM503061.1


(A/chicken/Nigeria/AB14/2006(H5N1)) partial
linear mRNA
GI:147846847


mRNA for polymerase basic protein 1 (pb1 gene)




111. Influenza A virus
2,315 bp
AM503072.1


(A/chicken/Nigeria/AB14/2006(H5N1)) partial
linear mRNA
GI:147846869


mRNA for polymerase basic protein 2 (pb2 gene)




112. Influenza A virus
1,548 bp
AM503034.2


(A/chicken/Nigeria/AB14/2006(H5N1)) mRNA for
linear mRNA
GI:149773117


nucleoprotein (np gene)




113. Influenza A virus
1,342 bp
AM503022.1


(A/chicken/Nigeria/BA210/2006(H5N1)) partial
linear mRNA
GI:147846280


mRNA for neuraminidase (na gene)




114. Influenza A virus
1,321 bp
AM503021.1


(A/chicken/Nigeria/BA211/2006(H5N1)) partial
linear mRNA
GI:147846278


mRNA for neuraminidase (na gene)




115. Influenza A virus
2,315 bp
AM503073.1


(A/chicken/Nigeria/BA211/2006(H5N1)) partial
linear mRNA
GI:147846871


mRNA for polymerase basic protein 2 (pb2 gene)




116. Influenza A virus
1,717 bp
AM503004.1


(A/chicken/Nigeria/FA4/2006(H5N1)) partial
linear mRNA
GI:147846244


mRNA for hemagglutinin (ha gene)




117. Influenza A virus
989 bp
AM503013.1


(A/chicken/Nigeria/FA4/2006(H5N1)) partial
linear mRNA
GI:147846262


mRNA for matrix protein 1 (m1 gene)




118. Influenza A virus
1,321 bp
AM503026.1


(A/chicken/Nigeria/FA4/2006(H5N1)) partial
linear mRNA
GI:147846288


mRNA for neuraminidase (na gene)




119. Influenza A virus
827 bp
AM503045.1


(A/chicken/Nigeria/FA4/2006(H5N1)) mRNA for
linear mRNA
GI:147846326


non-structural protein (ns gene)




120. Influenza A virus
2,169 bp
AM503055.1


(A/chicken/Nigeria/FA4/2006(H5N1)) partial
linear mRNA
GI:147846346


mRNA for polymerase (pa gene)




121. Influenza A virus
2,259 bp
AM503064.1


(A/chicken/Nigeria/FA4/2006(H5N1)) partial
linear mRNA
GI:147846853


mRNA for polymerase basic protein 1 (pb1 gene)




122. Influenza A virus
2,224 bp
AM503074.1


(A/chicken/Nigeria/FA4/2006(H5N1)) partial
linear mRNA
GI:147846873


mRNA for polymerase basic protein 2 (pb2 gene)




123. Influenza A virus
1,717 bp
AM502998.1


(A/chicken/Nigeria/FA6/2006(H5N1)) partial
linear mRNA
GI:147846232


mRNA for hemagglutinin (ha gene)




124. Influenza A virus
965 bp
AM503012.1


(A/chicken/Nigeria/FA6/2006(H5N1)) partial
linear mRNA
GI:147846260


mRNA for matrix protein 1 (m1 gene)




125. Influenza A virus
1,327 bp
AM503023.1


(A/chicken/Nigeria/FA6/2006(H5N1)) partial
linear mRNA
GI:147846282


mRNA for neuraminidase (na gene)




126. Influenza A virus
1,543 bp
AM503031.1


(A/chicken/Nigeria/FA6/2006(H5N1)) mRNA for
linear mRNA
GI:147846298


nucleoprotein (np gene)




127. Influenza A virus
2,169 bp
AM503052.1


(A/chicken/Nigeria/FA6/2006(H5N1)) partial
linear mRNA
GI:147846340


mRNA for polymerase (pa gene)




128. Influenza A virus
2,259 bp
AM503063.1


(A/chicken/Nigeria/FA6/2006(H5N1)) partial
linear mRNA
GI:147846851


mRNA for polymerase basic protein 1 (pb1 gene)




129. Influenza A virus
1,710 bp
AM502999.1


(A/chicken/Nigeria/FA7/2006(H5N1)) partial
linear mRNA
GI:147846234


mRNA for hemagglutinin (ha gene)




130. Influenza A virus
1,001 bp
AM503009.1


(A/chicken/Nigeria/FA7/2006(H5N1)) partial
linear mRNA
GI:147846254


mRNA for matrix protein 1 (m1 gene)




131. Influenza A virus
1,331 bp
AM503018.1


(A/chicken/Nigeria/FA7/2006(H5N1)) partial
linear mRNA
GI:147846272


mRNA for neuraminidase (na gene)




132. Influenza A virus
1,531 bp
AM503035.1


(A/chicken/Nigeria/FA7/2006(H5N1)) mRNA for
linear mRNA
GI:147846306


nucleoprotein (np gene)




133. Influenza A virus
827 bp
AM503042.1


(A/chicken/Nigeria/FA7/2006(H5N1)) mRNA for
linear mRNA
GI:147846320


non-structural protein (ns gene)




134. Influenza A virus
2,169 bp
AM503049.1


(A/chicken/Nigeria/FA7/2006(H5N1)) partial
linear mRNA
GI:147846334


mRNA for polymerase (pa gene)




135. Influenza A virus
2,259 bp
AM503057.1


(A/chicken/Nigeria/FA7/2006(H5N1)) partial
linear mRNA
GI:147846350


raRNA for polymerase basic protein 1 (pb1 gene)




136. Influenza A virus
2,315 bp
AM503068.1


(A/chicken/Nigeria/FA7/2006(H5N1)) partial
linear mRNA
GI:147846861


mRNA for polymerase basic protein 2 (pb2 gene)




137. Influenza A virus
1,714 bp
AM503001.1


(A/chicken/Nigeria/IF10/2006(H5N1)) partial
linear mRNA
GI:147846238


mRNA for hemagglutinin (ha gene)




138. Influenza A virus
990 bp
AM503010.1


(A/chicken/Nigeria/IF10/2006(H5N1)) partial
linear mRNA
GI:147846256


mRNA for matrix protein 1 (m1 gene)




139. Influenza A virus
1,332 bp
AM503024.1


(A/chicken/Nigeria/IF10/2006(H5N1)) partial
linear mRNA
GI:147846284


mRNA for neuraminidase (na gene)




140. Influenza A virus
827 bp
AM503044.1


(A/chicken/Nigeria/IF10/2006(H5N1)) mRNA for
linear mRNA
GI:147846324


non-structural protein (ns gene)




141. Influenza A virus
2,169 bp
AM503053.1


(A/chicken/Nigeria/IF10/2006(H5N1)) partial
linear mRNA
GI:147846342


mRNA for polymerase (pa gene)




142. Influenza A virus
2,259 bp
AM503059.1


(A/chicken/Nigeria/IF10/2006(H5N1)) partial
linear mRNA
GI:147846843


mRNA for polymerase basic protein 1 (pb1 gene)




143. Influenza A virus
2,315 bp
AM503069.1


(A/chicken/Nigeria/IF10/2006(H5N1)) partial
linear mRNA
GI:147846863


mRNA for polymerase basic protein 2 (pb2 gene)




144. Influenza A virus
1,550 bp
AM503033.2


(A/chicken/Nigeria/IF10/2006(H5N1)) mRNA for
linear mRNA
GI:149773115


nucleoprotein (np gene)




145. Influenza A virus
1,719 bp
AM503005.1


(A/chicken/Nigeria/OD8/2006(H5N1)) partial
linear mRNA
GI:147846246


mRNA for hemagglutinin (ha gene)




146. Influenza A virus
989 bp
AM503014.1


(A/chicken/Nigeria/OD8/2006(H5N1)) partial
linear mRNA
GI:147846264


mRNA for matrix protein 1 (m1 gene)




147. Influenza A virus
1,720 bp
AM503000.1


(A/chicken/Nigeria/OD9/2006(H5N1)) partial
linear mRNA
GI:147846236


mRNA for hemagglutinin (ha gene)




148. Influenza A virus
988 bp
AM503015.1


(A/chicken/Nigeria/OD9/2006(H5N1)) partial
linear mRNA
GI:147846266


mRNA for matrix protein 1 (m1 gene)




149. Influenza A virus
1,330 bp
AM503019.1


(A/chicken/Nigeria/OD9/2006(H5N1)) partial
linear mRNA
GI:147846274


mRNA for neuraminidase (na gene)




150. Influenza A virus
1,531 bp
AM503032.1


(A/chicken/Nigeria/OD9/2006(H5N1)) mRNA for
linear mRNA
GI:147846300


nucleoprotein (np gene)




151. Influenza A virus
827 bp
AM503043.1


(A/chicken/Nigeria/OD9/2006(H5N1)) mRNA for
linear mRNA
GI:147846322


non-structural protein (ns gene)




152. Influenza A virus
2,169 bp
AM503050.1


(A/chicken/Nigeria/OD9/2006(H5N1)) partial
linear mRNA
GI:147846336


mRNA for polymerase (pa gene)




153. Influenza A virus
2,259 bp
AM503058.1


(A/chicken/Nigeria/OD9/2006(H5N1)) partial
linear mRNA
GI:147846841


raRNA for polymerase basic protein 1 (pb1 gene)




154. Influenza A virus
2,315 bp
AM503070.1


(A/chicken/Nigeria/OD9/2006(H5N1)) partial
linear mRNA
GI:147846865


mRNA for polymerase basic protein 2 (pb2 gene)




155. Influenza A virus
1,768 bp
X07869.1


(A/chicken/Scotland/59(H5N1)) mRNA for
linear mRNA
GI:60482


haemaggiutinin precursor




156. Influenza A virus
1,445 bp
AJ416625.1


(A/chicken/Scotland/59(H5N1)) N1 gene for
linear mRNA
GI:39840717


neuraminidase, genomic RNA




161. Influenza A virus
1,497 bp
DQ208502.1


(A/chicken/zz/02/2004(H5N1)) nucleoprotein
linear mRNA
GI:77158587


mRNA, complete cds




162. Influenza A virus (A/common
1,707 bp
EF110519.1


coot/Switzerland/V544/2006(H5N1))
linear mRNA
GI:119394676


hemagglutinin (HA) gene, complete cds




163. Influenza A virus (A/domestic
1,735 bp
EU190482.1


goose/Pavlodar/1/2005(H5N1)) hemagglutinin
linear mRNA
GI:158516739


(HA) mRNA, complete cds




164. Influenza A virus (A/duck/Eastern
1,401 bp
EU429750.1


China/145/2003(H5N1)) segment 6
linear mRNA
GI:167859465


neuraminidase (NA) mRNA, complete cds




165. Influenza A virus (A/duck/Eastern
1,407 bp
EU429731.1


China/150/2003(H5N1)) segment 6
linear mRNA
GI:167859427


neuraminidase (NA) mRNA, complete cds




166. Influenza A virus (A/duck/Eastern
1,398 bp
EU429783.1


China/22/2005(H5N1)) segment 6 neuraminidase
linear mRNA
GI:167859531


(NA) mRNA, complete cds




167. Influenza A virus (A/duck/Eastern
1,398 bp
EU429747.1


China/304/2002(H5N1)) segment 6
linear mRNA
GI:167859459


neuraminidase (NA) mRNA, complete cds




168. Influenza A virus (A/duck/Eastern
1,401 bp
EU429727.1


China/318/2002(H5N1)) segment 6
linear mRNA
GI:167859419


neuraminidase (NA) mRNA, complete cds




169. Influenza A virus (A/duck/Eastern
1,399 bp
EU429778.1


China/37/2006(H5N1)) segment 6 neuraminidase
linear mRNA
GI:167859521


(NA) mRNA, complete cds




170. Influenza A virus (A/duck/Eastern
1,398 bp
EU429757.1


China/40/2005(H5N1)) segment 6 neuraminidase
linear mRNA
GI:167859479


(NA) mRNA, complete cds




171. Influenza A virus (A/duck/Eastern
1,398 bp
EU429779.1


China/48/2006(H5N1)) segment 6 neuraminidase
linear mRNA
GI:167859523


(NA) mRNA, complete cds




172. Influenza A virus (A/duck/Eastern
1,398 bp
EU429763.1


China/51/2005(H5N1)) segment 6 neuraminidase
linear mRNA
GI:167859491


(NA) mRNA, complete cds




173. Influenza A virus (A/duck/Eastern
1,398 bp
EU429758.1


China/54/2005(H5N1)) segment 6 neuraminidase
linear mRNA
GI:167859481


(NA) mRNA, complete cds




174. Influenza A virus (A/duck/Eastern
1,398 bp
EU429764.1


China/58/2005(H5N1)) segment 6 neuraminidase
linear mRNA
GI:167859493


(NA) mRNA, complete cds




175. Influenza A virus (A/duck/Eastern
1,398 bp
EU429759.1


China/59/2005(H5N1)) segment 6 neuraminidase
linear mRNA
GI:167859483


(NA) mRNA, complete cds




176. Influenza A virus (A/duck/Eastern
1,398 bp
EU429765.1


China/89/2005(H5N1)) segment 6 neuraminidase
linear mRNA
GI:167859495


(NA) mRNA, complete cds




177. Influenza A virus (A/duck/Eastern
1,399 bp
EU429785.1


China/89/2006(H5N1)) segment 6 neuraminidase
linear mRNA
GI:167859535


(NA) mRNA, complete cds




178. Influenza A virus (A/duck/Eastern
1,398 bp
EU429717.1


China/97/2001(H5N1)) segment 6 neuraminidase
linear mRNA
GI:167859399


(NA) mRNA, complete cds




179. Influenza A virus
2,281 bp
AY585504.1


(A/duck/Fujian/01/2002(H5N1)) polymerase
linear mRNA
GI:47156226


basic protein 2 (PB2) mRNA, complete cds




180. Influenza A virus
760 bp
AY585378.1


(A/duck/Fujian/01/2002(H5N1)) matrix protein
linear mRNA
GI:47156310


mRNA, complete cds




181. Influenza A virus
1,357 bp
AY585399.1


(A/duck/Fujian/01/2002(H5N1)) neuraminidase
linear mRNA
GI:47156352


(NA) mRNA, complete cds




182. Influenza A virus
1,497 bp
AY585420.1


(A/duck/Fujian/01/2002(H5N1)) nucleoprotein
linear mRNA
GI:47156394


(NP) mRNA, complete cds




183. Influenza A virus
686 bp
AY585441.1


(A/duck/Fujian/01/2002(H5N1)) nonstructural
linear mRNA
GI:47156436


protein 1 (NS1) mRNA, partial cds




184. Influenza A virus
2,281 bp
AY585505.1


(A/duck/Fujian/13/2002(H5N1)) polymerase
linear mRNA
GI:47156228


basic protein 2 (PB2) mRNA, complete cds




185. Influenza A virus
761 bp
AY585379.1


(A/duck/Fujian/13/2002(H5N1)) matrix protein
linear mRNA
GI:47156312


mRNA, complete cds




186. Influenza A virus
1,357 bp
AY585400.1


(A/duck/Fujian/13/2002(H5N1)) neuraminidase
linear mRNA
GI:47156354


(NA) mRNA, complete cds




187. Influenza A virus
1,499 bp
AY585421.1


(A/duck/Fujian/13/2002(H5N1)) nucleoprotein
linear mRNA
GI:47156396


(NP) mRNA, complete cds




188. Influenza A virus
685 bp
AY585442.1


(A/duck/Fujian/13/2002(H5N1)) nonstructural
linear mRNA
GI:47156438


protein 1 (NS1) mRNA, partial cds




189. Influenza A virus
2,281 bp
AY585506.1


(A/duck/Fujian/17/2001(H5N1)) polymerase
linear mRNA
GI:47156230


basic protein 2 (PB2) mRNA, complete cds




190. Influenza A virus
759 bp
AY585380.1


(A/duck/Fujian/17/2001(H5N1)) matrix protein
linear mRNA
GI:47156314


mRNA, complete cds




191. Influenza A virus
1,418 bp
AY585401.1


(A/duck/Fujian/17/2001(H5N1)) neuraminidase
linear mRNA
GI:47156356


(NA) mRNA, complete cds




192. Influenza A virus
1,498 bp
AY585422.1


(A/duck/Fujian/17/2001(H5N1)) nucleoprotein
linear mRNA
GI:47156398


(NP) mRNA, complete cds




193. Influenza A virus
686 bp
AY585443.1


(A/duck/Fujian/17/2001(H5N1)) nonstructural
linear mRNA
GI:47156440


protein 1 (NS1) mRNA, complete cds




194. Influenza A virus
2,281 bp
AY585507.1


(A/duck/Fujian/19/2000(H5N1)) polymerase
linear mRNA
GI:47156232


basic protein 2 (PB2) mRNA, complete cds




195. Influenza A virus
760 bp
AY585381.1


(A/duck/Fujian/19/2000(H5N1)) matrix protein
linear mRNA
GI:47156316


mRNA, complete cds




196. Influenza A virus
1,355 bp
AY585402.1


(A/duck/Fujian/19/2000(H5N1)) neuraminidase
linear mRNA
GI:47156358


(NA) mRNA, complete cds




197. Influenza A virus
1,498 bp
AY585423.1


(A/duck/Fujian/19/2000(H5N1)) nucleoprotein
linear mRNA
GI:47156400


(NP) mRNA, complete cds




198. Influenza A virus
687 bp
AY585444.1


(A/duck/Fujian/19/2000(H5N1)) nonstructural
linear mRNA
GI:47156442


protein 1 (NS1) mRNA, complete cds




199. Influenza A virus
2,281 bp
AY585508.1


(A/duck/Guangdong/01/2001(H5N1)) polymerase
linear mRNA
GI:47156234


basic protein 2 (PB2) mRNA, complete cds




200. Influenza A virus
760 bp
AY585382.1


(A/duck/Guangdong/01/2001(H5N1)) matrix
linear mRNA
GI:47156318


protein mRNA, complete cds




201. Influenza A virus
1,414 bp
AY585403.1


(A/duck/Guangdong/01/2001(H5N1))
linear mRNA
GI:47156360


neuraminidase (NA) mRNA, complete cds




202. Influenza A virus
1,497 bp
AY585424.1


(A/duck/Guangdong/01/2001(H5N1))
linear mRNA
GI:47156402


nucleoprotein (NP) mRNA, complete cds




203. Influenza A virus
687 bp
AY585445.1


(A/duck/Guangdong/01/2001(H5N1))
linear mRNA
GI:47156444


nonstructural protein 1 (NS1) mRNA, complete cds




204. Influenza A virus
2,280 bp
AY585509.1


(A/duck/Guangdong/07/2000(H5N1)) polymerase
linear mRNA
GI:47156236


basic protein 2 (PB2) mRNA, complete cds




205. Influenza A virus
759 bp
AY585383.1


(A/duck/Guangdong/07/2000(H5N1)) matrix
linear mRNA
GI:47156320


protein mRNA, complete cds




206. Influenza A virus
1,417 bp
AY585404.1


(A/duck/Guangdong/07/2000(H5N1))
linear mRNA
GI:47156362


neuraminidase (NA) mRNA, complete cds




207. Influenza A virus
1,497 bp
AY585425.1


(A/duck/Guangdong/07/2000(H5N1))
linear mRNA
GI:47156404


nucleoprotein (NP) mRNA, complete cds




208. Influenza A virus
690 bp
AY585446.1


(A/duck/Guangdong/07/2000(H5N1))
linear mRNA
GI:47156446


nonstructural protein 1 (NS1) mRNA, partial cds




209. Influenza A virus
2,281 bp
AY585510.1


(A/duck/Guangdong/12/2000(H5N1)) polymerase
linear mRNA
GI:47156238


basic protein 2 (PB2) mRNA, complete cds




210. Influenza A virus
760 bp
AY585384.1


(A/duck/Guangdong/12/2000(H5N1)) matrix
linear mRNA
GI:47156322


protein mRNA, complete cds




211. Influenza A virus
1,359 bp
AY585405.1


(A/duck/Guangdong/12/2000(H5N1))
linear mRNA
GI:47156364


neuraminidase (NA) mRNA, complete cds




212. Influenza A virus
1,498 bp
AY585426.1


(A/duck/Guangdong/12/2000(H5N1))
linear mRNA
GI:47156406


nucleoprotein (NP) mRNA, complete cds




213. Influenza A virus
685 bp
AY585447.1


(A/duck/Guangdong/12/2000(H5N1))
linear mRNA
GI:47156448


nonstructural protein 1 (NS1) mRNA, partial cds




214. Influenza A virus
2,281 bp
AY585511.1


(A/duck/Guangdong/22/2002(H5N1)) polymerase
linear mRNA
GI:47156240


basic protein 2 (PB2) mRNA, complete cds




215. Influenza A virus
760 bp
AY585385.1


(A/duck/Guangdong/22/2002(H5N1)) matrix
linear mRNA
GI:47156324


protein mRNA, complete cds




216. Influenza A virus
1,412 bp
AY585406.1


(A/duck/Guangdong/22/2002(H5N1))
linear mRNA
GI:47156366


neuraminidase (NA) mRNA, complete cds




217. Influenza A virus
1,499 bp
AY585427.1


(A/duck/Guangdong/22/2002(H5N1))
linear mRNA
GI:47156408


nucleoprotein (NP) mRNA, complete cds




218. Influenza A virus
682 bp
AY585448.1


(A/duck/Guangdong/22/2002(H5N1))
linear mRNA
GI:47156450


nonstructural protein 1 (NS1) mRNA, complete cds




219. Influenza A virus
2,281 bp
AY585512.1


(A/duck/Guangdong/40/2000(H5N1)) polymerase
linear mRNA
GI:47156242


basic protein 2 (PB2) mRNA, complete cds




220. Influenza A virus
760 bp
AY585386.1


(A/duck/Guangdong/40/2000(H5N1)) matrix
linear mRNA
GI:47156326


protein mRNA, complete cds




221. Influenza A virus
1,401 bp
AY585407.1


(A/duck/Guangdong/40/2000(H5N1))
linear mRNA
GI:47156368


neuraminidase (NA) mRNA, partial cds




222. Influenza A virus
1,499 bp
AY585428.1


(A/duck/Guangdong/40/2000(H5N1))
linear mRNA
GI:47156410


nucleoprotein (NP) mRNA, complete cds




223. Influenza A virus
689 bp
AY585449.1


(A/duck/Guangdong/40/2000(H5N1))
linear mRNA
GI:47156452


nonstructural protein 1 (NS1) mRNA, partial cds




224. Influenza A virus
2,281 bp
AY585513.1


(A/duck/Guangxi/07/1999(H5N1)) polymerase
linear mRNA
GI:47156244


basic protein 2 (PB2) mRNA, complete cds




225. Influenza A virus
760 bp
AY585387.1


(A/duck/Guangxi/07/1999(H5N1)) matrix
linear mRNA
GI:47156328


protein mRNA, complete cds




226. Influenza A virus
1,421 bp
AY585408.1


(A/duck/Guangxi/07/1999(H5N1)) neuraminidase
linear mRNA
GI:47156370


(NA) mRNA, complete cds




227. Influenza A virus
1,501 bp
AY585429.1


(A/duck/Guangxi/07/1999(H5N1)) nucleoprotein
linear mRNA
GI:47156412


(NP) mRNA, complete cds




228. Influenza A virus
687 bp
AY585450.1


(A/duck/Guangxi/07/1999(H5N1)) nonstructural
linear mRNA
GI:47156454


protein 1 (NS1) mRNA, partial cds




229. Influenza A virus
875 bp
DQ366342.1


(A/duck/Guangxi/13/2004(H5N1)) nonstructural
linear mRNA
GI:86753723


protein 1 mRNA, complete cds




230. Influenza A virus
2,341 bp
DQ366335.1


(A/duck/Guangxi/13/2004(H5N1)) polymerase
linear mRNA
GI:86753733


PB2 mRNA, complete cds




231. Influenza A virus
2,341 bp
DQ366336.1


(A/duck/Guangxi/13/2004(H5N1)) polymerase
linear mRNA
GI:86753743


PB1 mRNA, complete cds




232. Influenza A virus
2,233 bp
DQ366337.1


(A/duck/Guangxi/13/2004(H5N1)) PA protein
linear mRNA
GI:86753753


mRNA, complete cds




233. Influenza A virus
1,776 bp
DQ366338.1


(A/duck/Guangxi/13/2004(H5N1)) hemagglutinin
linear mRNA
GI:86753763


mRNA, complete cds




234. Influenza A virus
1,565 bp
DQ366339.1


(A/duck/Guangxi/13/2004(H5N1)) nucleocapsid
linear mRNA
GI:86753773


mRNA, complete cds




235. Influenza A virus
1,378 bp
DQ366340.1


(A/duck/Guangxi/13/2004(H5N1)) neuraminidase
linear mRNA
GI:86753783


mRNA, complete cds




236. Influenza A virus
1,027 bp
DQ366341.1


(A/duck/Guangxi/13/2004(H5N1)) matrix
linear mRNA
GI:86753793


protein mRNA, complete cds




237. Influenza A virus
2,281 bp
AY585514.1


(A/duck/Guangxi/22/2001(H5N1)) polymerase
linear mRNA
GI:47156246


basic protein 2 (PB2) mRNA, complete cds




238. Influenza A virus
757 bp
AY585388.1


(A/duck/Guangxi/22/2001(H5N1)) matrix
linear mRNA
GI:47156330


protein mRNA, partial cds




239. Influenza A virus
1,414 bp
AY585409.1


(A/duck/Guangxi/22/2001(H5N1)) neuraminidase
linear mRNA
GI:47156372


(NA) mRNA, complete cds




240. Influenza A virus
1,498 bp
AY585430.1


(A/duck/Guangxi/22/2001(H5N1)) nucleoprotein
linear mRNA
GI:47156414


(NP) mRNA, complete cds




241. Influenza A virus
687 bp
AY585451.1


(A/duck/Guangxi/22/2001(H5N1)) nonstructural
linear mRNA
GI:47156456


protein 1 (NS1) mRNA, complete cds




242. Influenza A virus
2,281 bp
AY585515.1


(A/duck/Guangxi/35/2001(H5N1)) polymerase
linear mRNA
GI:47156248


basic protein 2 (PB2) mRNA, complete cds




243. Influenza A virus
760 bp
AY585389.1


(A/duck/Guangxi/35/2001(H5N1)) matrix
linear mRNA
GI:47156332


protein mRNA, complete cds




244. Influenza A virus
1,414 bp
AY585410.1


(A/duck/Guangxi/35/2001(H5N1)) neuraminidase
linear mRNA
GI:47156374


(NA) mRNA, complete cds




245. Influenza A virus
1,498 bp
AY585431.1


(A/duck/Guangxi/35/2001(H5N1)) nucleoprotein
linear mRNA
GI:47156416


(NP) mRNA, complete cds




246. Influenza A virus
685 bp
AY585452.1


(A/duck/Guangxi/35/2001(H5N1)) nonstructural
linear mRNA
GI:47156458


protein 1 (NS1) mRNA, complete cds




247. Influenza A virus
2,281 bp
AY585516.1


(A/duck/Guangxi/50/2001(H5N1)) polymerase
linear mRNA
GI:47156250


basic protein 2 (PB2) mRNA, complete cds




248. Influenza A virus
760 bp
AY585398.1


(A/duck/Guangxi/50/2001(H5N1)) matrix
linear mRNA
GI:47156350


protein mRNA, complete cds




249. Influenza A virus
1,354 bp
AY585411.1


(A/duck/Guangxi/50/2001(H5N1)) neuraminidase
linear mRNA
GI:47156376


(NA) mRNA, complete cds




250. Influenza A virus
1,498 bp
AY585432.1


(A/duck/Guangxi/50/2001(H5N1)) nucleoprotein
linear mRNA
GI:47156418


(NP) mRNA, complete cds




251. Influenza A virus
686 bp
AY585453.1


(A/duck/Guangxi/50/2001(H5N1)) nonstructural
linear mRNA
GI:47156460


protein 1 (NS1) mRNA, complete cds




252. Influenza A virus
2,281 bp
AY585517.1


(A/duck/Guangxi/53/2002(H5N1)) polymerase
linear mRNA
GI:47156252


basic protein 2 (PB2) mRNA, complete cds




253. Influenza A virus
760 bp
AY585390.1


(A/duck/Guangxi/53/2002(H5N1)) matrix
linear mRNA
GI:47156334


protein mRNA, complete cds




254. Influenza A virus
1,361 bp
AY585412.1


(A/duck/Guangxi/53/2002(H5N1)) neuraminidase
linear mRNA
GI:47156378


(NA) mRNA, complete cds




255. Influenza A virus
1,498 bp
AY585433.1


(A/duck/Guangxi/53/2002(H5N1)) nucleoprotein
linear mRNA
GI:47156420


(NP) mRNA, complete cds




256. Influenza A virus
687 bp
AY585454.1


(A/duck/Guangxi/53/2002(H5N1)) nonstructural
linear mRNA
GI:47156462


protein 1 (NS1) mRNA, partial cds




257. Influenza A virus
1,754 bp
DQ449640.1


(A/duck/Kurgan/08/2005(H5N1)) hemagglutinin
linear mRNA
GI:90289674


(HA) mRNA, complete cds




258. Influenza A virus
1,002 bp
DQ449641.1


(A/duck/Kurgan/08/2005(H5N1)) matrix protein
linear mRNA
GI:90289689


1 (M) mRNA, complete cds




259. Influenza A virus
1,373 bp
DQ449642.1


(A/duck/Kurgan/08/2005(H5N1)) neuraminidase
linear mRNA
GI:90289708


(NA) mRNA, complete cds




260. Influenza A virus
1,540 bp
DQ449643.1


(A/duck/Kurgan/08/2005(H5N1)) nucleoprotein
linear mRNA
GI:90289731


(NP) mRNA, complete cds




261. Influenza A virus
850 bp
DQ449644.1


(A/duck/Kurgan/08/2005(H5N1)) nonstructural
linear mRNA
GI:90289739


protein (NS) mRNA, complete cds




262. Influenza A virus
2,208 bp
DQ449645.1


(A/duck/Kurgan/08/2005(H5N1)) polymerase
linear mRNA
GI:90289756


acidic protein (PA) mRNA, complete cds




263. Influenza A virus
2,316 bp
DQ449646.1


(A/duck/Kurgan/08/2005(H5N1)) polymerase
linear mRNA
GI:90289774


basic protein 1 (PB1) mRNA, complete cds




264. Influenza A virus
2,316 bp
DQ449647.1


(A/duck/Kurgan/08/2005(H5N1)) polymerase
linear mRNA
GI:90289783


basic protein 2 (PB2) mRNA, complete cds




266. Influenza A virus
2,281 bp
AY585518.1


(A/duck/Shanghai/08/2001(H5N1)) polymerase
linear mRNA
GI:47156254


basic protein 2 (PB2) mRNA, complete cds




267. Influenza A virus
760 bp
AY585391.1


(A/duck/Shanghai/08/2001(H5N1)) matrix
linear mRNA
GI:47156336


protein mRNA, complete cds




268. Influenza A virus
1,357 bp
AY585413.1


(A/duck/Shanghai/08/2001(H5N1))
linear mRNA
GI:47156380


neuraminidase (NA) mRNA, complete cds




269. Influenza A virus
1,498 bp
AY585434.1


(A/duck/Shanghai/08/2001(H5N1))
linear mRNA
GI:47156422


nucleoprotein (NP) mRNA, complete cds




270. Influenza A virus
685 bp
AY585455.1


(A/duck/Shanghai/08/2001(H5N1))
linear mRNA
GI:47156464


nonstructural protein 1 (NS1) mRNA, partial cds




271. Influenza A virus
2,281 bp
AY585519.1


(A/duck/Shanghai/13/2001(H5N1)) polymerase
linear mRNA
GI:47156256


basic protein 2 (PB2) mRNA, complete cds




272. Influenza A virus
760 bp
AY585392.1


(A/duck/Shanghai/13/2001(H5N1)) matrix
linear mRNA
GI:47156338


protein mRNA, complete cds




273. Influenza A virus
1,417 bp
AY585414.1


(A/duck/Shanghai/13/2001(H5N1))
linear mRNA
GI:47156382


neuraminidase (NA) mRNA, complete cds




274. Influenza A virus
1,499 bp
AY585435.1


(A/duck/Shanghai/13/2001(H5N1))
linear mRNA
GI:47156424


nucleoprotein (NP) mRNA, complete cds




275. Influenza A virus
685 bp
AY585456.1


(A/duck/Shanghai/13/2001(H5N1))
linear mRNA
GI:47156466


nonstructural protein 1 (NS1) mRNA, complete cds




276. Influenza A virus
2,281 bp
AY585520.1


(A/duck/Shanghai/35/2002(H5N1)) polymerase
linear mRNA
GI:47156258


basic protein 2 (PB2) mRNA, complete cds




277. Influenza A virus
760 bp
AY585393.1


(A/duck/Shanghai/35/2002(H5N1)) matrix
linear mRNA
GI:47156340


protein mRNA, complete cds




278. Influenza A virus
1,363 bp
AY585415.1


(A/duck/Shanghai/35/2002(H5N1))
linear mRNA
GI:47156384


neuraminidase (NA) mRNA, complete cds




279. Influenza A virus
1,498 bp
AY585436.1


(A/duck/Shanghai/35/2002(H5N1))
linear mRNA
GI:47156426


nucleoprotein (NP) mRNA, complete cds




280. Influenza A virus
685 bp
AY585457.1


(A/duck/Shanghai/35/2002(H5N1))
linear mRNA
GI:47156468


nonstructural protein 1 (NS1) mRNA, partial cds




281. Influenza A virus
2,281 bp
AY585521.1


(A/duck/Shanghai/37/2002(H5N1)) polymerase
linear mRNA
GI:47156260


basic protein 2 (PB2) mRNA, complete cds




282. Influenza A virus
760 bp
AY585394.1


(A/duck/Shanghai/37/2002(H5N1)) matrix
linear mRNA
GI:47156342


protein mRNA, complete cds




283. Influenza A virus
1,361 bp
AY585416.1


(A/duck/Shanghai/37/2002(H5N1))
linear mRNA
GI:47156386


neuraminidase (NA) mRNA, complete cds




284. Influenza A virus
1,497 bp
AY585437.1


(A/duck/Shanghai/37/2002(H5N1))
linear mRNA
GI:47156428


nucleoprotein (NP) mRNA, complete cds




285. Influenza A virus
685 bp
AY585458.1


(A/duck/Shanghai/37/2002(H5N1))
linear mRNA
GI:47156470


nonstructural protein 1 (NS1) mRNA, partial cds




286. Influenza A virus
2,282 bp
AY585522.1


(A/duck/Shanghai/38/2001(H5N1)) polymerase
linear mRNA
GI:47156262


basic protein 2 (PB2) mRNA, complete cds




287. Influenza A virus
760 bp
AY585395.1


(A/duck/Shanghai/38/2001(H5N1)) matrix
linear mRNA
GI:47156344


protein mRNA, complete cds




288. Influenza A virus
1,355 bp
AY585417.1


(A/duck/Shanghai/38/2001(H5N1))
linear mRNA
GI:47156388


neuraminidase (NA) mRNA, complete cds




289. Influenza A virus
1,499 bp
AY585438.1


(A/duck/Shanghai/38/2001(H5N1))
linear mRNA
GI:47156430


nucleoprotein (NP) mRNA, complete cds




290. Influenza A virus
692 bp
AY585459.1


(A/duck/Shanghai/38/2001(H5N1))
linear mRNA
GI:47156472


nonstructural protein 1 (NS1) mRNA, partial cds




291. Influenza A virus
875 bp
DQ354059.1


(A/duck/Sheyang/1/2005(H5N1)) nonstructural
linear mRNA
GI:87128643


protein (NS) mRNA, complete cds




292. Influenza A virus
1,748 bp
DQ861291.1


(A/duck/Tuva/01/2006(H5N1)) hemagglutinin
linear mRNA
GI:112820195


(HA) mRNA, complete cds




293. Influenza A virus
991 bp
DQ861292.1


(A/duck/Tuva/01/2006(H5N1)) matrix protein 1
linear mRNA
GI:112820197


(M1) mRNA, complete cds




294. Influenza A virus
1,364 bp
DQ861293.1


(A/duck/Tuva/01/2006(H5N1)) neuraminidase
linear mRNA
GI:112820199


(NA) mRNA, complete cds




295. Influenza A virus
1,531 bp
DQ861294.1


(A/duck/Tuva/01/2006(H5N1)) nucleoprotein
linear mRNA
GI:112820201


(NP) mRNA, complete cds




296. Influenza A virus
842 bp
DQ861295.1


(A/duck/Tuva/01/2006(H5N1)) nonstructural
linear mRNA
GI:112820203


protein (NS) mRNA, complete cds




297. Influenza A virus
890 bp
DQ366310.1


(A/duck/Vietnam/1/2005(H5N1)) nonstructural
linear mRNA
GI:86753715


protein 1 mRNA, complete cds




298. Influenza A virus
2,341 bp
DQ366303.1


(A/duck/Vietnam/1/2005(H5N1)) polymerase PB2
linear mRNA
GI:86753725


mRNA, complete cds




299. Influenza A virus
2,341 bp
DQ366304.1


(A/duck/Vietnam/1/2005(H5N1)) polymerase PB1
linear mRNA
GI:86753735


mRNA, complete cds




300. Influenza A virus
2,233 bp
DQ366305.1


(A/duck/Vietnam/1/2005(H5N1)) PA protein
linear mRNA
GI:86753745


mRNA, complete cds




301. Influenza A virus
1,779 bp
DQ366306.1


(A/duck/Vietnam/1/2005(H5N1)) hemagglutinin
linear mRNA
GI:86753755


mRNA, complete cds




302. Influenza A virus
1,565 bp
DQ366307.1


(A/duck/Vietnam/1/2005(H5N1)) nucleocapsid
linear mRNA
GI:86753765


mRNA, complete cds




303. Influenza A virus
1,401 bp
DQ366308.1


(A/duck/Vietnam/1/2005(H5N1)) neuraminidase
linear mRNA
GI:86753775


mRNA, complete cds




304. Influenza A virus
1,027 bp
DQ366309.1


(A/duck/Vietnam/1/2005(H5N1)) matrix protein
linear mRNA
GI:86753785


mRNA, complete cds




305. Influenza A virus
890 bp
DQ366326.1


(A/duck/Vietnam/8/05(H5N1)) nonstructural
linear mRNA
GI:86753719


protein 1 mRNA, complete cds




306. Influenza A virus
2,341 bp
DQ366319.1


(A/duck/Vietnam/8/05(H5N1)) polymerase PB2
linear mRNA
GI:86753729


mRNA, complete cds




307. Influenza A virus
2,341 bp
DQ366320.1


(A/duck/Vietnam/8/05(H5N1)) polymerase PB1
linear mRNA
GI:86753739


mRNA, complete cds




308. Influenza A virus
2,233 bp
DQ366321.1


(A/duck/Vietnam/8/05(H5N1)) PA protein mRNA,
linear mRNA
GI:86753749


complete cds




309. Influenza A virus
1,779 bp
DQ366322.1


(A/duck/Vietnam/8/05(H5N1)) hemagglutinin
linear mRNA
GI:86753759


mRNA, complete cds




310. Influenza A virus
1,565 bp
DQ366323.1


(A/duck/Vietnam/8/05(H5N1)) nucleocapsid
linear mRNA
GI:86753769


mRNA, complete cds




311. Influenza A virus
1,401 bp
DQ366324.1


(A/duck/Vietnam/8/05(H5N1)) neuraminidase
linear mRNA
GI:86753779


mRNA, complete cds




312. Influenza A virus
1,027 bp
DQ366325.1


(A/duck/Vietnam/8/05(H5N1)) matrix protein
linear mRNA
GI:86753789


mRNA, complete cds




313. Influenza A virus
876 bp
DQ354060.1


(A/duck/Yangzhou/232/2004(H5N1))
linear mRNA
GI:87128645


nonfunctional nonstructural protein (NS)




mRNA, complete sequence




314. Influenza A virus
2,281 bp
AY585523.1


(A/duck/Zhejiang/11/2000(H5N1)) polymerase
linear mRNA
GI:47156264


basic protein 2 (PB2) mRNA, complete cds




315. Influenza A virus
760 bp
AY585396.1


(A/duck/Zhejiang/11/2000(H5N1)) matrix
linear mRNA
GI:47156346


protein mRNA, complete cds




316. Influenza A virus
1,352 bp
AY585418.1


(A/duck/Zhejiang/11/2000(H5N1))
linear mRNA
GI:47156390


neuraminidase (NA) mRNA, complete cds




317. Influenza A virus
1,498 bp
AY585439.1


(A/duck/Zhejiang/11/2000(H5N1))
linear mRNA
GI:47156432


nucleoprotein (NP) mRNA, complete cds




318. Influenza A virus
687 bp
AY585460.1


(A/duck/Zhejiang/11/2000(H5N1))
linear mRNA
GI:47156474


nonstructural protein 1 (NS1) mRNA, partial cds




319. Influenza A virus
2,281 bp
AY585524.1


(A/duck/Zhejiang/52/2000(H5N1)) polymerase
linear mRNA
GI:47156266


basic protein 2 (PB2) mRNA, complete cds




320. Influenza A virus
760 bp
AY585397.1


(A/duck/Zhejiang/52/2000(H5N1)) matrix
linear mRNA
GI:47156348


protein mRNA, complete cds




321. Influenza A virus
1,423 bp
AY585419.1


(A/duck/Zhejiang/52/2000(H5N1))
linear mRNA
GI:47156392


neuraminidase (NA) mRNA, complete cds




322. Influenza A virus
1,499 bp
AY585440.1


(A/duck/Zhejiang/52/2000(H5N1))
linear mRNA
GI:47156434


nucleoprotein (NP) mRNA, complete cds




323. Influenza A virus
686 bp
AY585461.1


(A/duck/Zhejiang/52/2000(H5N1))
linear mRNA
GI:47156476


nonstructural protein 1 (NS1) mRNA, complete cds




324. Influenza A virus (A/Egypt/0636-
1,749 bp
EF382359.1


NAMRU3/2007(H5N1)) hemagglutinin (HA) mRNA,
linear mRNA
GI:124244205


complete cds




325. Influenza A virus
1,707 bp
EF110518.1


(A/goosander/Switzerland/V82/06 (H5N1))
linear mRNA
GI:119394674


hemagglutinin (HA) gene, complete cds




326. Influenza A virus
1,707 bp
AF148678.1


(A/goose/Guangdong/1/96/(H5N1))
linear mRNA
GI:5007022


hemagglutinin mRNA, complete cds




327. Influenza A virus
1,779 bp
DQ201829.1


(A/Goose/Huadong/1/2000(H5N1)) hemagglutinin
linear mRNA
GI:76786306


(HA) mRNA, complete cds




328. Influenza A virus
1,458 bp
DQ201830.1


(A/Goose/Huadong/1/2000(H5N1)) neuraminidase
linear mRNA
GI:76786308


(NA) mRNA, complete cds




329. Influenza A virus
2,287 bp
EF446768.1


(A/goose/Hungary/2823/2/2007(H5N1))
linear mRNA
GI:126428373


polymerase PB1 (PB1) mRNA, partial cds




330. Influenza A virus
2,274 bp
EF446769.1


(A/goose/Hungary/2823/2/2007(H5N1))
linear mRNA
GI:126428375


polymerase PB2 (PB2) mRNA, partial cds




331. Influenza A virus
2,175 bp
EF446770.1


(A/goose/Hungary/2823/2/2007(H5N1))
linear mRNA
GI:126428377


polymerase PA (PA) mRNA, complete cds




332. Influenza A virus
1,735 bp
EF446771.1


(A/goose/Hungary/2823/2/2007(H5N1))
linear mRNA
GI:126428379


hemagglutinin (HA) mRNA, complete cds




333. Influenza A virus
1,473 bp
EF446772.1


(A/goose/Hungary/2823/2/2007(H5N1))
linear mRNA
GI:126428381


nucleocapsid protein (NP) mRNA, partial cds




334. Influenza A virus
1,311 bp
EF446773.1


(A/goose/Hungary/2823/2/2007(H5N1))
linear mRNA
GI:126428383


neuraminidase (NA) mRNA, partial cds




335. Influenza A virus
971 bp
EF446774.1


(A/goose/Hungary/2823/2/2007(H5N1)) matrix
linear mRNA
GI:126428385


protein 1 (M1) mRNA, partial cds




336. Influenza A virus
795 bp
EF446775.1


(A/goose/Hungary/2823/2/2007(H5N1))
linear mRNA
GI:126428387


nonstructural protein 1 (NS1) mRNA, partial cds




337. Influenza A virus
2,277 bp
EF446776.1


(A/goose/Hungary/3413/2007(H5N1)) polymerase
linear mRNA
GI:126428389


PB1 (PB1) mRNA, partial cds




338. Influenza A virus
2,274 bp
EF446777.1


(A/goose/Hungary/3413/2007(H5N1)) polymerase
linear mRNA
GI:126428391


PB2 (PB2) mRNA, partial cds




339. Influenza A virus
2,163 bp
EF446778.1


(A/goose/Hungary/3413/2007 (H5N1)) polymerase
linear mRNA
GI:126428393


PA (PA) mRNA, partial cds




340. Influenza A virus
1,722 bp
EF446779.1


(A/goose/Hungary/3413/2007 (H5N1))
linear mRNA
GI:126428395


hemagglutinin (HA) mRNA, complete cds




341. Influenza A virus
1,463 bp
EF446780.1


(A/goose/Hungary/3413/2007 (H5N1))
linear mRNA
GI:126428397


nucleocapsid protein (NP) mRNA, partial cds




342. Influenza A virus
1,289 bp
EF446781.1


(A/goose/Hungary/3413/2007(H5N1))
linear mRNA
GI:126428399


neuraminidase (NA) mRNA, partial cds




343. Influenza A virus
955 bp
EF446782.1


(A/goose/Hungary/3413/2007(H5N1)) matrix
linear mRNA
GI:126428401


protein 1 (M1) mRNA, partial cds




344. Influenza A virus
805 bp
EF446783.1


(A/goose/Hungary/3413/2007(H5N1))
linear mRNA
GI:126428403


nonstructural protein 1 (NS1) mRNA, complete cds




345. Influenza A virus
877 bp
DQ354061.1


(A/goose/jiangsu/131/2002(H5N1))
linear mRNA
GI:87128646


nonfunctional nonstructural protein (NS)




mRNA, complete sequence




346. Influenza A virus
875 bp
DQ354062.1


(A/goose/Jiangsu/220/2003(H5N1))
linear mRNA
GI:87128647


nonstructural protein (NS) mRNA, complete cds




347. Influenza A virus
1,754 bp
DQ676840.1


(A/goose/Krasnoozerka/627/2005(H5N1))
linear mRNA
GI:108782531


hemagglutinin (HA) mRNA, complete cds




348. Influenza A virus
1,530 bp
DQ676841.1


(A/goose/Krasnoozerka/627/2005(H5N1))
linear mRNA
GI:108782533


nucleoprotein (NP) mRNA, complete cds




349. Influenza A virus
850 bp
DQ676842.1


(A/goose/Krasnoozerka/627/2005(H5N1))
linear mRNA
GI:108782535


nonstructural protein (NS) mRNA, complete cds




350. Influenza A virus
890 bp
DQ366318.1


(A/goose/Vietnam/3/05(H5N1)) nonstructural
linear mRNA
GI:86753717


protein 1 mRNA, complete cds




351. Influenza A virus
2,341 bp
DQ366311.1


(A/goose/Vietnam/3/05(H5N1)) polymerase PB2
linear mRNA
GI:86753727


mRNA, complete cds




352. Influenza A virus
2,341 bp
DQ366312.1


(A/goose/Vietnam/3/05(H5N1)) polymerase PB1
linear mRNA
GI:86753737


mRNA, complete cds




353. Influenza A virus
2,233 bp
DQ366313.1


(A/goose/Vietnam/3/05(H5N1)) PA protein
linear mRNA
GI:86753747


mRNA, complete cds




354. Influenza A virus
1,779 bp
DQ366314.1


(A/goose/Vietnam/3/05(H5N1)) hemagglutinin
linear mRNA
GI:86753757


mRNA, complete cds




355. Influenza A virus
1,565 bp
DQ366315.1


(A/goose/Vietnam/3/05(H5N1)) nucleocapsid
linear mRNA
GI:86753767


mRNA, complete cds




356. Influenza A virus
1,401 bp
DQ366316.1


(A/goose/Vietnam/3/05(H5N1)) neuraminidase
linear mRNA
GI:86753777


mRNA, complete cds




357. Influenza A virus
1,027 bp
DQ366317.1


(A/goose/Vietnam/3/05(H5N1)) matrix protein
linear mRNA
GI:86753787


mRNA, complete cds




358. Influenza A virus
1,700 bp
AF082043.1


(A/gull/Pennsylvania/4175/83(H5N1))
linear mRNA
GI:4240453


hemagglutinin H5 mRNA, partial cds




360. Influenza A virus
1,388 bp
AF028708.1


(A/HongKong/156/97(H5N1)) neuraminidase
linear mRNA
GI:2865377


mRNA, complete cds




361. Influenza A virus
1,741 bp
AF028709.1


(A/HongKong/156/97(H5N1)) hemagglutinin
linear mRNA
GI:2865379


mRNA, complete cds




362. Influenza A virus
1,549 bp
AF028710.1


(A/HongKong/156/97(H5N1)) nucleoprotein
linear mRNA
GI:2865381


mRNA, complete cds




363. Influenza A virus (A/hooded
1,451 bp
AM503028.1


vulture/Burkina Faso/1/2006(H5N1)) partial
linear mRNA
GI:147846292


mRNA for nucleoprotein (np gene)




364. Influenza A virus (A/hooded
827 bp
AM503038.1


vulture/Burkina Faso/1/2006(H5N1)) mRNA for
linear mRNA
GI:147846312


non-structural protein (ns gene)




365. Influenza A virus (A/hooded
2,169 bp
AM503047.1


vulture/Burkina Faso/1/2006(H5N1)) partial
linear mRNA
GI:147846330


mRNA for polymerase (pa gene)




366. Influenza A virus (A/hooded
1,686 bp
AM503065.1


vulture/Burkina Faso/1/2006(H5N1)) partial
linear mRNA
GI:147846855


mRNA for polymerase basic protein 1 (pb1 gene)




367. Influenza A virus (A/hooded
977 bp
AM503006.1


vulture/Burkina Faso/2/2006(H5N1)) partial
linear mRNA
GI:147846248


mRNA for matrix protein 1 (m1 gene)




368. Influenza A virus (A/hooded
1,336 bp
AM503017.1


vulture/Burkina Faso/2/2006(H5N1)) partial
linear mRNA
GI:147846270


mRNA for neuraminidase (na gene)




369. Influenza A virus (A/hooded
1,499 bp
AM503027.1


vulture/Burkina Faso/2/2006(H5N1)) partial
linear mRNA
GI:147846290


mRNA for nucleoprotein (np gene)




370. Influenza A virus (A/hooded
827 bp
AM503039.1


vulture/Burkina Faso/2/2006(H5N1)) mRNA for
linear mRNA
GI:147846314


non-structural protein (ns gene)




371. Influenza A virus (A/hooded
2,169 bp
AM503048.1


vulture/Burkina Faso/2/2006(H5N1)) partial
linear mRNA
GI:147846332


mRNA for polymerase (pa gene)




372. Influenza A virus (A/hooded
2,259 bp
AM503062.1


vulture/Burkina Faso/2/2006(H5N1)) partial
linear mRNA
GI:147846849


mRNA for polymerase basic protein 1 (pb1 gene)




373. Influenza A virus (A/hooded
2,315 bp
AM503066.1


vulture/Burkina Faso/2/2006(H5N1)) partial
linear mRNA
GI:147846857


mRNA for polymerase basic protein 2 (pb2 gene)




374. Influenza A virus
294 bp
EU014135.1


(A/Indonesia/CDC177/2005(H5N1)) M2 protein
linear mRNA
GI:151336850


mRNA, complete cds




375. Influenza A virus
294 bp
EU014138.1


(A/Indonesia/CDC298/2005(H5N1)) M2 protein
linear mRNA
GI:151336856


mRNA, complete cds




376. Influenza A virus
294 bp
EU014136.1


(A/Indonesia/CDC485/2006(H5N1)) M2 protein
linear mRNA
GI:151336852


mRNA, complete cds




377. Influenza A virus
294 bp
EU014134.1


(A/Indonesia/CDC530/2006(H5N1)) M2 protein
linear mRNA
GI:151336848


mRNA, complete cds




378. Influenza A virus
294 bp
EU014133.1


(A/Indonesia/CDC535/2006(H5N1)) M2 protein
linear mRNA
GI:151336846


mRNA, complete cds




379. Influenza A virus
294 bp
EU014132.1


(A/Indonesia/CDC540/2006(H5N1)) M2 protein
linear mRNA
GI:151336844


mRNA, complete cds




380. Influenza A virus
294 bp
EU014137.1


(A/Indonesia/CDC561/2006(H5N1)) M2 protein
linear mRNA
GI:151336854


mRNA, complete cds




381. Influenza A virus
294 bp
EU014139.1


(A/Indonesia/CDC60/2005(H5N1)) M2 protein
linear mRNA
GI:151336858


mRNA, complete cds




382. Influenza A virus
996 bp
U79453.1


(A/mallard/Wisconsin/428/75(H5N1))
linear mRNA
GI:1840071


hemagglutinin mRNA, partial cds




383. Influenza A virus
441 bp
JN157759.1


(A/ostrich/VRLCU/Egypt/2011(H5N1)) segment 4
linear mRNA
GI:338223304


hemagglutinin (HA) mRNA, partial cds




384. Influenza A virus
875 bp
DQ354063.1


(A/quail/yunnan/092/2002(H5N1))
linear mRNA
GI:87128649


nonstructural protein (NS) mRNA, complete cds




385. Influenza A virus
1,472 bp
AB241613.1


(A/R(Turkey/Ontario/7732/66-
linear mRNA
GI:82581222


Bellamy/42)(H5N1)) HA mRNA for




hemagglutinin, partial cds




386. Influenza A virus (A/Thailand/LFPN-
1,350 bp
AY679513.1


2004/2004(H5N1)) neuraminidase mRNA,
linear mRNA
GI:50843945


complete cds




387. Influenza A virus (A/Thailand/LFPN-
1,704 bp
AY679514.1


2004/2004(H5N1)) hemagglutinin mRNA,
linear mRNA
GI:50843949


complete cds




388. Influenza A virus (A/tiger/Thailand/CU-
534 bp
DQ017251.1


T4/04(H5N1)) polymerase basic protein 2
linear mRNA
GI:65329524


(PB2) mRNA, partial cds




389. Influenza A virus (A/tiger/Thailand/CU-
582 bp
DQ017252.1


T5/04(H5N1)) polymerase basic protein 2
linear mRNA
GI:65329536


(PB2) mRNA, partial cds




390. Influenza A virus (A/tiger/Thailand/CU-
564 bp
DQ017253.1


T6/04(H5N1)) polymerase basic protein 2
linear mRNA
GI:65329553


(PB2) mRNA, partial cds




391. Influenza A virus (A/tiger/Thailand/CU-
582 bp
DQ017254.1


T8/04(H5N1)) polymerase basic protein 2
linear mRNA
GI:65329568


(PB2) mRNA, partial cds




392. Influenza A virus
1,695 bp
EF441263.1


(A/turkey/England/250/2007(H5N1))
linear mRNA
GI:129307104


hemagglutinin (HA) mRNA, partial cds




393. Influenza A virus
943 bp
EF441264.1


(A/turkey/England/250/2007(H5N1)) matrix
linear mRNA
GI:129307106


protein (M) mRNA, partial cds




394. Influenza A virus
812 bp
EF441265.1


(A/turkey/England/250/2007(H5N1))
linear mRNA
GI:129307109


nonstructural protein 1 (NS1) mRNA, complete cds




395. Influenza A virus
2,185 bp
EF441266.1


(A/turkey/England/250/2007(H5N1)) polymerase
linear mRNA
GI:129307111


PA (PA) mRNA, complete cds




396. Influenza A virus
2,272 bp
EF441267.1


(A/turkey/England/250/2007(H5N1)) polymerase
linear mRNA
GI:129307113


PB2 (PB2) mRNA, partial cds




397. Influenza A virus
1,396 bp
EF441268.1


(A/turkey/England/250/2007(H5N1))
linear mRNA
GI:129307115


nucleocapsid (NP) mRNA, partial cds




398. Influenza A virus
2,288 bp
EF441269.1


(A/turkey/England/250/2007(H5N1)) polymerase
linear mRNA
GI:129307117


PB1 (PB1) mRNA, partial cds




399. Influenza A virus
1,276 bp
EF441270.1


(A/turkey/England/250/2007(H5N1))
linear mRNA
GI:129307119


neuraminidase (NA) mRNA, partial cds




A/chicken/Burkina Faso/13.1/2006(H5N1)

AM503016.1


neuraminidase (NA)




A/chicken/Crimea/04/2005(H5N1) neuraminidase

DQ650661.1


(NA)




A/chicken/Crimea/04/2005(H5N1) hemagglutinin

DQ650659.1


A/chicken/Crimea/08/2005(H5N1) polymerase

DQ650669.1


basic protein 1 (PB1)




A/chicken/Crimea/08/2005(H5N1) neuraminidase

DQ650665.1


(NA)




A/chicken/Crimea/08/2005(H5N1) hemagglutinin

DQ650663.1


(HA)




A/chicken/Guangxi/12/2004(H5N1)

DQ366334.1


nonstructural protein 1




A/chicken/Guangxi/12/2004(H5N1)

DQ366332.1


neuraminidase




A/chicken/Guangxi/12/2004(H5N1)

DQ366330.1


hemagglutinin




A/duck/Kurgan/08/2005(H5N1) nucleoprotein

DQ449643.1


(NP)
















TABLE 10







Other Influenza A Antigens (H1N*, H2N*, H3N*)











GenBank/GI


Strain/Protein
Length
Accession Nos.





H1N*




Influenza A virus (A/duck/Hong
1,402 bp
U49097.1


Kong/193/1977(H1N2)) nucleoprotein (NP)
linear mRNA
GI:1912392


mRNA, partial cds




Influenza A virus (A/duck/Hong
258 bp
U48285.1


Kong/193/1977(H1N2)) polymerase (PB1) mRNA,
linear mRNA
GI:1912374


partial cds




Influenza A virus (A/England/2/2002(H1N2))
795 bp
AJ519455.1


partial NS1 gene for non structural protein
linear mRNA
GI:31096426


1 and partial NS2 gene for non structural




protein 2, genomic RNA




Influenza A virus (A/England/3/02(H1N2))
384 bp
AJ489497.1


partial mRNA for nucleoprotein (np gene)
linear mRNA
GI:27526856


Influenza A virus (A/England/3/02(H1N2))
442 bp
AJ489488.1


partial mRNA for polymerase subunit 2 (pb2
linear mRNA
GI:27526838


gene)




Influenza A virus (A/England/5/02(H1N2))
384 bp
AJ489498.1


partial mRNA for nucleoprotein (np gene)
linear mRNA
GI:27526858


Influenza A virus (A/England/5/02(H1N2))
442 bp
AJ489489.1


partial mRNA for polymerase subunit 2 (pb2
linear mRNA
GI:27526840


gene)




Influenza A virus (A/England/57/02(H1N2))
384 bp
AJ489499.1


partial mRNA for nucleoprotein (np gene)
linear mRNA
GI:27526860


Influenza A virus (A/England/57/02(H1N2))
442 bp
AJ489492.1


partial mRNA for polymerase subunit 2 (pb2
linear mRNA
GI:27526846


gene)




Influenza A virus (A/England/691/01(H1N2))
384 bp
AJ489496.1


partial mRNA for nucleoprotein (np gene)
linear mRNA
GI:27526854


Influenza A virus (A/England/73/02(H1N2))
384 bp
AJ489500.1


partial mRNA for nucleoprotein (np gene)
linear mRNA
GI:27526862


Influenza A virus (A/England/73/02(H1N2))
442 bp
AJ489493.1


partial mRNA for polymerase subunit 2 (pb2
linear mRNA
GI:27526848


gene)




Influenza A virus (A/England/90/02(H1N2))
384 bp
AJ489501.1


partial mRNA for nucleoprotein (np gene)
linear mRNA
GI:27526864


Influenza A virus (A/England/90/02(H1N2))
442 bp
AJ489490.1


partial mRNA for polymerase subunit 2 (pb2
linear mRNA
GI:27526842


gene)




Influenza A virus (A/England/97/02(H1N2))
384 bp
AJ489502.1


partial mRNA for nucleoprotein (np gene)
linear mRNA
GI:27526866


Influenza A virus (A/England/97/02(H1N2))
442 bp
AJ489491.1


partial mRNA for polymerase subunit 2 (pb2
linear mRNA
GI:27526844


gene)




Influenza A virus (A/England/627/01(H1N2))
384 bp
AJ489494.1


partial mRNA for nucleoprotein (np gene)
linear mRNA
GI:27526850


Influenza A virus (A/England/627/01(H1N2))
442 bp
AJ489485.1


partial mRNA for polymerase subunit 2 (pb2
linear mRNA
GI:27526832


gene)




Influenza A virus (A/England/691/01(H1N2))
442 bp
AJ489487.1


partial mRNA for polymerase subunit 2 (pb2
linear mRNA
GI:27526836


gene)




Influenza A virus (A/Egypt/96/2002(H1N2))
747 bp
AJ519457.1


partial NS1 gene for non structural protein
linear mRNA
GI:31096432


1 and partial NS2 gene for non structural




protein 2, genomic RNA




Influenza A virus (A/Israel/6/2002(H1N2))
773 bp
AJ519456.1


partial NS1 gene for non structural protein
linear mRNA
GI:31096429


1 and partial NS2 gene for non structural




protein 2, genomic RNA




Influenza A virus (A/Saudi
772 bp
AJ519453.1


Arabia/2231/2001(H1N2)) partial NS1 gene for
linear mRNA
GI:31096420


non structural protein 1 and partial NS2




gene for non structural protein 2, genomic RNA




Influenza A virus (A/Scotland/122/01(H1N2))
384 bp
AJ489495.1


partial mRNA for nucleoprotein (np gene)
linear mRNA
GI:27526852


Influenza A virus (A/Scotland/122/01(H1N2))
442 bp
AJ489486.1


partial mRNA for polymerase subunit 2 (pb2
linear mRNA
GI:27526834


gene)




Influenza A virus
832 bp
AY861443.1


(A/swine/Bakum/1832/2000(H1N2))
linear mRNA
GI:57791765


hemagglutinin (HA) mRNA, partial cds




Influenza A virus
467 bp
AY870645.1


(A/swine/Bakum/1832/2000(H1N2))
linear mRNA
GI:58042754


neuraminidase mRNA, partial cds




Influenza A virus (A/swine/Cotes
1,039 bp
AM503547.1


d'Armor/0040/2007(H1N2)) segment 4 partial
linear mRNA
GI:225578611


mRNA




Influenza A virus (A/swine/Cotes
1,136 bp
AM490224.3


d'Armor/0136_17/2006(H1N2)) partial mRNA for
linear mRNA
GI:222062921


haemagglutinin precursor (HA1 gene)




Influenza A virus
1,778 bp
AF085417.1


(A/swine/England/72685/96(H1N2))
linear mRNA
GI:3831770


haemagglutinin precursor, mRNA, complete cds




Influenza A virus
1,778 bp
AF085416.1


(A/swine/England/17394/96(H1N2))
linear mRNA
GI:3831768


haemagglutinin precursor, mRNA, complete cds




Influenza A virus
1,778 bp
AF085415.1


(A/swine/England/690421/95(H1N2))
linear mRNA
GI:3831766


haemagglutinin precursor, mRNA, complete cds




Influenza A virus
1,778 bp
AF085414.1


(A/swine/England/438207/94(H1N2))
linear mRNA
GI:3831764


haemagglutinin precursor, mRNA, complete cds




Influenza A virus
1,427 bp
AY129157.1


(A/Swine/Korea/CY02/02(H1N2)) neuraminidase
linear mRNA
GI:24286064


(NA) mRNA, complete cds




Influenza A virus
952 bp
AY129158.1


(A/Swine/Korea/CY02/02(H1N2)) matrix protein
linear mRNA
GI:24286066


(M) mRNA, complete cds




Influenza A virus
1,542 bp
AY129159.1


(A/Swine/Korea/CY02/02(H1N2)) nucleoprotein
linear mRNA
GI:24286069


(NP) mRNA, complete cds




Influenza A virus
842 bp
AY129160.1


(A/Swine/Korea/CY02/02(H1N2)) nonstructural
linear mRNA
GI:24286081


protein (NS) mRNA, complete cds




Influenza A virus
2,165 bp
AY129161.1


(A/Swine/Korea/CY02/02(H1N2)) polymerase
linear mRNA
GI:24286087


acidic protein 2 (PA) mRNA, complete cds




Influenza A virus
2,274 bp
AY129162.1


(A/Swine/Korea/CY02/02(H1N2)) polymerase
linear mRNA
GI:24286096


subunit 1 (PB1) mRNA, complete cds




Influenza A virus
2,334 bp
AY129163.1


(A/Swine/Korea/CY02/02(H1N2)) polymerase
linear mRNA
GI:24286100


subunit 2 (PB2) mRNA, complete cds




Influenza A virus
1,778 bp
AF085413.1


(A/swine/Scotland/410440/94(H1N2))
linear mRNA
GI:3831762


haemagglutinin precursor, mRNA, complete cds




Influenza A virus (A/swine/Spain/80598-
291 bp
EU305436.1


LP4/2007(H1N2)) matrix protein 2 (M2) mRNA,
linear mRNA
GI:168830657


partial cds




Influenza A virus
975 bp
AJ517813.1


(A/Switzerland/3100/2002(H1N2)) partial HA
linear mRNA
GI:38422519


gene for Haemagglutinin, genomic RNA




Influenza A virus (A/duck/Hong
1,387 bp
U49095.1


Kong/717/1979(H1N3)) nucleoprotein (NP)
linear mRNA
GI:1912388


mRNA, partial cds




Influenza A virus (A/duck/Hong
265 bp
U48281.1


Kong/717/1979(H1N3)) polymerase (PB1) mRNA,
linear mRNA
GI:1912366


partial cds




Influenza A virus (A/herring gull/New
971 bp
AY664422.1


Jersey/780/86 (H1N3)) nonfunctional matrix
linear mRNA
GI:51011826


protein mRNA, partial sequence




Influenza A virus
997 bp
AY664426.1


(A/mallard/Alberta/42/77(H1N6))
linear mRNA
GI:51011830


nonfunctional matrix protein mRNA, partial




sequence




Influenza A virus
1,020 bp
U85985.1


(A/swine/England/191973/92(H1N7)) matrix
linear mRNA
GI:1835733


protein M1 mRNA, complete cds




Influenza A virus
1,524 bp
U85987.1


(A/swine/England/191973/92(H1N7))
linear mRNA
GI:1835737


nucleoprotein mRNA, complete cds




Influenza A virus
1,458 bp
U85988.1


(A/swine/England/191973/92(H1N7))
linear mRNA
GI:1835739


neuraminidase mRNA, complete cds




Influenza A virus
1,698 bp
U85986.1


(A/swine/England/191973/92 (H1N7) )
linear mRNA
GI:1835735


haemagglutinin HA mRNA, partial cds




H2N*




Influenza A virus (A/ruddy
917 bp
AY664465.1


turnstone/Delaware/81/93 (H2N1))
linear mRNA
GI:51011869


nonfunctional matrix protein mRNA, partial




sequence




Influenza A virus (A/ruddy
968 bp
AY664429.1


turnstone/Delaware/34/93 (H2N1))
linear mRNA
GI:51011833


nonfunctional matrix protein mRNA, partial




sequence




Influenza A virus
925 bp
AY664466.1


(A/Shorebird/Delaware/122/97(H2N1))
linear mRNA
GI:51011870


nonfunctional matrix protein mRNA, partial




sequence




Influenza A virus
958 bp
AY664454.1


(A/shorebird/Delaware/138/97 (H2N1))
linear mRNA
GI:51011858


nonfunctional matrix protein mRNA, partial




sequence




Influenza A virus
958 bp
AY664457.1


(A/shorebird/Delaware/111/97 (H2N1))
linear mRNA
GI:51011861


nonfunctional matrix protein mRNA, partial




sequence




Influenza A virus
979 bp
AY664442.1


(A/shorebird/Delaware/24/98 (H2N1))
linear mRNA
GI:51011846


nonfunctional matrix protein mRNA, partial




sequence




Influenza virus type A/Leningrad/134/17/57
2,233 bp
M81579.1


(H2N2) PA RNA, complete cds
linear mRNA
GI:324935


Influenza A virus (STRAIN A/MALLARD/NEW
2,151 bp
AJ243994.1


YORK/6750/78) partial mRNA for PA protein
linear mRNA
GI:5918195


Influenza A virus (A/X-7(F1)/(H2N2))
1,467 bp
M11205.1


neuraminidase mRNA, complete cds
linear mRNA
GI:323969


Influenza A virus (A/mallard/Alberta/77/77
1,009 bp
AY664425.1


(H2N3)) nonfunctional matrix protein mRNA,
linear mRNA
GI:51011829


partial sequence




Influenza A virus
968 bp
AY664447.1


(A/mallard/Alberta/226/98(H2N3))
linear mRNA
GI:51011851


nonfunctional matrix protein mRNA, partial




sequence




Influenza A virus (A/sanderling/New
846 bp
AY664477.1


Jersey/766/86 (H2N7)) nonfunctional matrix
linear mRNA
GI:51011881


protein mRNA, partial sequence




Influenza A virus (A/laughing gull/New
907 bp
AY664471.1


Jersey/798/86 (H2N7)) nonfunctional matrix
linear mRNA
GI:51011875


protein mRNA, partial sequence




Influenza A virus (A/herring
960 bp
AY664440.1


gull/Delaware/471/1986(H2N7)) nonfunctional
linear mRNA
GI:51011844


matrix protein mRNA, partial sequence




Influenza A virus (A/ruddy
1,011 bp
AY664423.1


turnstone/Delaware/142/98 (H2N8))
linear mRNA
GI:51011827


nonfunctional matrix protein mRNA, partial




sequence




Influenza A virus (A/pintail/Alberta/293/77
906 bp
AY664473.1


(H2N9)) nonfunctional matrix protein mRNA,
linear mRNA
GI:51011877


partial sequence




Influenza A virus (A/blue-winged
961 bp
AY664449.1


teal/Alberta/16/97 (H2N9)) nonfunctional
linear mRNA
GI:51011853


matrix protein mRNA, partial sequence




Influenza A virus (A/Laughing gull/New
952 bp
AY664437.1


Jersey/75/85 (H2N9)) nonfunctional matrix
linear mRNA
GI:51011841


protein mRNA, partial sequence




Influenza A virus (A/mallard/Alberta/205/98
959 bp
AY664450.1


(H2N9)) nonfunctional matrix protein mRNA,
linear mRNA
GI:51011854


partial sequence




H3N*




Influenza A virus (A/duck/Eastern
1,458 bp
EU429755.1


China/267/2003(H3N1)) segment 6
linear mRNA
GI:167859475


neuraminidase (NA) mRNA, complete cds




Influenza A virus (A/duck/Eastern
1,458 bp
EU429754.1


China/253/2003(H3N1)) segment 6
linear mRNA
GI:167859473


neuraminidase (NA) mRNA, complete cds




Influenza A virus (A/duck/Eastern
1,458 bp
EU429753.1


China/252/2003(H3N1)) segment 6
linear mRNA
GI:167859471


neuraminidase (NA) mRNA, complete cds




Influenza A virus (A/duck/Eastern
1,458 bp
EU429752.1


China/243/2003(H3N1)) segment 6
linear mRNA
GI:167859469


neuraminidase (NA) mRNA, complete cds




Influenza A virus (A/duck/Eastern
1,458 bp
EU429734.1


China/262/2003(H3N1)) segment 6
linear mRNA
GI:167859433


neuraminidase (NA) mRNA, complete cds




Influenza A virus (A/duck/Eastern
1,459 bp
EU429733.1


China/233/2003(H3N1)) segment 6
linear mRNA
GI:167859431


neuraminidase (NA) mRNA, complete cds




Influenza A virus (A/duck/Eastern
1,458 bp
EU429723.1


China/213/2003(H3N1)) segment 6
linear mRNA
GI:167859411


neuraminidase (NA) mRNA, complete cds




Influenza A virus (A/duck/Eastern
1,458 bp
EU429719.1


China/341/2003(H3N1)) segment 6
linear mRNA
GI:167859403


neuraminidase (NA) mRNA, complete cds




Influenza A virus (A/duck/Eastern
1,458 bp
EU429718.1


China/01/2002(H3N1)) segment 6 neuraminidase
linear mRNA
GI:167859401


(NA) mRNA, complete cds




Influenza A virus (A/mallard/Alberta/22/76
1,013 bp
AY664434.1


(H3N6)) nonfunctional matrix protein mRNA,
linear mRNA
GI:51011838


partial sequence




Influenza A virus
970 bp
AY664443.1


(A/mallard/Alberta/199/99(H3N6))
linear mRNA
GI:51011847


nonfunctional matrix protein mRNA, partial




sequence




Influenza A virus
922 bp
AY664461.1


(A/shorebird/Delaware/222/97 (H3N6))
linear mRNA
GI:51011865


nonfunctional matrix protein mRNA, partial




sequence




Influenza A virus (A/Duck/Hokkaido/8/80
984 bp
AF079570.1


(H3N8)) hemagglutinin precursor, mRNA,
linear mRNA
GI:3414978


partial cds




Influenza A virus (A/Duck/Hokkaido/8/80
1,497 bp
AF079571.1


(H3N8)) nucleoprotein mRNA, complete cds
linear mRNA
GI:3414980


Influenza A virus
1,461 bp
EU429797.1


(A/duck/Ukraine/1/1963(H3N8)) segment 6
linear mRNA
GI:167859559


neuraminidase (NA) mRNA, complete cds




Influenza A virus (A/duck/Eastern
1,460 bp
EU429698.1


China/19/2004(H3N8)) segment 6 neuraminidase
linear mRNA
GI:167859361


(NA) mRNA, complete cds




Influenza A virus (A/duck/Eastern
1,460 bp
EU429700.1


China/90/2004(H3N8)) segment 6 neuraminidase
linear mRNA
GI:167859365


(NA) mRNA, complete cds




Influenza A virus (A/duck/Eastern
1,460 bp
EU429787.1


China/18/2005(H3N8)) segment 6 neuraminidase
linear mRNA
GI:167859539


(NA) mRNA, complete cds




Influenza A virus (A/duck/Eastern
1,460 bp
EU429788.1


China/119/2005(H3N8)) segment 6
linear mRNA
GI:167859541


neuraminidase (NA) mRNA, complete cds




Influenza A virus
1,061 bp
AF197246.1


(A/equine/Argentina/1/96(H3N8))
linear mRNA
GI:6651512


hemagglutinin precursor (HA1) mRNA, partial




cds




Influenza A virus
1,061 bp
AF197245.1


(A/equine/Argentina/2/94(H3N8))
linear mRNA
GI:6651510


hemagglutinin precursor (HA1) mRNA, partial




cds




Influenza A virus
1,061 bp
AF197244.1


(A/equine/Argentina/1/95(H3N8))
linear mRNA
GI:6651508


hemagglutinin precursor (HA1) mRNA, partial




cds




Influenza A virus HA partial gene for
1,026 bp
AJ223194.1


haemagglutinin, genomic RNA, strain
linear mRNA
GI:2780201


A/equine/Berlin/3/89(H3N8)




Influenza A virus HA partial gene for
1,006 bp
AJ223195.1


haemagglutinin, genomic RNA, strain
linear mRNA
GI:2780203


A/equine/Berlin/4/89(H3N8)




Influenza A virus
1,061 bp
AF197242.1


(A/equine/Florida/1/94(H3N8)) hemagglutinin
linear mRNA
GI:6651504


precursor (HA1) mRNA, partial cds




Influenza A virus
695 bp
AY328471.1


(A/equine/Grobois/1/98(H3N8)) nonstructural
linear mRNA
GI:32966577


protein NS1 mRNA, complete cds




Influenza A virus (A/equi
473 bp
AY919314.1


2/Gotland/01(H3N8)) hemagglutinin HA1
linear mRNA
GI:60250543


subunit mRNA, partial cds




Influenza A virus (A/eq/Kentucky/81(H3N8))
1,763 bp
U58195.1


hemagglutinin mRNA, complete cds
linear mRNA
GI:1377873


Influenza A virus
1,061 bp
AF197247.1


(A/equine/Kentucky/9/95(H3N8)) hemagglutinin
linear mRNA
GI:6651514


precursor (HA1) mRNA, partial cds




Influenza A virus
1,061 bp
AF197248.1


(A/equine/Kentucky/1/96(H3N8)) hemagglutinin
linear mRNA
GI:6651516


precursor (HA1) mRNA, partial cds




Influenza A virus
1,061 bp
AF197249.1


(A/equine/Kentucky/1/97(H3N8)) hemagglutinin
linear mRNA
GI:6651518


precursor (HA1) mRNA, partial cds




Influenza A virus
1,061 bp
AF197241.1


(A/equine/Kentucky/1/98(H3N8)) hemagglutinin
linear mRNA
GI:6651502


precursor (HA1) mRNA, partial cds




Influenza A virus
1,497 bp
AY383753.1


(A/equine/Santiago/85(H3N8)) nucleoprotein
linear mRNA
GI:37223511


mRNA, complete cds




Influenza A virus
1,698 bp
AY383755.1


(A/equine/Santiago/85(H3N8)) hemagglutinin
linear mRNA
GI:37223515


mRNA, complete cds




Influenza A virus
1,413 bp
AY383754.1


(A/equine/Santiago/85(H3N8)) neuraminidase
linear mRNA
GI:37223513


mRNA, complete cds




Influenza A virus
1,061 bp
AF197243.1


(A/equine/Saskatoon/1/90(H3N8))
linear mRNA
GI:6651506


hemagglutinin precursor (HA1) mRNA, partial




cds




Influenza A virus (A/mallard/Alberta/114/97
1,010 bp
AY664432.1


(H3N8)) nonfunctional matrix protein mRNA,
linear mRNA
GI:51011836


partial sequence




Influenza A virus (A/mallard/Alberta/167/98
961 bp
AY664489.1


(H3N8)) nonfunctional matrix protein mRNA,
linear mRNA
GI:51011893


partial sequence




Influenza A virus
970 bp
AY664445.1


(A/pintail/Alberta/37/99(H3N8))
linear mRNA
GI:51011849


nonfunctional matrix protein mRNA, partial




sequence




Influenza A virus
922 bp
AY664455.1


(A/sanderling/Delaware/65/99 (H3N8))
linear mRNA
GI:51011859


nonfunctional matrix protein mRNA, partial




sequence
















TABLE 11







Other Influenza A Antigens (H4N*-H13N*)









GenBank


Strain/Protein
Access No.





A/chicken/Singapore/1992(H4N1) M2 protein
EU014144.1


A/mallard/Alberta/47/98(H4N1) nonfunctional matrix protein
AY664488.1


A/duck/Hong Kong/412/1978(H4N2) polymerase (PB1)
U48279.1


A/mallard/Alberta/300/77 (H4N3) nonfunctional matrix protein
AY664480.1


A/Duck/Czechoslovakia/56(H4N6) segment 4 hemagglutinin
AF290436.1


A/duck/Eastern China/376/2004(H4N6) segment 6neuraminidase (NA)
EU429792.1


A/duck/Eastern China/01/2007(H4N6) segment 6 neuraminidase (NA)
EU429790.1


A/duck/Eastern China/216/2007(H4N6) segment 6 neuraminidase
EU429789.1


(NA)



A/duck/Eastern China/166/2004(H4N6) segment 6 neuraminidase
EU429746.1


(NA)



A/duck/Eastern China/02/2003(H4N6) segment 6 neuraminidase (NA)
EU429713.1


A/duck/Eastern China/160/2002(H4N6) segment 6 neuraminidase
EU429706.1


(NA)



A/mallard/Alberta/111/99(H4N6) nonfunctional matrix protein
AY664482.1


A/mallard/Alberta/213/99 (H4N6) nonfunctional matrix protein
AY664460.1


A/mallard/Alberta/30/98 (H4N6) nonfunctional matrix protein
AY664484.1


A/blue-winged teal/Alberta/96/76 (H4N8) nonfunctional matrix
AY664420.1


protein



A/chicken/Florida/25717/1993(H5N2) hemagglutinin
U05332.1


A/chicken/Hidalgo/26654-1368/1994(H5N2) hemagglutinin (HA)
U37172.1


A/chicken/Jalisco/14585-660/1994(H5N2) hemagglutinin (HA)
U37181.1


A/chicken/Mexico/26654-1374/1994(H5N2) hemagglutinin (HA)
U37173.1


A/chicken/Mexico/31381-3/1994(H5N2) hemagglutinin (HA)
U37176.1


A/chicken/Mexico/31381-6/1994(H5N2) hemagglutinin (HA)
U37175.1


A/chicken/Mexico/31381-4/1994(H5N2) hemagglutinin (HA)
U37174.1


A/chicken/Mexico/31381-5/1994(H5N2) hemagglutinin (HA)
U37169.1


A/chicken/Mexico/31381-8/1994(H5N2) hemagglutinin (HA)
U37170.1


A/Chicken/Mexico/31381-Avilab/94(H5N2)hemagglutinin (HA)
L46585.1


A/chicken/Mexico/31382-1/1994(H5N2)hemagglutinin (HA)
U37168.1


A/chicken/Mexico/31381-2/1994(H5N2) hemagglutinin (HA)
U37167.1


A/chicken/Mexico/31381-1/1994(H5N2) hemagglutinin (HA)
U37166.1


A/chicken/Mexico/31381-7/1994(H5N2) hemagglutinin (HA)
U37165.1


A/chicken/Pennsylvania/13609/1993(H5N2) hemagglutinin
U05331.1


A/chicken/Pennsylvania/1/1983(H5N2) hemagglutinin esterase
M18001.1


precursor



A/chicken/Pennsylvania/1370/1983(H5N2) hemagglutinin esterase
M10243.1


precursor



A/Chicken/Puebla/8623-607/94(H5N2) hemagglutinin (HA)
L46586.1


A/chicken/Puebla/14586-654/1994(H5N2) hemagglutinin (HA)
U37180.1


A/chicken/Puebla/14585-622/1994(H5N2) hemagglutinin (HA)
U37179.1


A/chicken/Puebla/8623-607/1994(H5N2)hemagglutinin (HA)
U37178.1


A/chicken/Puebla/8624-604/1994(H5N2) hemagglutinin (HA)
U37177.1


A/Chicken/Queretaro/14588-19/95(H5N2) hemagglutinin (HA)
L46587.1


A/chicken/Queretaro/7653-20/95(H5N2) hemagglutinin (HA)
U79448.1


A/chicken/Queretaro/26654-1373/1994(H5N2) hemagglutinin (HA)
U37171.1


A/chicken/Queretaro/14588-19/1994(H5N2)hemagglutinin (HA)
U37182.1


A/chicken/Singapore/98(H5N2) matrix protein 2 (M2)
EF682127.1


A/chicken/Taiwan/1209/03(H5N2) hemagglutinin protein (HA)
AY573917.1


A/chicken/Taiwan/1209/03(H5N2) neuraminidase
AY573918.1


A/duck/Eastern China/64/2004(H5N2) segment 6 neuraminidase (NA)
EU429791.1


A/duck/Eastern China/264/2002(H5N2) segment 6 neuraminidase
EU429744.1


(NA)



A/duck/Eastern China/01/2001(H5N2) segment 6 neuraminidase (NA)
EU429728.1


A/duck/Eastern China/06/2000(H5N2) segment 6 neuraminidase
EU429722.1


(NA)



A/duck/Hong Kong/342/78(H5N2) matrix protein 1 (M) and matrix
DQ107452.1


protein 2 (M)



A/duck/Hong Kong/342/78(H5N2) hemagglutinin precursor
U20475.1


A/duck/Michigan/80(H5N2) hemagglutinin 1 chain
U20474.1


A/duck/Michigan/80(H5N2) hemagglutinin
U79449.1


A/duck/MN/1564/81(H5N2) matrix protein 1 (M) and matrix protein
DQ107467.1


2 (M)



A/duck/Mongolia/54/2001(H5N2) hemagglutinin (HA)
AB241614.2


A/duck/Primorie/2621/01(H5N2) hemagglutinin (HA)
AJ621811.3


A/duck/Primorie/2621/01(H5N2)nucleoprotein (NP )
AJ621812.1


A/duck/Primorie/2621/01(H5N2) nonstructural protein (NS)
AJ621813.1


A/duck/Pennsylvania/84(H5N2) hemagglutinin 1chain
U20473.1


A/duck/Potsdam/1402-6/86(H5N2) hemagglutinin H5
AF082042.1


A/emu/Texas/39442/93(H5N2) hemaglutinin
U28920.1


A/emu/Texas/39442/93(H5N2) hemaglutinin
U28919.1


A/mallard/Alberta/645/80(H5N2) matrix protein 1 (M) and matrix
DQ107471.1


protein 2 (M)



A/mallard/AR/1C/2001(H5N2) matrix protein 1 (M) and matrix
DQ107463.1


protein 2 (M)



A/mallard/NY/189/82(H5N2) matrix protein 1 (M) and matrix
DQ107465.1


protein 2 (M)



A/mallard/MN/25/80(H5N2) matrix protein 1 (M) and matrix
DQ107473.1


protein 2 (M)



A/mallard/MI/18/80(H5N2) matrix protein 1 (M) and matrix
DQ107470.1


protein 2 (M)



A/mallard/Ohio/345/88(H5N2) hemagglutinin
U79450.1


A/parrot/CA/6032/04(H5N2) polymerase basic protein 2 (PB2)
DQ256390.1


A/parrot/CA/6032/04(H5N2) polymerase basic protein 1 (PB1)
DQ256389.1


A/parrot/CA/6032/04(H5N2) matrix protein (M)
DQ256384.2


A/parrot/CA/6032/04(H5N2) hemagglutinin (HA)
DQ256383.1


A/parrot/CA/6032/04(H5N2) neuraminidase (NA)
DQ256385.1


A/parrot/CA/6032/04(H5N2) polymerase basic protein 2 (PB2)
DQ256390.1


A/parrot/CA/6032/04(H5N2) nucleoprotein (NP)
DQ256386.1


A/parrot/CA/6032/04(H5N2)) polymerase (PA)
DQ256388.1


A/ruddy turnstone/Delaware/244/91 (H5N2) nonfunctional matrix
AY664474.1


protein



A/ruddy turnstone/Delaware/244/91 (H5N2)
U05330.1


A/turkey/Colorado/72(H5N2) hemagglutinin 1 chain (HA)
U20472.1


A/turkey/England/N28/73 (H5N2) hemagglutinin
AY500365.1


A/turkey/TX/14082/81(H5N2) matrix protein 1 (M) and matrix
DQ107464.1


protein 2 (M)



A/turkey/MN/1704/82(H5N2)) matrix protein 1 (M) and matrix
DQ107472.1


protein 2 (M)



A/turkey/Minnesota/10734/95(H5N2)) hemagglutinin
U79455.1


A/turkey/Minnesota/3689-1551/81(H5N2) hemagglutinin
U79454.1


A/chicken/Singapore/1997(H5N3) M2 protein
EU014141.1


A/duck/Hokkaido/299/04(H5N3) hemagglutinin (HA)
AB241626.1


A/duck/Hokkaido/193/04(H5N3) hemagglutinin (HA)
AB241625.1


A/duck/Hokkaido/101/04(H5N3) hemagglutinin (HA)
AB241624.1


A/duck/Hokkaido/447/00(H5N3) hemagglutinin (HA)
AB241620.1


A/duck/Hokkaido/69/00(H5N3) hemagglutinin (HA)
AB241619.1


A/duck/Hong Kong/205/77(H5N3) hemagglutinin H5
AF082038.1


A/duck/Hong Kong/698/79(H5N3) hemagglutinin H5
AF082039.1


A/duck/Hong Kong/308/78(H5N3) matrix protein 1 (M) and matrix
DQ107457.1


protein 2 (M)



A/duck/Hong Kong/825/80(H5N3) matrix protein 1 (M) and matrix
DQ107455.1


protein 2 (M)



A/duck/Hong Kong/820/80(H5N3) matrix protein 1 (M) and matrix
DQ107453.1


protein 2 (M)



A/duck/Hong Kong/205/77(H5N3) matrix protein 1 (M) and matrix
DQ107456.1


protein 2 (M)



A/Duck/Ho Chi Minh/014/78(H5N3) segment 4 hemagglutinin
AF290443.1


A/duck/Jiangxi/6151/2003(H5N3) matrix protein 1 (M) and matrix
DQ107451.1


protein 2 (M)



A/duck/Malaysia/F119-3/97(H5N3) hemagglutinin
AF303057.1


A/duck/Miyagi/54/76(H5N3)hemagglutinin (HA)
AB241615.1


A/duck/Mongolia/596/01(H5N3) hemagglutinin HA)
AB241622.1


A/duck/Mongolia/500/01(H5N3)hemagglutinin (HA)
AB241621.1


A/duck/Primorie/2633/01(H5N3) matrix protein (M1)
AJ621810.1


A/duck/Primorie/2633/01(H5N3)nucleoprotein (NP)
AJ621808.1


A/duck/Primorie/2633/01(H5N3)hemagglutinin (HA)
AJ621807.1


A/duck/Primorie/2633/01(H5N3)nucleoprotein (NP)
AJ621809.1


A/goose/Hong Kong/23/78(H5N3) matrix protein 1 (M) and matrix
DQ107454.1


protein 2 (M)



A/mallard/Wisconsin/169/75(H5N3) hemagglutinin
U79452.1


A/swan/Hokkaido/51/96(H5N3)hemagglutinin (HA)
AB241617.1


A/swan/Hokkaido/4/96(H5N3) hemagglutinin (HA)
AB241616.1


A/turkey/CA/6878/79(H5N3) matrix protein 1 (M) and matrix
DQ107469.1


protein 2 (M)



A/tern/South Africa/61(H5N3) hemagglutinin precursor (HA)
U20460.1


A/gull/Delaware/5/2000(H5N4) matrix protein 1 (M) and matrix
DQ107459.1


protein 2 (M)



A/gull/Delaware/4/2000(H5N4) matrix protein 1 (M) and matrix
DQ107458.1


protein 2 (M)



A/shorebird/Delaware/109/2000(H5N4) matrix protein 1 (M)
DQ107460.1


A/shorebird/Delaware/243/2000(H5N4) matrix protein 1 (M) and
DQ107462.1


matrix protein 2 (M)



A/shorebird/Delaware/230/2000(H5N4) matrix protein 1 (M) and
DQ107461.1


matrix protein 2 (M)



A/mallard/Wisconsin/34/75(H5N6) hemagglutinin
U79451.1


A/duck/Potsdam/2216-4/1984(H5N6) hemagglutinin H5
AF082041.1


A/shorebird/Delaware/207/98 (H5N8) nonfunctional matrix protein
AY664456.1


A/shorebird/Delaware/27/98 (H5N8) nonfunctional matrix protein
AY664453.1


A/herring gull/Delaware/281/98 (H5N8) nonfunctional matrix
AY664452.1


protein



A/mallard/Ohio/556/1987(H5N9) hemagglutinin (HA)
U67783.2


A/turkey/Wisconsin/68(H5N9) hemagglutinin
U79456.1


A/blue-winged teal/Alberta/685/82(H6N1) matrix protein 1 (M)
DQ107448.1


and matrix protein 2 (M)



A/chicken/Taiwan/7-5/99(H6N1) nucleocapsid protein (NP)
AF261750.1


A/chicken/Taiwan/7-5/99(H6N1) matrix protein
AF262213.1


A/chicken/Taiwan/7-5/99(H6N1) nonstructural protein
AF262212.1


A/chicken/Taiwan/7-5/99(H6N1) polymerase (PA)
AF262211.1


A/chicken/Taiwan/7-5/99(H6N1) polymerase subunit PB1
AF262210.1


A/chicken/Taiwan/7-5/99(H6N1) nucleocapsid protein (NP)
AF261750.1


A/chicken/Taiwan/ns2/99(H6N1) segment 4 hemagglutinin (HA1)
AF310985.1


A/chicken/Taiwan/na3/98(H6N1) segment 4 hemagglutinin (HA1)
AF310984.1


A/chicken/Taiwan/7-5/99(H6N1) segment 4 hemagglutinin (HA1)
AF310983.1


A/duck/Hong Kong/D73/76(H6N1) matrix protein 1 (M) and matrix
DQ107432.1


protein 2 (M)



A/duck/Taiwan/9/23-3/2000(H6N1) matrix protein 1 (M) and matrix
DQ107407.1


protein 2 (M)



A/pheasant/Hong Kong/FY479/2000(H6N1) matrix protein 1 (M) and
DQ107409.1


matrix protein 2 (M)



A/pheasant/Hong Kong/SSP44/2002(H6N1) matrix protein 1 (M) and
DQ107412.1


matrix protein 2 (M)



A/quail/Hong Kong/YU421/2002(H6N1) matrix protein 1 (M) and
DQ107414.1


matrix protein 2 (M)



A/avian/NY/17150-7/2000(H6N2) matrix protein 1 (M) and matrix
DQ107423.1


protein 2 (M)



A/chicken/CA/285/2003(H6N2) matrix protein 1 (M) and matrix
DQ107429.1


protein 2 (M)



A/chicken/CA/375TR/2002(H6N2) matrix protein 1 (M) and matrix
DQ107428.1


protein 2 (M)



A/chicken/CA/203/2003(H6N2) matrix protein 1 (M) and matrix
DQ107426.1


protein 2 (M)



A/chicken/NY/101250-7/2001(H6N2) matrix protein 1 (M) and
DQ107419.1


matrix protein 2 (M)



A/chicken/CA/625/2002(H6N2) matrix protein 1 (M) and matrix
DQ107418.1


protein 2 (M)



A/Chicken/California/0139/2001(H6N2)nucleoprotein (NP)
AF474070.1


A/Chicken/California/650/2000(H6N2) nucleoprotein (NP)
AF474069.1


A/Chicken/California/9420/2001(H6N2) neuraminidase N2 (N2)
AF474048.1


A/Chicken/California/9174/2001(H6N2) neuraminidase N2 (N2)
AF474047.1


A/Chicken/California/8892/2001(H6N2)neuraminidase N2 (N2)
AF474046.1


A/Chicken/California/6643/2001(H6N2) neuraminidase N2 (N2)
AF474045.1


A/Chicken/California/1316/2001(H6N2)neuraminidase N2 (N2)
AF474044.1


A/Chicken/California/0139/2001(H6N2) neuraminidase N2 (N2)
AF474043.1


A/Chicken/California/1002/2000(H6N2) neuraminidase N2 (N2)
AF474042.1


A/Chicken/California/650/2000(H6N2) neuraminidase N2 (N2)
AF474041.1


A/Chicken/California/465/2000(H6N2) neuraminidase N2 (N2)
AF474040.1


A/Chicken/California/431/2000(H6N2) neuraminidase N2 (N2)
AF474039.1


A/Chicken/California/6643/2001(H6N2) hemagglutinin H6 (H6)
AF474035.1


A/Chicken/California/431/2000(H6N2) hemagglutinin H6 (H6)
AF474029.1


A/Chicken/California/9420/2001(H6N2) hemagglutinin H6 (H6)
AF474038.1


A/Chicken/California/9174/2001(H6N2) hemagglutinin H6 (H6)
AF474037.1


A/Chicken/California/8892/2001(H6N2) hemagglutinin H6 (H6)
AF474036.1


A/Chicken/California/1316/2001(H6N2) hemagglutinin H6 (H6)
AF474034.1


A/Chicken/California/0139/2001(H6N2) hemagglutinin H6 (H6)
AF474033.1


A/Chicken/California/1002/2000(H6N2) hemagglutinin H6 (H6)
AF474032.1


A/Chicken/California/650/2000(H6N2) hemagglutinin H6 (H6)
AF474031.1


A/Chicken/California/465/2000(H6N2) hemagglutinin H6 (H6)
AF474030.1


A/cornish cross/CA/139/2001(H6N2) matrix protein 1 (M) and
DQ107424.1


matrix protein 2 (M)



A/duck/Eastern China/164/2002(H6N2) segment 6 neuraminidase
EU429762.1


(NA)



A/duck/Eastern China/729/2003(H6N2) segment 6 neuraminidase
EU429760.1


(NA)



A/duck/Eastern China/262/2002(H6N2) segment 6 neuraminidase
EU429743.1


(NA)



A/duck/Eastern China/74/2006(H6N2) segment 6 neuraminidase
EU429741.1


(NA)



A/duck/Eastern China/161/2002(H6N2) segment 6 neuraminidase
EU429740.1


(NA)



A/duck/Hong Kong/960/80(H6N2)) matrix protein 1 (M) and matrix
DQ107435.1


protein 2 (M)



A/duck/Hong Kong/D134/77(H6N2)) matrix protein 1 (M) and matrix
DQ107433.1


protein 2 (M)



A/duck/CA/10221/2002(H6N2) matrix protein 1 (M) and matrix
DQ107421.1


protein 2 (M)



A/duck/Shantou/5540/2001(H6N2) matrix protein 1 (M) and matrix
DQ107431.1


protein 2 (M)



A/guinea fowl/Hong Kong/SSP99/2002(H6N2) matrix protein 1 (M)
DQ107413.1


and matrix protein 2 (M)



A/mallard/NY/016/83(H6N2) matrix protein 1 (M) and matrix
DQ107449.1


protein 2 (M)



A/mallard/NY/046/83(H6N2) matrix protein 1 (M) and matrix
DQ107450.1


protein 2 (M)



A/pintail/Alberta/644/81(H6N2) matrix protein 1 (M) and matrix
DQ107445.1


protein 2 (M)



A/quail/Hong Kong/SF792/2000(H6N2) matrix protein 1 (M) and
DQ107410.1


matrix protein 2 (M)



A/ruddy turnstone/Delaware/106/98 (H6N2) nonfunctional matrix
AY664439.1


protein



A/Shorebird/Delaware/127/97(H6N2) nonfunctional matrix protein
AY664467.1


A/shorebird/Delaware/124/2001(H6N2) matrix protein 1 (M) and
DQ107417.1


matrix protein 2 (M)



A/shorebird/Delaware/208/2001(H6N2) matrix protein 1 (M) and
DQ107427.1


matrix protein 2 (M)



A/turkey/CA/527/2002(H6N2) matrix protein 1 (M) and matrix
DQ107420.1


protein 2 (M)



A/turkey/CA/1623CT/2002(H6N2) matrix protein 1 (M) and matrix
DQ107425.1


protein 2 (M)



A/turkey/MN/836/80(H6N2) matrix protein 1 (M) and matrix
DQ107440.1


protein 2 (M)



A/turkey/MN/735/79(H6N2) matrix protein 1 (M) and matrix
DQ107437.1


protein 2 (M)



A/chicken/Hong Kong/17/77(H6N4)) matrix protein 1 (M) and
DQ107436.1


matrix protein 2 (M)



A/chicken/Hong Kong/CSW106/2001(H6N4) matrix protein 1 (M) and
DQ107406.1


matrix protein 2 (M)



A/gull/Delaware/18/2000(H6N4) matrix protein 1 (M) and matrix
DQ107415.1


protein 2 (M)



A/pheasant/Hong Kong/CSW2573/2001(H6N4) matrix protein 1 (M)
DQ107411.1


and matrix protein 2 (M)



A/quail/Hong Kong/CSW106/2001(H6N4) matrix protein 1 (M) and
DQ107430.1


matrix protein 2 (M)



A/Shorebird/Delaware/194/98(H6N4) nonfunctional matrix protein
AY664424.1


A/shorebird/Delaware/259/2000(H6N4) matrix protein 1 (M) and
DQ107416.1


matrix protein 2 (M)



A/shearwater/Australia/1/1972(H6N5) segment 6 neuraminidase
EU429794.1


(NA)



A/shearwater/Australia/1/1972(H6N5) polymerase A (PA)
L25832.1


A/pintail/Alberta/1040/79(H6N5) matrix protein 1 (M) and matrix
DQ107439.1


protein 2 (M)



A/blue-winged teal/MN/993/80(H6N6)) matrix protein 1 (M) and
DQ107441.1


matrix protein 2 (M)



A/duck/NY/83779/2002(H6N6) matrix protein 1 (M) and matrix
DQ107422.1


protein 2 (M)



A/duck/MN/1414/81(H6N6) matrix protein 1 (M) and matrix
DQ107444.1


protein 2 (M)



A/mallard/Alberta/289/82(H6N6) matrix protein 1 (M) and matrix
DQ107447.1


protein 2 (M)



A/mallard duck/MN/1041/80(H6N6) matrix protein 1 (M) and matrix
DQ107442.1


protein 2 (M)



A/pintail/Alberta/189/82(H6N6) matrix protein 1 (M) and matrix
DQ107446.1


protein 2 (M)



A/sanderling/Delaware/1258/86(H6N6) nonfunctional matrix
AY664436.1


protein



A/blue-winged teal/Alberta/368/78(H6N8)) matrix protein 1 (M)
DQ107438.1


and matrix protein 2 (M)



A/ruddy turnstone/Delaware/105/98 (H6N8) nonfunctional matrix
AY664428.1


protein



A/domestic duck/NY/81(H6N8)) matrix protein (M)
DQ107443.1


A/duck/Eastern China/163/2002(H6N8) segment 6 neuraminidase
EU429786.1


(NA)



A/duck/Hong Kong/D182/77(H6N9) matrix protein 1 (M) and matrix
DQ107434.1


protein 2 (M)



A/chicken/Hong Kong/SF3/2001(H6) matrix protein 1 (M) and
DQ107408.1


matrix protein 2 (M)



A/African starling/England/983/79(H7N1) neuraminidase (N1)
AJ416629.1


A/Afri.Star./Eng-Q/938/79(H7N1) hemagglutinin precurosr
AF149295.1


A/chicken/Italy/1067/99(H7N1) matrix protein 1 (M1)
AJ416630.1


A/chicken/Italy/1067/99(H7N1) neuraminidase (N1)
AJ416627.1


A/chicken/Italy/4575/99 (H7N1) hemagglutinin (HA)
AJ493469.1


A/chicken/Italy/13474/99(H7N1) haemagglutinin (HA)
AJ491720.1


A/chicken/Italy/445/1999(H7N1)
AX537385.1


A/Chicken/Italy/267/00(H7N1) hemagglutinin (HA)
AJ493215.1


A/Chicken/Italy/13489/99(H7N1) hemagglutinin (HA)
AJ493214.1


A/Chicken/Italy/13307/99(H7N1) hemagglutinin (HA)
AJ493212.1


A/chicken/Singapore/1994(H7N1) M2 protein
EU014140.1


A/duck/Hong Kong/301/78(H7N1) matrix protein 1 (M) and matrix
DQ107475.1


protein 2 (M)



A/Hong Kong/301/78(H7N1) hemagglutinin (HA)
AY672090.1


A/fowl plaguq virus/Rostock/34 (H7N1) NP protein
AJ243993.1


A/fowl plaguq virus/Rostock/34 (H7N1) PA protein
AJ243992.1


A/fowl plaguq virus/Rostock/34 (H7N1) PB2 protein
AJ243991.1


A/fowl plaguq virus/Rostock/34 (H7N1) PB1 protein
AJ243990.1


A/ostrich/South Africa/5352/92(H7N1) hemagglutinin precursor
U20458.1


(HA)



A/rhea/North Carolina/39482/93(H7N1) hemagglutinin precursor
U20468.1


(HA)



A/turkey/Italy/3775/99 (H7N1) hemagglutinin (HA)
AJ493472.1


A/turkey/Italy/4603/99 (H7N1) hemagglutinin (HA)
AJ493471.1


A/turkey/Italy/4602/99 (H7N1) hemagglutinin (HA)
AJ493470.1


A/turkey/Italy/4169/99 (H7N1) hemagglutinin (HA)
AJ493468.1


A/turkey/Italy/4073/99 (H7N1) hemagglutinin (HA)
AJ493467.1


A/turkey/Italy/3889/99 (H7N1) hemagglutinin (HA)
AJ493466.1


A/turkey/Italy/12598/99(H7N1) haemagglutinin (HA)
AJ489520.1


A/turkey/Italy/4580/99(H7N1) haemagglutinin (HA)
AJ416628.1


A/Turkey/Italy/335/00(H7N1) haemagglutinin (HA)
AJ493217.1


A/Turkey/Italy/13468/99(H7N1) haemagglutinin (HA)
AJ493216.1


A/Turkey/Italy/13467/99(H7N1) haemagglutinin (HA)
AJ493213.1


A/chicken/CT/9407/2003(H7N2) matrix protein 1 (M) and matrix
DQ107478.1


protein 2 (M)



A/chicken/NY/116124/2003(H7N2) matrix protein 1 (M) and matrix
DQ107479.1


protein 2 (M)



A/chicken/PA/143586/2002(H7N2) matrix protein 1 (M) and matrix
DQ107477.1


protein 2 (M)



A/duck/Hong Kong/293/78(H7N2) matrix protein 1 (M) and matrix
DQ107474.1


protein 2 (M)



A/duck/Hong Kong/293/78(H7N2) hemagglutinin precursor (HA)
U20461.1


A/laughing gull/Delaware/2838/87 (H7N2) nonfunctional matrix
AY664427.1


protein



A/pheasant/NJ/30739-9/2000(H7N2) matrix protein 1 (M) and
DQ107481.1


matrix protein 2 (M)



A/ruddy turnstone/Delaware/130/99 (H7N2) onfunctional matrix
AY664451.1


protein



A/unknown/149717-12/2002(H7N2) matrix protein 1 (M) and matrix
DQ107480.1


protein 2 (M)



A/unknown/NY/74211-5/2001(H7N2) matrix protein 1 (M) and matrix
DQ107476.1


protein 2 (M)



A/unknown/149717-12/2002(H7N2) matrix protein 1 (M) and matrix
DQ107480.1


protein 2(M)



A/unknown/NY/74211-5/2001(H7N2) matrix protein 1(M) and matrix
DQ107476.1


protein 2 (M)



A/chicken/British Columbia/CN7-3/04 (H7N3) hemagglutinin (HA)
AY644402.1


A/chicken/British Columbia/CN7-3/04 (H7N3) matrix protein (M1)
AY677732.1


A/chicken/Italy/270638/02(H7N3) hemagglutinin (HA)
EU158111.1


A/gadwall/MD/3495/83(H7N3) matrix protein 1 (M) and matrix
DQ107488.1


protein 2 (M)



A/mallard/Alberta/22/2001(H7N3) matrix protein 1 (M) and matrix
DQ107482.1


protein 2 (M)



A/mallard/Alberta/699/81(H7N3) matrix protein 1 (M) and matrix
DQ107487.1


protein 2 (M)



A/pintail/Alberta/25/2001(H7N3) matrix protein 1 (M) and matrix
DQ107483.1


protein 2 (M)



A/Quail/Arkansas/16309-7/94 (H7N3) hemagglutinin protein
AF072401.1


subunit 1 precursor (HA1)



A/ruddy turnstone/New Jersey/65/85(H7N3) nonfunctional matrix
AY664433.1


protein



A/turkey/England/63(H7N3) hemagglutinin precursor (HA)
U20462.1


A/Turkey/Colorado/13356/91 (H7N3) hemagglutinin protein subunit
AF072400.1


1 precursor (HA1)



A/turkey/MN/1200/80(H7N3)) matrix protein 1 (M) and matrix
DQ107486.1


protein 2 (M)



A/turkey/MN/1818/82(H7N3) matrix protein 1 (M) and matrix
DQ107489.1


protein 2 (M)



A/turkey/Minnesota/1237/80(H7N3) hemagglutinin precursor (HA)
U20466.1


A/turkey/TX/1/79(H7N3) matrix protein 1 (M) and matrix protein
DQ107484.1


2 (M)



A/Turkey/Oregon/71(H7N3) hemagglutinin
AF497557.1


A/Turkey/Utah/24721-10/95 (H7N3) hemagglutinin protein subunit
AF072402.1


1 precursor (HA1)



A/softbill/South Africa/142/92(H7N4) hemagglutinin precursor
U20464.1


(HA)



A/ruddy turnstone/Delaware/2770/87 (H7N5) nonfunctional matrix
AY664476.1


protein



A/chicken/Brescia/1902(H7N7) hemagglutinin 1 chain (HA)
U20471.1


A/chicken/Jena/1816/87(H7N7) hemagglutinin precursor (HA)
U20469.1


A/chicken/Leipzig/79(H7N7) hemagglutinin precursor (HA)
U20459.1


A/duck/Heinersdorf/S495/6/86(H7N7) hemagglutinin precursor (HA)
U20465.1


A/equine/Prague/1/56 (H7N7) neuraminidase
U85989.1


A/equine/Santiago/77(H7N7) nucleoprotein
AY383752.1


A/equine/Santiago/77(H7N7) neuraminidase
AY383757.1


A/equine/Santiago/77(H7N7) hemagglutinin
AY383756.1


A/FPV/Weybridge(H7N7) matrix protein
M38299.1


A/goose/Leipzig/187/7/1979(H7N7) hemagglutinin
L43914.1


A/goose/Leipzig/192/7/1979(H7N7) hemagglutinin
L43915.1


A/goose/Leipzig/137/8/1979(H7N7) hemagglutinin
L43913.1


A/ruddy turnstone/Delaware/134/99 (H7N7) nonfunctional matrix
AY664468.1


protein



A/seal/Mass/1/80 H7N7 recombinant
S73497.1


A/swan/Potsdam/63/6/81(H7N7) hemagglutinin precursor (HA)
U20467.1


A/tern/Potsdam/342/6/79(H7N7) hemagglutinin precursor (HA)
U20470.1


A/pintail/Alberta/121/79(H7N8) matrix protein 1 (M) and matrix
DQ107485.1


protein 2 (M)



A/Turkey/Minnesota/38429/88(H7N9) hemagglutinin
AF497551.1


A/turkey/Ontario/6118/1968(H8N4) segment 6 neuraminidase (NA)
EU429793.1


A/Mallard Duck/Alberta/357/84(H8N4) segment 4 hemagglutinin
AF310988.1


(HA1)



A/Pintail Duck/Alberta/114/79(H8N4) segment 4 hemagglutinin
AF310987.1


(HA1)



A/duck/Eastern China/01/2005(H8N4) segment 6 neuraminidase (NA)
EU429780.1


A/Red Kont/Delaware/254/94(H8N4) segment 4 hemagglutinin (HA1)
AF310989.1


A/chicken/Amioz/1527/03(H9N2) nucleoprotein
DQ116511.1


A/chicken/Amioz/1527/03(H9N2) neuraminidase
DQ116081.1


A/chicken/Amioz/1527/03(H9N2) hemagglutinin
DQ108911.1


A/chicken/Alonim/1953/104(H9N2) hemagglutinin
DQ108928.1


A/chicken/Alonim/1552/03(H9N2) hemagglutinin
DQ108914.1


A/chicken/Alonim/1552/03(H9N2) nucleoprotein
DQ116514.1


A/chicken/Alonim/1965/04(H9N2) hemagglutinin
DQ108929.1


A/Chicken/Anhui/1/98(H9N2) hemagglutinin (HA)
AF461511.1


A/Chicken/Beijing/1/95(H9N2) nonfunctional matrix protein
AF536719.1


A/Chicken/Beijing/1/95(H9N2) nucleoprotein (NP)
AF536699.1


A/Chicken/Beijing/1/95(H9N2) nonfunctional nonstructural
AF536729.1


protein



A/Chicken/Beijing/1/95(H9N2) segment 6 neuraminidase (NA)
AF536709.1


A/Chicken/Beijing/2/97(H9N2) nucleoprotein (NP)
AF536700.1


A/Chicken/Beijing/2/97(H9N2) nonfunctional matrix protein
AF536720.1


A/Chicken/Beijing/2/97(H9N2) nonfunctional nonstructural
AF536730.1


protein



A/Chicken/Beijing/2/97(H9N2) segment 6 neuraminidase (NA)
AF536710.1


A/Chicken/Beijing/1/97(H9N2) hemagglutinin (HA)
AF461530.1


A/Chicken/Beijing/3/99(H9N2) nonfunctional matrix protein
AF536721.1


A/Chicken/Beijing/3/99(H9N2) nucleoprotein (NP)
AF536701.1


A/Chicken/Beijing/3/99(H9N2) nonfunctional nonstructural
AF536731.1


protein



A/Chicken/Beijing/3/99(H9N2) segment 6 neuraminidase (NA)
AF536711.1


A/chicken/Beit Alfa/1282/03(H9N2)hemagglutinin
DQ104476.1


A/chicken/Beit-Aran/29/05(H9N2) hemagglutinin
DQ108931.1


A/chicken/Bnei Darom/1557/03(H9N2) hemagglutinin
DQ108915.1


A/chicken/Ein Habsor/1808/04(H9N2) hemagglutinin
DQ108925.1


A/Chicken/Gangxi/2/00(H9N2) hemagglutinin (HA)
AF461514.1


A/Chicken/Gangxi/1/00(H9N2) hemagglutinin (HA)
AF461513.1


A/chicken/Gan Shomron/1465/03(H9N2) hemagglutinin
DQ104480.1


A/chicken/Gan Shomron/1292/03(H9N2) hemagglutinin
DQ104478.1


A/chicken/Gan_Shomron/1465/03(H9N2) nucleoprotein
DQ116506.1


A/chicken/Gan_Shomron/1465/03(H9N2) neuraminidase
DQ116077.1


A/chicken/Gan Shomron/1543/04(H9N2) nucleoprotein
DQ116512.1


A/chicken/Gan Shomron/1543/04(H9N2) hemagglutinin
DQ108912.1


A/Chicken/Guangdong/97(H9N2) nonfunctional matrix protein
AF536722.1


A/Chicken/Guangdong/97(H9N2) nucleoprotein (NP)
AF536702.1


A/Chicken/Guangdong/97(H9N2) nonfunctional nonstructural
AF536732.1


protein



A/Chicken/Guangdong/97(H9N2) segment 6 neuraminidase (NA)
AF536712.1


A/Chicken/Gansu/1/99(H9N2) hemagglutinin (HA)
AF461512.1


A/chicken/Gujrat/India/3697/2004(H9N2) polymerase basic 2
DQ979865.1


(PB2)



A/chicken/Haryana/India/2424/2004(H9N2) polymerase basic 2
DQ979862.1


(PB2)



A/Chicken/Henan/98(H9N2) nonfunctional matrix protein
AF536726.1


A/Chicken/Henan/98(H9N2) nucleoprotein (NP)
AF536706.1


A/Chicken/Henan/98(H9N2) nonfunctional nonstructural protein
AF536736.1


A/Chicken/Henan/2/98(H9N2) hemagglutinin (HA)
AF461517.1


A/Chicken/Henan/1/99(H9N2) hemagglutinin (HA)
AF461516.1


A/Chicken/Henan/98(H9N2) segment 6 neuraminidase (NA)
AF536716.1


A/Chicken/Hebei/1/96(H9N2) nonfunctional matrix protein
AF536723.1


A/Chicken/Hebei/1/96(H9N2) segment 6 nonfunctional
AF536713.1


neuraminidase protein



A/Chicken/Hebei/1/96(H9N2) nucleoprotein (NP)
AF536703.1


A/Chicken/Hebei/1/96(H9N2) nonfunctional nonstructural protein
AF536733.1


A/Chicken/Hebei/1/96(H9N2) segment 6 nonfunctional
AF536713.1


neuraminidase protein



A/Chicken/Hebei/2/00(H9N2) hemagglutinin (HA)
AF461531.1


A/Chicken/Hebei/2/98(H9N2) nonfunctional matrix protein
AF536724.1


A/Chicken/Hebei/2/98(H9N2) nucleoprotein (NP)
AF536704.1


A/Chicken/Hebei/2/98(H9N2) nonfunctional nonstructural protein
AF536734.1


A/Chicken/Hebei/2/98(H9N2) segment 6 neuraminidase (NA)
AF536714.1


A/Chicken/Hebei/1/00(H9N2) hemagglutinin (HA)
AF461515.1


A/Chicken/Hebei/3/98(H9N2) nucleoprotein (NP)
AF536705.1


A/Chicken/Hebei/3/98(H9N2) nonfunctional matrix protein
AF536725.1


A/Chicken/Hebei/3/98(H9N2) nonfunctional onstructural protein
AF536735.1


A/Chicken/Hebei/3/98(H9N)) segment 6 neuraminidase (NA)
AF536715.1


A/chicken/Hong Kong/FY313/2000(H9N2) matrix protein 1 (M) and
DQ107508.1


matrix protein 2 (M)



A/chicken/Hong Kong/WF208/2001(H9N2) matrix protein 1 (M) and
DQ107513.1


matrix protein 2 (M)



A/chicken/Hong Kong/NT471/2002(H9N2) matrix protein 1 (M) and
DQ107514.1


matrix protein 2 (M)



A/chicken/Hong Kong/WF2/99(H9N2) hemagglutinin
AY206677.1


A/chicken/Iarah/1376/03(H9N2) nucleoprotein
DQ116504.1


A/chicken/Iarah/1376/03(H9N2) neuraminidase
DQ116075.1


A/chicken/Iarah/1376/03(H9N2) hemagglutinin
DQ108910.1


A/chicken/India/2793/2003(H9N2) hemagglutinin (HA)
AY336597.1


A/chicken/Iran/101/1998(H9N2) matrix protein 2 (M2)
EU477375.1


A/Chicken/Jiangsu/1/99(H9N)) hemagglutinin (HA)
AF461509.1


A/Chicken/Jiangsu/2/98(H9N2) hemagglutinin (HA)
AF461510.1


A/chicken/Kfar Monash/636/02(H9N2) hemagglutinin
DQ104464.1


A/chicken/Kalanit/1966/06.12.04(H9N2) hemagglutinin
DQ108930.1


A/chicken/Kaianit/1946/04(H9N2) hemagglutinin
DQ108927.1


A/chicken/Korea/S4/2003(H9N2) matrix protein 1 (M) and matrix
DQ107517.1


protein 2 (M)



A/Chicken/Korea/MS96/96(H9N2) matrix protein 1 and 2 (M)
AF203788.1


A/Chicken/Korea/MS96/96(H9N2) neuraminidase subtype 2
AF203786.1


A/Chicken/Korea/MS96/96(H9N2) nucleoprotein
AF203787.1


A/Chicken/Liaoning/99(H9N2) nonfunctional matrix protein
AF536727.1


A/Chicken/Liaoning/1/00(H9N2) hemagglutinin (HA)
AF461518.1


A/Chicken/Liaoning/99(H9N2) nucleoprotein (NP)
AF536707.1


A/Chicken/Liaoning/99(H9N2) nonfunctional matrix protein
AF536727.1


A/Chicken/Liaoning/99(H9N2) nonfunctional onstructural protein
AF536737.1


A/Chicken/Liaoning/2/00(H9N2) hemagglutinin (HA)
AF461519.1


A/chicken/Liaoning/99(H9N2) segment 6 neuraminidase (NA)
AF536717.1


A/chicken/Mudanjiang/0823/2000(H9N2) nucleoprotein (NP)
AY496851.1


A/Chicken/Mudanjiang/0823/2000 (H9N2) nonstructural protein
AY631868.1


A/Chicken/Mudanjiang/0823/00 (H9N2) hemagglutinin (HA)
AY513715.1


A/chicken/Mudanjiang/0823/2000(H9N2) matrix protein (M1)
AY496852.1


A/chicken/Mudanjiang/0823/2000(H9N2) nucleoprotein (np)
AY496851.1


A/chicken/Maale HaHamisha/90658/00(H9N2) hemagglutinin
DQ104472.1


A/chicken/Maanit/1477/03(H9N2) hemagglutinin
DQ104483.1


A/chicken/Maanit/1291/03(H9N2) hemagglutinin
DQ104477.1


A/chicken/Maanit/1275/03(H9N2) hemagglutinin
DQ104457.1


A/chicken/Maanit/1477/03(H9N2) nucleoprotein
DQ116508.1


A/chicken/Netohah/1373/03 (H9N2) nucleoprotein
DQ116503.1


A/chicken/Netohah/1373/03 (H9N2) neuraminidase
DQ116074.1


A/chicken/Netohah/1373/03 (H9N2) hemagglutinin
DQ108909.1


A/chicken/Neve Ilan/1504/03(H9N2) hemagglutinin
DQ104484.1


A/chicken/Neve_Ilan/1504/03(H9N2) nucleoprotein
DQ116509.1


A/chicken/Neve_Ilan/1504/03(H9N2) neuraminidase
DQ116079.1


A/chicken/Orissa/India/2317/2004(H9N2) polymerase basic 2 (PB2)
DQ979861.1


A/chicken/Pardes-Hana-Carcur/1475/03(H9N2) hemagglutinin
DQ104482.1


A/chicken/Pardes-Hana-Carcur/1475/03(H9N2) neuraminidase
DQ116078.1


A/chicken/Saar/1456/03(H9N2) hemagglutinin
DQ104479.1


A/chicken/Sde_Uziahu/1747/04(H9N2) neuraminidase
DQ116068.1


A/chicken/Sede Uzziyyahu/1651/04(H9N2) hemagglutinin
DQ108923.1


A/chicken/Sde Uziahu/1747/04(H9N2)
DQ108905.1


A/chicken/Singapore/1998(H9N2) M2 protein
EU014142.1


A/chicken/Singapore/1998(H9N2) M2 protein
EU014142.1


A/Chicken/Shandong/98(H9N2) nonfunctional matrix protein
AF536728.1


A/Chicken/Shandong/1/98(H9N2) hemagglutinin (HA)
AF461520.1


A/Chicken/Shandong/98(H9N2) nucleoprotein (NP)
AF536708.1


A/Chicken/Shandong/98(H9N2) nonfunctional nonstructural protein
AF536738.1


A/Chicken/Shandong/98(H9N2) segment 6 neuraminidase (NA)
AF536718.1


A/Chicken/Shandong/2/99(H9N2) hemagglutinin (HA)
AF461521.1


A/chicken/Shandong/1/02(H9N2) neuraminidase (NA)
AY295761.1


A/Chicken/Shanghai/F/98(H9N2) hemagglutinin
AF461532.1


A/Chicken/Shanghai/1/02(H9N2) hemagglutinin
AY281745.1


A/Chicken/Shanghai/2/99(H9N2)) hemagglutinin (HA)
AF461522.1


A/Chicken/Shanghai/3/00(H9N2)) hemagglutinin (HA)
AF461523.1


A/Chicken/Shanghai/F/98(H9N2) hemagglutinin (HA)
AY743216.1


A/Chicken/Shanghai/4-2/01(H9N2) hemagglutinin (HA)
AF461525.1


A/Chicken/Shanghai/4-1/01(H9N2) hemagglutinin (HA)
AF461524.1


A/Chicken/Shanghai/4/01(H9N2) hemagglutinin (HA)
AY083841.1


A/Chicken/Shanghai/3/01(H9N2) hemagglutinin HA)
AY083840.1


A/chicken/Talmei_Elazar/1304/03(H9N2)nucleoprotein
DQ116530.1


A/chicken/Talmei_Elazar/1304/03(H9N2) neuraminidase
DQ116072.1


A/Chicken/Tianjing/2/96(H9N2) hemagglutinin
AF461527.1


A/Chicken/Tianjing/1/96(H9N2) hemagglutinin (HA)
AF461526.1


A/chicken/Tel Adashim/811/01 (H9N2) hemagglutinin
DQ104467.1


A/chicken/Tel Adashim/811/01 (H9N2) nucleoprotein
DQ116527.1


A/ck/Tel_Adashim/811/01(H9N2) neuraminidase
DQ116064.1


A/chicken/Tel Adashim/812/01 (H9N2) nucleoprotein
DQ116528.1


A/chicken/Tel Adashim/812/01 (H9N2) hemagglutinin
DQ104468.1


A/ck/Tel_Adashim/812/01(H9N2) neuraminidase
DQ116065.1


A/chicken/Tel Adashim/786/01 (H9N2) nucleoprotein
DQ116524.1


A/chicken/Tel Adashim/809/01 (H9N2) hemagglutinin
DQ104465.1


A/chicken/Tel Adashim/809/01 (H9N2) nucleoprotein
DQ116525.1


A/chicken/Tel Adashim/1469/03 (H9N2) nucleoprotein
DQ116507.1


A/chicken/Tel Adashim/1469/303(H9N2) hemagglutinin
DQ104481.1


A/chicken/Tel Adashim/1506/03 (H9N2) neuraminidase
DQ116080.1


A/chicken/Tel Adashim/1506/03(H9N2) hemagglutinin
DQ104474.1


A/chicken/Tel Adashim/1506/03 (H9N2) nucleoprotein
DQ116510.1


A/chicken/Tel Adashim/1332/03(H9N2) nucleoprotein
DQ116501.1


A/chicken/Tel Adashim/1321/03(H9N2) nucleoprotein
DQ116500.1


A/chicken/Tel Adashim/1332/03(H9N2) hemagglutinin
DQ108907.1


A/chicken/Tel Adashim/1321/03(H9N2) hemagglutinin
DQ108906.1


A/chicken/Telmond/1308/03(H9N2) nucleoprotein
DQ116499.1


A/chicken/Telmond/1308/03(H9N2) neuraminidase
DQ116073.1


A/chicken/Telmond/1308/03(H9N2) hemagglutinin
DQ108921.1


A/chicken/Tzrofa/1568/04(H9N2) nucleoprotein
DQ116519.1


A/chicken/Tzrofa/1568/04(H9N2) hemagglutinin
DQ108919.1


A/chicken/UP/India/2544/2004(H9N2) polymerase basic 2 (PB2)
DQ979864.1


A/chicken/UP/India/2543/2004(H9N2) polymerase basic 2 (PB2)
DQ979863.1


A/chicken/Wangcheng/4/2001(H9N2) nucleoprotein
AY268949.1


A/chicken/Ysodot/1362/03(H9N2) nucleoprotein
DQ116502.1


A/chicken/Ysodot/1362/03(H9N2) hemagglutinin
DQ108908.1


A/Chicken/Yunnan/2/00(H9N2) hemagglutinin (HA)
AF461529.1


A/Chicken/Yunnan/1/99(H9N2) hemagglutinin (HA)
AF461528.1


A/duck/Eastern China/01/2000(H9N2) segment 6 neuraminidase (NA)
EU429725.1


A/duck/Eastern China/48/2001(H9N2) segment 6 neuraminidase (NA)
EU429707.1


A/duck/Eastern China/66/2003(H9N2) segment 6 neuraminidase (NA)
EU429699.1


A/duck/Eastern China/80/2004(H9N2) segment 6 neuraminidase (NA)
EU429726.1


A/duck/Hong Kong/448/78(H9N2) matrix protein 1 (M) and matrix
DQ107494.1


protein 2 (M)



A/duck/Hong Kong/448/78(H9N2) hemagglutinin precursor
AY206673.1


A/duck/Hong Kong/366/78(H9N2) hemagglutinin precursor
AY206674.1


A/duck/Hong Kong/784/79(H9N2)) matrix protein 1(M) and matrix
DQ107496.1


protein 2 (M)



A/duck/Hong Kong/702/79(H9N2) matrix protein 1 (M) and matrix
DQ107495.1


protein 2 (M)



/duck/Hong Kong/702/79(H9N2) hemagglutinin precursor
AY206672.1


A/duck/Hong Kong/610/79(H9N2) hemagglutinin precursor
AY206680.1


A/duck/Hong Kong/552/79(H9N2) hemagglutinin precursor
AY206679.1


A/duck/Hong Kong/644/79(H9N2) hemagglutinin precursor
AY206678.1


A/duck/Korea/S13/2003(H9N2) matrix protein 1 (M) and matrix
DQ107518.1


protein 2 (M)



A/duck/Nanchang/4-361/2001(H9N2) matrix protein 1 (M) and
DQ107511.1


matrix protein 2 (M)



A/duck/NY/83793/2002(H9N2) matrix protein 1 (M) and matrix
DQ107499.1


protein 2 (M)



A/goose/MN/5733-1243/80(H9N2) matrix protein 1 (M) and matrix
DQ107492.1


protein 2 (M)



A/geese/Tel Adashim/829/01(H9N2) hemagglutinin
DQ104469.1


A/geese/Tel Adashim/830/01(H9N2 hemagglutinin
DQ104470.1


A/ostrich/Eshkol/1436/03(H9N2) neuraminidase
DQ116076.1


A/ostrich/Eshkol/1436/03(H9N2) nucleoprotein
DQ116505.1


A/pigeon/Hong Kong/WF286/2000(H9N2) matrix protein 1 (M) and
DQ107509.1


matrix protein 2 (M)



A/quail/Hong Kong/YU415/2002(H9N2) matrix protein 1 (M) and
DQ107516.1


matrix protein 2 (M)



A/quail/Hong Kong/SSP225/2001(H9) matrix protein 1 (M) and
DQ107512.1


matrix protein 2 (M)



A/quail/Hong Kong/YU1495/2000(H9N2) matrix protein 1 (M) and
DQ107510.1


matrix protein 2 (M)



A/quail/Hong Kong/A28945/88(H9N2) hemagglutinin precursor
AY206675.1


A/shorebird/Delaware/276/99 (H9N2) nonfunctional matrix protein
AY664464.1


A/shorebird/Delaware/113/2001(H9N2) matrix protein 1 (M) and
DQ107505.1


matrix protein 2 (M)



A/silky chicken/Hong Kong/WF266/2002(H9N2) matrix protein 2 (M)
DQ107515.1


and matrix protein 1 (M)



A/shorebird/Delaware/77/2001(H9N2) matrix protein 1 (M) and
DQ107497.1


matrix protein 2 (M)



A/guinea fowl/Hong Kong/WF10/99(H9N2) hemagglutinin precursor
AY206676.1


A/swine/Hangzhou/1/2006(H9N2) nucleocapsid protein (NP)
DQ907704.1


A/swine/Hangzhou/1/2006(H9N2)) matrix protein 1 (M1)
EF055887.1


A/swine/Hangzhou/1/2006(H9N2)) nonstructural protein 1 (NS1)
DQ823385.1


A/Sw/ShanDong/1/2003(H9N2) hemagglutinin (HA)
AY294658.1


A/turkey/CA/6889/80(H9N2) matrix protein 1 (M) and matrix
DQ107491.1


protein 2 (M)



A/turkey/TX/28737/81(H9N2) matrix protein 1 (M) and matrix
DQ107493.1


protein 2 (M)



A/turkey/MN/511/78(H9N2) matrix protein 1 (M) and matrix
DQ107490.1


protein 2 (M)



A/turkey/Beit Herut/1267/03(H9N2) hemagglutinin
DQ104485.1


A/turkey/Beit HaLevi/1009/02(H9N2) hemagglutinin
DQ104473.1


A/turkey/Beit Herut/1265/03(H9N2) hemagglutinin
DQ104456.1


A/turkey/Beit_HaLevi/1562/03(H9N2) nucleoprotein
DQ116515.1


A/turkey/Beit_HaLevi/1566/04(H9N2) nucleoprotein
DQ116517.1


A/turkey/Beit_HaLevi/1562/03(H9N2) neuraminidase
DQ116083.1


A/turkey/Beit_HaLevi/1566/04(H9N2) neuraminidase
DQ116084.1


A/turkey/Beit_Herut/1267/03(H9N2) neuraminidase
DQ116070.1


A/turkey/Beit_Herut/1265/03(H9N2) neuraminidase
DQ116069.1


A/turkey/Beit HaLevi/1566/04(H9N2) hemagglutinin
DQ108917.1


A/turkey/Bezat/89/05(H9N2) hemagglutinin
DQ108922.1


A/turkey/Brosh/1276/03(H9N2) hemagglutinin
DQ104458.1


A/turkey/Brosh/1276/03(H9N2) neuraminidase
DQ116071.1


A/turkey/Emek Hefer/1272/03(H9N2) hemagglutinin
DQ104475.1


A/turkey/Ein Habsor/1804/04(H9N2) hemagglutinin
DQ108924.1


A/turkey/Ein Tzurim/1172/02(H9N2) hemagglutinin
DQ104451.1


A/turkey/Ein Tzurim/1738/04(H9N2) hemagglutinin
DQ108920.1


A/turkey/Ein_Tzurim/1738/04(H9N2) neuraminidase
DQ116085.1


A/turkey/Gyvat Haim Ehud/1544/03(H9N2)hemagglutinin
DQ108913.1


A/turkey/Givat Haim/810/01 (H9N2) hemagglutinin
DQ104466.1


A/turkey/Givat Haim/810/01 (H9N2) nucleoprotein
DQ116526.1


A/turkey/Givat Haim/868/02(H9N2) hemagglutinin
DQ104471.1


A/turkey/Givat Haim/622/02(H9N2) hemagglutinin
DQ104462.1


A/turkey/Givat_Haim/965/02(H9N2) nucleoprotein
DQ116498.1


A/turkey/Gyvat_Haim_Ehud/1544/03(H9N2) nucleoprotein
DQ116513.1


A/turkey/Gyvat_Haim_Ehud/1544/03(H9N2) neuraminidase
DQ116082.1


A/tk/Givat_Haim/810/25.12.01(H9N2) neuraminidase
DQ116063.1


A/turkey/Givat_Haim/622/02(H9N2)) neuraminidase
DQ116060.1


A/turkey/Givat_Haim/965/02(H9N2) neuraminidase
DQ116057.1


A/turkey/Hod_Ezyon/699/02(H9N2) neuraminidase
DQ116062.1


A/turkey/Mishmar Hasharon/619/02 (H9N2) hemagglutinin
DQ104461.1


A/turkey/Mishmar_Hasharon/619/02(H9N2) neuraminidase
DQ116059.1


A/turkey/Kfar_Vitkin/616/02(H9N2) neuraminidase
DQ116058.1


A/turkey/Kfar Vitkin/616/02 (H9N2) hemagglutinin
DQ104460.1


A/turkey/Kfar Vitkin/615/02 (H9N2)hemagglutinin
DQ104459.1


A/turkey/Kfar Vitkin/615/02 (H9N2) nucleoprotein
DQ116520.1


A/turkey/Kfar_Vitkin/616/02(H9N2)) nucleoprotein
DQ116521.1


A/turkey/Kfar Warburg/1224/03(H9N2) hemagglutinin
DQ104455.1


A/tk/Kfar_Vitkin/615/02(H9N)) neuraminidase
DQ116067.1


A/turkey/MishmarHasharon/619/02(H9N2) nucleoprotein
DQ116522.1


A/turkey/Naharia/1013/02(H9N2) hemagglutinin
DQ104449.1


A/turkey/Nahalal/1547/04(H9N2) hemagglutinin
DQ108932.1


A/turkey/Neve Ilan/90710/00 (H9N2) nucleoprotein
DQ116529.1


A/tk/Neve_Ilan/90710/00(H9N2) neuraminidase
DQ116066.1


A/turkey/Qevuzat_Yavne/1242/03(H9N2) neuraminidase
DQ116086.1


A/turkey/Sapir/1199/02(H9N2) hemagglutinin
DQ104452.1


A/turkey/Shadmot Dvorah/1567/04(H9N2) nucleoprotein
DQ116518.1


A/turkey/Shadmot Dvorah/1567/04(H9N2) hemagglutinin
DQ108918.1


A/turkey/Tzur Moshe/1565/04(H9N2) nucleoprotein
DQ116516.1


A/turkey/Tzur Moshe/1565/04(H9N2) hemagglutinin
DQ108916.1


A/turkey/Yedidia/625/02 (H9N2) hemagglutinin
DQ104463.1


A/turkey/Yedidia/625/02 (H9N2) nucleoprotein
DQ116523.1


A/turkey/Yedidia/625/02 (H9N2) neuraminidase
DQ116061.1


A/turkey/Yedidia/911/02(H9N2) hemagglutinin
DQ104448.1


A/turkey/Avigdor/1215/03(H9N2) hemagglutinin
DQ104454.1


A/turkey/Avigdor/1209/03(H9N2) hemagglutinin
DQ104453.1


A/turkey/Avichail/1075/02(H9N2) hemagglutinin
DQ104450.1


A/turkey/Avigdor/1920/04(H9N2) hemagglutinin
DQ108926.1


A/pintail/Alberta/49/2003(H9N5) matrix protein 1 (M) and matrix
DQ107498.1


protein 2 (M)



A/red knot/Delaware/2552/87 (H9N5) nonfunctional matrix protein
AY664472.1


A/duck/Hong Kong/147/77(H9N6) hemagglutinin precursor
AY206671.1


A/shorebird/Delaware/270/2001(H9N7) matrix protein 1 (M) and
DQ107504.1


matrix protein 2 (M)



A/shorebird/Delaware/277/2000(H9N7) matrix protein 1 (M) and
DQ107507.1


matrix protein 2 (M)



A/shorebird/Delaware/275/2001(H9N7)) matrix protein 2 (M) and
DQ107506.1


matrix protein 1 (M)



A/ruddy turnstone/Delaware/116/98 (H9N8) nonfunctional matrix
AY664435.1


protein



A/shorebird/Delaware/141/2002(H9N9) matrix protein 1 (M) and
DQ107503.1


matrix protein 2 (M)



A/ruddy turnstone/Delaware/103/2002(H9N9) matrix protein 1 (M)
DQ107502.1


and matrix protein 2 (M)



A/shorebird/Delaware/29/2002(H9N9) matrix protein 1 (M) and
DQ107501.1


matrix protein 2 (M)



A/shorebird/Delaware/18/2002(H9N9) matrix protein 1 (M) and
DQ107500.1


matrix protein 2 (M)



A/ruddy turnstone/Delaware/259/98 (H9N9) nonfunctional matrix
AY664469.1


protein



A/duck/Eastern China/527/2003(H10N3) segment 6 neuraminidase
EU429716.1


(NA)



A/duck/Eastern China/495/2003(H10N3) segment 6 neuraminidase
EU429715.1


(NA)



A/duck/Eastern China/372/2003(H10N3) segment 6 neuraminidase
EU429714.1


(NA)



A/duck/Eastern China/488/2003(H10N3) segment 6 neuraminidase
EU429712.1


(NA)



A/duck/Eastern China/453/2002(H10N3) segment 6 neuraminidase
EU429711.1


(NA)



A/duck/Eastern China/412/2003(H10N3) segment 6 neuraminidase
EU429710.1


(NA)



A/duck/Eastern China/404/2003(H10N3) segment 6 neuraminidase
EU429709.1


(NA)



A/duck/Eastern China/397/2003(H10N3) segment 6 neuraminidase
EU429708.1


(NA)



A/duck/Eastern China/502/2003(H10N3) segment 6 neuraminidase
EU429705.1


(NA)



A/duck/Eastern China/395/2003(H10N3) segment 6 neuraminidase
EU429704.1


(NA)



A/duck/Eastern China/356/2003(H10N3) segment 6 neuraminidase
EU429703.1


(NA)



A/duck/Eastern China/368/2003(H10N3) segment 6 neuraminidase
EU429702.1


(NA)



A/chicken/Singapore/1993(H10N5) M2 protein
EU014145.1


A/red knot/Delaware/2561/87 (H10N5) nonfunctional matrix
AY664441.1


protein



A/chicken/Germany/N/1949(H10N7) segment 6 neuraminidase (NA)
EU429796.1


A/ruddy turnstone/Delaware/2764/87 (H10N7) nonfunctional matrix
AY664462.1


protein



A/mallard/Alberta/71/98 (H10N7) nonfunctional matrix protein
AY664485.1


A/mallard/Alberta/90/97 (H10N7) nonfunctional matrix protein
AY664446.1


A/mallard/Alberta/110/99(Hl0N7) nonfunctional matrix protein
AY664481.1


A/mallard/Alberta/297/77 (H10N7) nonfunctional matrix protein
AY664430.1


A/mallard/Alberta/223/98 (H10N8) nonfunctional matrix protein
AY664486.1


A/ruddy turnstone/New Jersey/51/85 (H11N1) nonfunctional matrix
AY664479.1


protein



A/duck/Nanchang/1749/1992(H11N2) nucleoprotein (NP)
U49094.1


A/duck/Hong Kong/62/1976(H11N2) polymerase (PB1)
U48280.1


A/duck/Yangzhou/906/2002(H11N2) hemagglutinin
DQ080993.1


A/shorebird/Delaware/86/99 (H11N2) nonfunctional matrix protein
AY664463.1


A/ruddy turnstone/Delaware Bay/2762/1987(H11N2)polymerase PB2
CY126279.1


(PB2)



A/ruddy turnstone/Delaware/2762/87 (H11N2) nonfunctional
AY664459.1


matrix protein



A/ruddy turnstone/Delaware Bay/2762/1987(H11N2) polymerase PB1
CY126278.1


(PB1) and PB1-F2 protein (PB1-F2)



A/ruddy turnstone/Delaware/2589/87 (H11N4) nonfunctional matrix
AY664478.1


protein



A/duck/England/1/1956(H11N6) segment 6 neuraminidase (NA)
EU429795.1


A/mallard/Alberta/125/99 (H11N6) nonfunctional matrix protein
AY664483.1


A/duck/Memphis/546/1974(H11N9) segment 6 neuraminidase (NA)
EU429798.1


A/mallard/Alberta/122/99 (H11N9) nonfunctional matrix protein
AY664444.1


A/Mallard Duck/Alberta/342/83(H12N1) segment 4 hemagglutinin
AF310991.1


(HA1)



A/ruddy turnstone/Delaware/67/98(H12N4) nonfunctional matrix
AY664470.1


protein



A/Ruddy Turnstone/Delaware/67/98(H12N4) segment 4 hemagglutinin
AF310990.1


(HA1)



A/mallard/Alberta/52/97 (H12N5) nonfunctional matrix protein
AY664448.1


A/mallard/Alberta/223/77 (H12N5) nonfunctional matrix protein
AY664431.1


A/Laughing Gull/New Jersey/171/92(H12N5) segment 4
AF310992.1


hemagglutinin (HA1)



A/ruddy turnstone/Delaware/265/98 (H12N8) nonfunctional matrix
AY664438.1


protein



A/herring gull/New Jersey/782/86 (H13N2) nonfunctional matrix
AY664475.1


protein



A/shorebird/Delaware/224/97 (H13N6) nonfunctional matrix
AY664421.1


protein



A/PR/8/34 (H1N1) x A/England/939/69 (H3N2) PB1 protein
AJ564806.1


A/PR/8/34 (H1N1) x A/England/939/69 (H3N2)PB2 protein
AJ564804.1


A/duck/Czechslovakia/56(H4N6) x A/USSR/90/77(H1N1))
EU643639.1


neuraminidase (NA)



A/duck/Czechslovakia/56(H4N6) x A/USSR/90/77(H1N1))
EU643638.1


neuraminidase (NA)



A/duck/Ukraine/63(H3N8) x A/USSR/90/77(H1N1)) neuraminidase
EU643637.1


(NA)



A/duck/Ukraine/63(H3N8) x A/USSR/90/77(H1N1)) neuraminidase
EU643636.1


(NA)



RCB1-XXI: A/USSR/90/77(H1N1) x A/Duck/Czechoslov 56 (H4N6)
AF290438.1


segment 4 hemagglutinin



RCB1: A/USSR/90/77(H1N1) x A/Duck/Czechoslov 56 (H4N6)
AF290437.1


hemagglutinin



PX14-XIII (A/USSR/90/77(H1N1) x A/Pintail
AF290442.1


Duck/Primorie/695/76(H2N3)) segment 4 hemagglutinin



PX14(A/USSR/90/77(H1N1) xA/Pintail Duck/Primorie/695/76(H2N3))
AF290441.1


segment 4 hemagglutinin



PX8-XIII(A/USSR/90/77(H1N1) xA/Pintail



Duck/Primorie/695/76(H2N3)) segment 4 hemagglutinin



PX8(A/USSR/90/77(H1N1) xA/Pintail Duck/Primorie/695/76(H2N3))
AF290439.1


segment 4 hemagglutinin



A/swine/Schleswig-Holstein/1/93 hemagglutinin (HA)
U72669.1


A/swine/England/283902/93 hemagglutinin (HA)
U72668.1


A/swine/England/195852/92 hemagglutinin (HA)
U72667.1


A/swine/England/117316/86 hemagglutinin (HA)
U72666.1


A/turkey/Germany/2482/90) hemagglutinin (HA)
U96766.1
















TABLE 12







Influenza B Antigens









GenBank


Strain/Protein
Access No.





B/Daeku/47/97 hemagglutinin
AF521237.1


B/Daeku/45/97 hemagglutinin
AF521236.1


B/Daeku/10/97 hemagglutinin
AF521221.1


B/Daeku/9/97 hemagglutinin
AF521220.1


B/Gyeonggi/592/2005 neuraminidase
DQ231543.1


B/Gyeonggi/592/2005 hemagglutinin
DQ231538.1


B/Hong Kong/5/72 neuraminidase
AF305220.1


B/Hong Kong/5/72 hemagglutinin
AF305219.1


B/Hong Kong/157/99 hemagglutinin
AF387503.1


B/Hong Kong/157/99 hemagglutinin
AF387502.1


B/Hong Kong/156/99 hemagglutinin
AF387501.1


B/Hong Kong/156/99 hemagglutinin
AF387500.1


B/Hong Kong/147/99 hemagglutinin
AF387499.1


B/Hong Kong/147/99 hemagglutinin
AF387498.1


B/Hong Kong/110/99 hemagglutinin
AF387497.1


B/Hong Kong/110/99 hemagglutinin
AF387496.1


B/Incheon/297/2005 hemagglutinin
DQ231539.1


B/Incheon/297/2005 neuraminidase
DQ231542.1


B/Lee/40 polymerase protein (PB1)
D00004.1


B/Michigan/22572/99 hemagglutinin
AY129961.1


B/Michigan/22723/99 hemagglutinin (HA)
AY112992.1


B/Michigan/22631/99 hemagglutinin (HA)
AY112991.1


B/Michigan/22587/99 hemagglutinin (HA)
AY112990.1


B/New York/20139/99 hemagglutinin
AY129960.1


B/Panama/45/90 nucleoprotein
AF005739.1


B/Panama/45/90 polymerase (PA)
AF005738.1


B/Panama/45/90 polymerase (PB2)
AF005737.1


B/Panama/45/90 polymerase (PB1)
AF005736.1


B/Pusan/250/99 hemagglutinin
AF521218.1


B/Pusan/255/99 hemagglutinin
AF521226.1


B/Pusan/270/99 hemagglutinin
AF521219.1


B/Pusan/285/99 hemagglutinin
AF521217.1


B/Riyadh/01/2007 segment 8 nuclear export protein (NEP)
GU135839.1


and non structural protein 1 (NS1)



B/Seoul/6/88 hemagglutinin
AF521238.1


B/Seoul/12/88 hemagglutinin
AF521239.1


B/Seoul/1/89 hemagglutinin
AF521230.1


B/Seoul/37/91 hemagglutinin
AF521229.1


B/Seoul/38/91 hemagglutinin
AF521227.1


B/Seoul/40/91 hemagglutinin
AF521235.1


B/Seoul/41/91 hemagglutinin
AF521228.1


B/Seoul/13/95 hemagglutinin
AF521225.1


B/Seoul/12/95 hemagglutinin
AF521223.1


B/Seoul/17/95 hemagglutinin
AF521222.1


B/Seoul/21/95 hemagglutinin
AF521224.1


B/Seoul/16/97 hemagglutinin
AF521233.1


B/Seoul/19/97 hemagglutinin
AF521231.1


B/Seoul/28/97 hemagglutinin
AF521234.1


B/Seoul/31/97 hemagglutinin
AF521232.1


B/Seoul/232/2004 neuraminidase
DQ231541.1


B/Seoul/1163/2004 neuraminidase
DQ231540.1


B/Seoul/1163/2004 hemagglutinin
DQ231537.1


B/Sichuan/379/99 hemagglutinin (HA)
AF319590.1


B/Sichuan/38/2000 hemagglutinin (HA)
AF319589.1


B/South Carolina/25723/99 hemagglutinin
AY129962.1


B/Switzerland/4291/97 hemagglutinin
AF387505.1


B/Switzerland/4291/97 hemagglutinin
AF387504.1


B/Taiwan/21706/97 nonstructural protein 1 (NS1)
AF492479.1


B/Taiwan/21706/97 hemagglutinin (HA)
AF026162.1


B/Taiwan/3143/97 nonstructural protein 1 (NS1)
AF492478.1


B/Taiwan/3143/97 haemagglutinin (HA)
AF026161.1


B/Taiwan/2026/99 nonstructural protein 1 (NS1)
AF492481.1


B/Taiwan/2026/99 hemagglutinin
AY604741.1


B/Taiwan/2027/99 nonstructural protein 1 (NS1)
AF492480.1


B/Taiwan/2027/99 hemagglutinin
AY604742.1


B/Taiwan/1243/99 nonstructural protein NS1(NS1)
AF380504.1


B/Taiwan/1243/99 hemagglutinin
AY604740.1


B/Taiwan/2195/99 hemagglutinin
AY604743.1


B/Taiwan/2195/99 nonstructural protein 1 (NS1)
AF492482.1


B/Taiwan/1293/2000 nonstructural protein NS1(NS1)
AF380509.1


B/Taiwan/1293/00 hemagglutinin
AY604746.1


B/Taiwan/1293/2000 hemagglutinin (HA)
AF492477.1


B/Taiwan/1265/2000 nonstructural protein NS1 (NS1)
AF380508.1


B/Taiwan/1265/00 hemagglutinin
AY604745.1


B/Taiwan/4184/2000 nonstructural protein NS1 (NS1)
AF380507.1


B/Taiwan/4184/00 hemagglutinin (HA)
AY604750.1


B/Taiwan/31511/2000 nonstructural protein NS1 (NS1)
AF380505.1


B/Taiwan/31511/00 hemagglutinin (HA)
AY604748.1


B/Taiwan/12192/2000 hemagglutinin
AY604747.1


B/Taiwan/41010/00 hemagglutinin (HA)
AY604749.1


B/Taiwan/41010/2000 nonstructural protein NS1 (NS1)
AF380506.1


B/Taiwan/0409/00 hemagglutinin (HA)
AY604744.1


B/Taiwan/202/2001 nonstructural protein 1 (NS1)
AF380512.1


B/Taiwan/202/2001 hemagglutinin (HA)
AF366076.1


B/Taiwan/11515/2001 nonstructural protein 1 (NS1)
AF380511.1


B/Taiwan/11515/01 hemagglutinin
AY604754.1


B/Taiwan/11515/2001 hemagglutinin (HA)
AF366075.1


B/Taiwan/1103/2001 nonstructural protein NS1 (NS1)
AF380510.1


B/Taiwan/1103/01 hemagglutinin
AY604755.1


B/Taiwan/114/2001 hemagglutinin (HA), HA-4 allele
AF492476.1


B/Taiwan/2805/2001 hemagglutinin (HA)
AF400581.1


B/Taiwan/2805/01 hemagglutinin (HA)
AY604752.1


B/Taiwan/0114/01 hemagglutinin (HA)
AY604753.1


B/Taiwan/0202/01 hemagglutinin (HA)
AY604751.1


B/Taiwan/4119/02 hemagglutinin (HA)
AY604778.1


B/Taiwan/4602/02 hemagglutinin (HA)
AY604777.1


B/Taiwan/1950/02 hemagglutinin (HA)
AY604776.1


B/Taiwan/1949/02 hemagglutinin (HA)
AY604775.1


B/Taiwan/1584/02 hemagglutinin (HA)
AY604774.1


B/Taiwan/1561/02 hemagglutinin (HA)
AY604773.1


B/Taiwan/1536/02 hemagglutinin (HA)
AY604772.1


B/Taiwan/1534/02 hemagglutinin (HA)
AY604771.1


B/Taiwan/1503/02 hemagglutinin (HA)
AY604770.1


B/Taiwan/1502/02 hemagglutinin (HA)
AY604769.1


B/Taiwan/1013/02 hemagglutinin (HA)
AY604768.1


B/Taiwan/0993/02 hemagglutinin (HA)
AY604766.1


B/Taiwan/0932/02 hemagglutinin (HA)
AY604765.1


B/Taiwan/0927/02 hemagglutinin (HA)
AY604764.1


B/Taiwan/0880/02 hemagglutinin (HA)
AY604763.1


B/Taiwan/0874/02 hemagglutinin (HA)
AY604762.1


B/Taiwan/0730/02 hemagglutinin (HA)
AY604761.1


B/Taiwan/0722/02 hemagglutinin (HA)
AY604760.1


B/Taiwan/0702/02 hemagglutinin (HA)
AY604759.1


B/Taiwan/0654/02 hemagglutinin (HA)
AY604758.1


B/Taiwan/0600/02 hemagglutinin (HA)
AY604757.1


B/Taiwan/0409/02 hemagglutinin (HA)
AY604756.1


B/Taiwan/0879/02 nonfunctional hemagglutinin
AY604767.1


B/Taiwan/3532/03 hemagglutinin (HA)
AY604794.1


B/Taiwan/2551/03 hemagglutinin (HA)
AY604793.1


B/Taiwan/1618/03 hemagglutinin (HA)
AY604792.1


B/Taiwan/1574/03 hemagglutinin (HA)
AY604791.1


B/Taiwan/1013/03 hemagglutinin (HA)
AY604790.1


B/Taiwan/0833/03 hemagglutinin (HA)
AY604789.1


B/Taiwan/0735/03 hemagglutinin (HA)
AY604788.1


B/Taiwan/0699/03 hemagglutinin (HA)
AY604787.1


B/Taiwan/0684/03 hemagglutinin (HA)
AY604786.1


B/Taiwan/0616/03 hemagglutinin (HA)
AY604785.1


B/Taiwan/0615/03 hemagglutinin (HA)
AY604784.1


B/Taiwan/0610/03 hemagglutinin (HA)
AY604783.1


B/Taiwan/0576/03 hemagglutinin (HA)
AY604782.1


B/Taiwan/0569/03 hemagglutinin (HA)
AY604781.1


B/Taiwan/0562/03 hemagglutinin (HA)
AY604780.1


B/Taiwan/0002/03 hemagglutinin (HA)
AY604779.1


B/Taiwan/773/2004 hemagglutinin (HA)
EU068195.1


B/Taiwan/187/2004 hemagglutinin (HA)
EU068194.1


B/Taiwan/3892/2004 hemagglutinin (HA)
EU068193.1


B/Taiwan/562/2004 hemagglutinin (HA)
EU068191.1


B/Taiwan/234/2004 hemagglutinin (HA)
EU068188.1


B/Taiwan/4897/2004 hemagglutinin (HA)
EU068186.1


B/Taiwan/8579/2004 hemagglutinin (HA)
EU068184.1


B/Taiwan/184/2004 hemagglutinin (HA)
EU068183.1


B/Taiwan/647/2005 hemagglutinin (HA)
EU068196.1


B/Taiwan/877/2005 hemagglutinin (HA)
EU068198.1


B/Taiwan/521/2005 hemagglutinin (HA)
EU068189.1


B/Taiwan/1064/2005 hemagglutinin (HA)
EU068192.1


B/Taiwan/3722/2005 hemagglutinin (HA)
EU068197.1


B/Taiwan/5049/2005 hemagglutinin (HA)
EU068190.1


B/Taiwan/5011/2005 hemagglutinin (HA)
EU068187.1


B/Taiwan/4659/2005 hemagglutinin (HA)
EU068185.1


B/Taiwan/25/2005 hemagglutinin (HA)
EU068182.1


B/Taiwan/1037/2005 hemagglutinin (HA)
EU068181.1


B/Taiwan/62/2005 hemagglutinin (HA)
EU068180.1


B/Taiwan/591/2005 hemagglutinin (HA)
EU068179.1


B/Taiwan/649/2005 hemagglutinin (HA)
EU068178.1


B/Taiwan/4554/2005 hemagglutinin (HA)
EU068177.1


B/Taiwan/987/2005 hemagglutinin (HA)
EU068176.1


B/Taiwan/2607/2006 hemagglutinin (HA)
EU068175.1


B/Vienna/1/99 hemagglutinin
AF387495.1


B/Vienna/1/99 hemagglutinin
AF387494.1


B/Vienna/1/99 hemagglutinin
AF387493.1


B/Vienna/1/99 hemagglutinin
AF387492.1
















TABLE 13







Influenza C Antigens









GenBank


Strain/Protein
Access No.





C/JHB/1/66) hemagglutinin-esterase-fusion
AY880247.1


protein (HEF) mRNA, complete cds.



STRAIN C/ANN ARBOR/1/50) persistent variant
AF102027.1


segment 7 non-structural protein 1 (NS1) mRNA,



complete cds



(STRAIN C/ANN ARBOR/1/50) wild type segment 7
AF102026.1


non-structural protein 1 (NS1) mRNA, complete cds



(C/JHB/1/66) hemagglutinin-esterase-fusion protein
AY880247.1


(HEF) mRNA, complete cds



(STRAIN C/BERLIN/1/85) mRNA for basic polymerase
X55992.1


2 precursor
















TABLE 14







H7 Hemagglutinin Amino Acid Sequences









Accession No/

SEQ


Strain/Protein
Amino Acid Sequence
ID NO:












AAM19228
ACVLVEAKGDKICLGHHAVVNGTKVNTLTEKGIEVVNATETVETA
1


A/turkey/
NIGKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEFESDLIIERR



Minnesota/
EGNDVCYPGKFTNEESLRQILRGSGGIDKESMGFTYSGIITNGAT



38429/1988
SACRRSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPALIVW



1988// HA
GIHHSGSTTEQTKLYGSGNKLITVESSKYQQSFTPSPGARPQVNG



20335017
ESGRIDFHWMLLDPNDTVTFTFNGAFIAPDRASFFKGESLGVQSD




VPLDSSCGGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQPSLL




LATGMRNVPENPKTRGLFGAIAGFIEKDGGSHYG






AAY46211
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
2


A/mallard/
NATETVERTNVPRICSRGKRTVDLGQCGLLGTITGPPQCDQFLEF



Sweden/91/2002
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY



2002// HA
SGIRTNGAPSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



66394828
RNDPALIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSFVPS




PGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQIDANCEGDCYHSGGTIISNLPFQNINSRAVGKCP




RYVKQESLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




AMGLVFMCVKNGNMRCTICI






ABI84694
MNTQILVFIACVLVEAKGDKICLGHHAVVNGTKVNTLTEKGIEVV
3


A/turkey/
NATETVETANIGKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF



Minnesota/
ESDLIIERREGNDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY



1/1988
SGIRTNGATSACRRSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNP



1988/07/13 HA
RNKPALIVWGIHHSGSTTEQTKLYGSGNKLITVGSSKYQQSFTPS



115278573
PGARPQVNGQSGRIDFHWMLLDPNDTVTFTFNGAFIAPDRASFFK




GESLGVQSDVPLDSSCGGDCFHSGGTIVSSLPFQNINPRTVGKCP




RYVKQPSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW




YGFKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI




DNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT




YDHAQYRAESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI




AMGLVFICIKNGNMRCTICI






ABS89409
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVV
4


A/blue-winged
NATETVETANIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF



teal/Ohio/566/
DTDLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY



2006 2006// HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNP



155016324
RNKPALIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFTPS




PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR




GESLGVQSDVPLDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCP




RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI




DNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT




YDHTQYRTESLQNRIQIDPVRLSSGYKDIILWFSFGASCFLLLAI




AMGLVFICIKNGNMRCTICI






ACD03594
MNTQILAFIACMLVGVRGDKICLGHHAVANGTKVNTLTEKGIEVV
5


A/ruddy
NATETVESANIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF



turnstone/DE/
DSDLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY



1538/2000
SGIRTNGATSACRRLGSSFYAEMKWLLSNSDNAAFPQMTKSYRNP



2000// HA
RNKPALIIWGVHHSGSANEQTKLYGSGNKLITVGSSKYQQSFTPS



187384848
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR




GESLGIQSDVPLDSSCGGDCFHSGGTIVSSLPFQNINPRTVGKCP




RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELM




DNEFNEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT




YDHTQYRTESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI




AMGLIFICIKNGNMRCTICI






BAH22785
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
6


A/duck/Mongolia/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



119/2008
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIGKETMGFTY



2008// HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



223717820
RKDPALIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSFVPS




PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHNGGTIISNLPFQNINSRTVGKCP




RYVKQESLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIERTNQQFELI




DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSNGYKDVILWFSFGASCFILLAI




AMGLVFICVKNGNMRCTICI






CAY39406
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
7


A/Anascrecca/
NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Spain/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY



1460/2008
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2008/01/26 HA
RKDPALIIWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS



254674376
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNINSRAVGKCP




RYVKQESLMLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFTEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




AMGLVFICVKNGNMRCTICI






ACX53683
MNIQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
8


A/goose/Czech
NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Republic/1848-
SADLIIERRGGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY



K9/2009
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2009/02/04 HA
RKDPALIIWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS



260907763
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLK




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNINSRAVGKCP




RYVKQESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQINPVKLSSGYKDVILWFSFGASCFILLAI




AMGLVFICVKNGNMRCTICI






ACZ48625
MNTQILVFIACVLVEAKGDKICLGHHAVVNGTKVNTLTEKGIEVV
9


A/turkey/
NATETVETANIGKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF



Minnesota/
ESDLIIERREGNDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY



38429/1988
SGIRTNGATSACRRSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNP



1988// HA
RNKPALIVWGIHHSGSTTEQTKLYGSGNKLITVGSSKYQQSFTPS



269826341
PGARPQVNGQSGRIDFHWMLLDPNDTVTFTFNGAFIAPDRASFFK




GESLGVQSDVPLDSSCGGDCFHSGGTIVSSLPFQNINPRTVGKCP




RYVKQPSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW




YGFKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFEL






ADC29485
STQSAIDQITGKLNRLIEKTNQQFELIDNEFTEVEKQIGNVINWT
10


A/mallard/Spain/
RDSMTEVWSYNAELLVAMENQHTIDLADSEMNKLYERVKRQLREN



08.00991.3/
AEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKYREEAMQNRIQID



2005 2005/11/
PVKLSSGYKDVILWFSFGASCFILL



HA 284927336







ADK71137
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVV
11


A/blue-winged
NATETVETANIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF



teal/Guatemala/
DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY



CIP049-
SGIRTNGATSACRRSGSSSYAEMKWLLSNSDNAAFPQMTKSYRNP



01/2008
RNKPALIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFTPS



2008/02/07 HA
PGTRPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFLR



301333785
GKSLGIQSDVPLDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCP




RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQHFELI




DNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT




YDHTQYRTESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI




AMGLVFICIKNGNMRCTICI






ADK71148
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVV
12


A/blue-winged
NXTETVETANIKKICTHGKRPTDLGQCGLLGTLIGPPQCDRFLEF



teal/Guatemala/
DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY



CIP049-
SGIRTNGATSACRRSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNP



02/2008
RNKPALIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFTPS



2008/03/05 HA
PGTRPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFLR



301333804
GKSLGIQSDVPLDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCP




RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI




DNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT




YDHTQYRTESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI




AMGLVFICIKNGNMRCTICI






ADN34727
MNIQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
13


A/goose/Czech
NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Republic/1848-
SADLIIERRGGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY



T14/2009
SGIRTNGXTSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2009/02/04 HA
RKDPALIIWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS



307141869
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLK




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNINSRAVGKCP




RYVKQESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQINPVKLSSGYKDVILWFSFGASCFILLAI




AMGLVFICVKNGNMRCTICI






AEK84760
PAFIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSGGTIISNLP
14


A/wild
FQNINSRAVGKCPRYVKQESLMLATGMKNVPELPKGRGLFGAIAG



bird/Korea/A14/
FIENGWEGLIDGWYGFRHQNAQGEGTAADYKSTQSAIDQITGKLN



2011 2011/02/
RLIEKTNQQFELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAEL



HA 341610308
LVAMENQHTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFHK




CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILW




FSFGASCFILLAIAMGLVFICVKNGNMRCTICI






AEK84761
ILVFALVAIIPTNANKIGLGHHAVSNGTKVNTLTERGVEVFNATE
15


A/wild
TVERTNVPRICSKGKKTVDLGQCGLRGTITGPPQCDQFLKFSPDL



bird/Korea/A3/
IIERQKGSDVCYPGKFVNEKPLRQILRESGGIDKETMGFAYNGIK



2011 2011/02/
TNGPPIACRKSGSSFYAKMKWLLSNTDKAAFPQMTKSYKNTRRNP



HA 341610310
ALIVWGIHHSGSTTKQTKLYGIGSNLITVGSSNYQQSFVPSPGAR




PQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIPPDRASFLRGKSM




GIQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVK




QESLMLATGMKNVPELPKGKGLFGAIAGFIENGWEGLIDGWYGFR




HQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEF




TEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLADSEM




NKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHS




KYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIAMGL




VFICVKNGNMRCTICI






AEK84763
ILVFALVAIIPTNANKIGLGHHAVSNGTKVNTLTERGVEFFNATE
16


A/wild
TVEPTNVPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEFSADL



bird/Korea/A9/
IIERREGSDVCYPGKFVNEKALRQILRESGGIDKETMGFAYSGIK



2011 2011/02/
TNGPPIACRKSGSSFYAKMKWLLSNTDKAAFPQMTKSYKNTRRDP



HA 341610314
ALIVWGIHHSGSTIKQINLYGIGSNLITVGSSNYQQSFVPSPGAR




PQVNGQSGRIDFHWLILNPNDTVIFIENGAFIAPDRASFLIGKSM




GIQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVK




QESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYGFR




HQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEF




TEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLADSEM




NKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHS




KYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIAMGL




VFICVKNGNMRCTICI






AEK84765
LVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVNATET
17


A/spot-billed
VERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEFSADLI



duck/Korea/447/
IERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTYSGIRT



2011 2011/04/
NGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRDPA



HA 341610318
LIVWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPSPGARP




QVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLRGKSMG




IQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQ




ESLMLATGMKNVPEPPKGRGLFGAIAGFIENGWEGLIDGWYGFRH




QNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFT




EVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLADSEMN




KLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMARIRNNTYDHSK




YREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIAMGLV




FICVKNGNMRCTICI






AEM98291
SILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVNAT
18


A/wild
ETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEFSAD



duck/Mongolia/
LIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTYSGI



1-241/2008
RTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKD



2008/04/
PALIIWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPSPGA



HA 344196120
RPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLRGKS




MGIQSGVQVDANCEGDCYHSGGSIISNLPFQNINSRAVGKCPRYV




KQESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYGF




RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNE




FTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLADSE




MNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDH




SKYREEAMQNRIQINPVKLSSGYKDVILWFSFGASCFILLAIAMG




LVFICVKNGNMRCTI






AFM09439
QILAFIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVVNAT
19


A/emperor
ETVETVNIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEFDAD



goose/Alaska/
LIIERRKGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTYSGI



44063-061/2006
RTNGATSACRRSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNK



2006/05/23 HA
PALIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFVPSPGA



390535062
RPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPERASFFRGES




LGVQSDVPLDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCPRYV




KQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGF




RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDNE




FSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLADSE




MNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNTYDH




TQYRTESLQNRIQINPVKLSSGYKDIILWFSFGASCFLLLAIAMG




LVFICIKNGNMRCTICI






AFV33945
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTERRIEVV
20


A/guinea
NATETVETANIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF



fowl/Nebraska/
DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY



17096-1/2011
SGIRTNGATSACRRSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNP



2011/04/05 HA
RNKPALIVWGVHHSGSATEQTKLYGSGSKLITVGSSKYQQSFTPS



409676820
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR




GESLGVQSDVPLDSGCEGDCFHKGGTIVSSLPFQNINPRTVGKCP




RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI




DNEFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT




YDHTQYRAESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI




AMGLVFICIKNGNMRCTICI






AFV33947
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVV
21


A/goose/
NATETVETANIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF



Nebraska/17097-
DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY



4/2011
SGIRTNGATSACRRSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNP



2011/04/05 HA
RNKPALIVWGVHHSASATEQTKLYGSGSKLITVGSSKYQQSFTPS



409676827
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR




GESLGVQSDVPLDSGCEGDCFHKGGTIVSSLPFQNINPRTVGKCP




RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI




DNEFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT




YDHTQYRAESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI




AMGLVFICIKNGNMRCTICI






AFX85260
MNTQILAFIACMLIGINGDKICLGHHAVANGTKVNTLTERGIEVV
22


A/ruddy
NATETVETANIKRICTQGKRPIDLGQCGLLGTLIGPPQCDQFLEF



turnstone/
DSDLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY



Delaware
SGIRTNGATSACIRLGSSFYAEMKWLLSNSDNAAFPQMTKSYRNP



Bay/220/1995
RNKPALIIWGVHHSGSANEQTKLYGSGNKLITVGSSKYQQSFTPS



1995/05/21 HA
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR



423514912
GESLGVQSDVPLDSSCGGDCFHSGGTIVSSLPFQNINPRTVGRCP




RYVKQTSLLLATGMKNVPENPKTRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI




DNEFNEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT




YDHTQYRTESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI




AMGLVFICIKNGNMRCTICI






AGE08098
MNTQILTLIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVV
23


A/northern
NATETVETANIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF



shoverl/
DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY



Mississippi/
SGIRTNGATSACRRSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNP



11OS145/2011
RNKPALIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFTPS



2011/01/08 HA
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR



444344488
GESLGVQSDVPLDSGCEGDCFHNGGTIVSSLPFQNINPRTVGKCP




RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI




DNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT




YDHTQYRAESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI




AMGLVFICIKNGNMRCTICI






AGI60301
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
24


A/Hangzhou/1/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



2013 2013/03/24
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



HA 475662454
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT




RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGISGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGI60292
MNTQILVFALIAIIPANADKICLGHHAVSNGTKVNTLTERGVEVV
25


A/Shanghai/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



4664T/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/03/05 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



476403560
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCHHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGJ72861
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGGEVV
26


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQGGPRGTITGPPQCDQFLEF



Zhejiang/DTID-
SADLIMERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



ZJU01/2013
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2013/04/
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



HA 479280294
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGJ73503
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
27


A/Nanjing/1/
NATETVERTNIPRICSKGKMTVDLGQCGLLGTITGPPQCDQFLEF



2013 2013/03/28
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



HA 479285761
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT




RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






BAN16711
MNTQVLVFALMAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
28


A/duck/Gunma/
NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



466/2011 2011//
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY



HA 482661571
SGIRTNGTTSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT




RRDPALIAWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS




PGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCP




RYVKQESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRRQLRENAEEDDTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




AMGLVFICVKNGNMRCTICI






AGK84857
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
29


A/Hangzhou/2/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



2013 2013/04/01
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



HA 485649824
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQIIKSYKNT




RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGL44438
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
30


A/Shanghai/02/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/03/05 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



496493389
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGL33692
GMIDGWYGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTN
31


A/Shanghai/
QQFELIDNEFTEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ



4655T/2013
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMA



2013/02/26 HA
SIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASC



491874175
FILLAIAMGLVFICVKNGNMRCTICI






AGL33693
GMIDGWYGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTN
32


A/Shanghai/
QQFELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ



4659T/2013
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMA



2013/02/27 HA
SIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASC



491874186
FILLAIVMGLVFICVKNGNMRCTICI






AGL95088
VFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVNATETV
33


A/Taiwan/
ERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEFSADLII



S02076/2013
ERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTYSGIRTN



2013/04/22 HA
GATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPAL



501485301
IVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPGARPQ




VNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGI




QSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQR




SLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQ




NAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFNE




VEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADSEMDK




LYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKY




REEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIVMGLVF




ICVKNGNMR






AGL95098
LVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVNATET
34


A/Taiwan/
VERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEFSADLI



T02081/2013
IERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTYSGIRT



2013/04/22 HA
NGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA



501485319
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPGARP




QVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMG




IQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQ




RSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRH




QNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFN




EVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADSEMD




KLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSK




YREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIVMGLV




FICVKNGNMRCT






AGM53883
GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELID
35


A/Shanghai/
NEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLAD



5083T/2013
SEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTY



2013/04/20 HA
DHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIV



507593986
MGLVFICVKNGNMRCT






AGM53884
AQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFNEV
36


A/Shanghai/
EKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADSEMDKL



5180T/2013
YERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKYR



2013/04/23 HA
EEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIVMGLVFI



507593988
CVKNGNMRCTICI






AGM53885
QNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFN
37


A/Shanghai/
EVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADSEMD



5240T/2013
KLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSK



2013/04/25 HA
YREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIVMGLV



507593990
FICVKNGNMRCT






AGM53886
NAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFNE
38


A/Shanghai/
VEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADSEMDK



4842T/2013
LYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKY



2013/04/13 HA
REEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIVMGLVF



507593992
ICVKNGNMRCT






AGM53887
NAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFNE
39


A/Shanghai/
VEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADSEMDK



4701T/2013
LYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKY



2013/04/06 HA
REEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIVMGLVF



507593994
ICVKNGNMRCTIC






AGN69462
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
40


A/Wuxi/2/2013
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



2013/03/31 HA
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



511105778
SGIRTNGSTSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT




RKSPALIVWGIHHSVSTAEQTKLYGSGSKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGN69474
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
41


A/Wuxi/1/2013
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



2013/03/31 HA
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



511105798
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT




RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLINGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGO51387
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
42


A/Jiangsu/2/
NATETVERTNIPRICSKGKMTVDLGQCGLLGTITGPPQCDQFLEF



2013 2013/04/20
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



HA 514390990
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT




RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYRKEAMKBXIQIDPVKLSSGYKDVXJWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






BAN59726
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
43


A/duck/Mongolia/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



147/2008
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIGKETMGFTY



2008/08/29 HA
SGIRTNGATSACRRSRSSFYAEMKWLLSNTDNAAFPQMIRSYKNT



519661951
RKDPALIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSFVPS




PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHNGGTIISNLPFQNINSRTVGKCP




RYVKQESLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIERTNQQFELI




DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSNGYKDVILWFSFGASCFILLAI




AMGLVFICVKNGNMRCTICI






BAN59727
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
44


A/duck/Mongolia/
NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



129/2010
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY



2010// HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



519661954
RKDPALIIWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS




PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCP




RYVKQESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQINPVKLSSGYKDVILWFSFGASCFILLAI




AMGLVFICVKNGNMRCTICI






AGQ80952
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
45


A/duck/Jiangxi/
NATETVERTSIPRICSKGKRAVDLGQCGLLGTITGPPQCDQFLEF



3096/2009
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY



2009// HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQTIKSYKNT



523788794
RKDPALIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSFVPS




PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHNGGTIISNLPFQNINSRAVGKCP




RYVKQESLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFTEVERQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




AMGLVFICVKNGNMRCTICI






AGQ80989
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
46


A/duck/Jiangxi/
NATETVERTSIPRICSKGKRAVDLGQCGLLGTITGPPQCDQFLEF



3257/2009
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY



2009// HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQTIKSYKNT



523788868
RKDPALIIWGIHHSGSTTEQTKLYGSGNKLITVGXSNYQQSFVPS




PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHNGGTIISNLPFQNINSRAVGKCP




RYVKQESLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFTEVERQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




AMGLVFICVKNGNMRCTICI






AGQ81043
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
47


A/chicken/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Rizhao/515/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEEMGFTY



2013// HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



523788976
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGR33894
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
48


A/chicken/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Rizhao/719b/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013// HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



524845213
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDRSKYREEAMQNRXXXXXXXXXXXXKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGR49399
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
49


A/chicken/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Jiangxi/
SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY



SD001/2013
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2013/05/03 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



525338528
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGR49495
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
50


A/chicken/
NATETVERTNIPRICSKGKMTVDLGQCGLLGTITGPPQCDQFLEF



Shanghai/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



S1358/2013
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2013/04/03
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



HA 525338689
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIKNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGR49506
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
51


A/chicken/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Shanghai/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



S1410/2013
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2013/04/03
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



HA 525338708
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGR49554
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
52


A/chicken/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Zhejiang/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



SD033/2013
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2013/04/11
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



HA 525338789
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGR49566
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
53


A/duck/Anhui/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



SC702/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/04/16 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



525338809
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDNRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGR49722
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
54


A/homing
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



pigeon/Jiangsu/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



SD184/2013
SEIRINGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2013/04/20 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



525339071
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGR49734
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
55


A/pigeon/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Shanghai/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



S1069/2013
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2013/04/02 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



525339091
PGARPQVNGLSGRIDFHWLMLNPNDTITFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGR49770
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
56


A/wild
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



pigeon/Jiangsu/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



SD001/2013
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2013/04/17 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



525339151
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGY41893
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
57


A/Huizhou/01/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



2013 2013/08/08
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



HA 552049496
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT




RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGY42258
FALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVNATETVE
58


A/mallard/
RTNVPRICSRGKRTVDLGQCGLLGTIXGPPQCDQFLEFSADLIIE



Sweden/91/2002
RREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTYSGIRTNG



2002/12/12 HA
AXSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRNDPALI



552052155
IWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSFVPSPGARPQV




NGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQ




SGVQIDANCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQES




LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQN




AQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFTEV




EKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLADSEMNKL




YERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKYR




EEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIAMGLVFM




CVKNGNMRCTICI






AHA11441
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVV
59


A/guinea
NATETVETANIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF



fowl/Nebraska/
DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY



17096/2011
SGIRTNGATSACRRSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNP



2011/04/10 HA
RNKPALIVWGVHHSGSATEQTKLYGSGSKLITVGSSKYQQSFTPS



557478572
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR




GESLGVQSDVPLDSGCEGDCFHKGGTIVSSLPFQNINPRTVGKCP




RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI




DNEFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT




YDHTQYRAESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI




AMGLVFICIKNGNMRCTICI






AHA11452
MNTQILALIACMLVGIKGDKICLGHHAVANGTKVNTLTERGIEVV
60


A/turkey/
NATETVETANIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF



Minnesota/
DADLIIERREGTDVCYPGKFTNEEPLRQILRGSGGIDKESMGFTY



32710/2011
SGIRTNGATSTCRRSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNP



2011/07/12
RNKPALIVWGVHHSGSATEQTKLYGSGSKLITVGSSKYQQSFTPS



HA 557478591
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR




GESLGVQSDVPLDSGCEGDCFHKGGTIVSSLPFQNINPRTVGKCP




RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFEMI




DNEFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT




YDHTQYRAESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI




AMGLVFICIKNGNMRCTICI






AHA11461
MNTQILALIACMLVGIKGDKICLGHHAVANGTKVNTLTERGIEVV
61


A/turkey/
NATETVETANIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF



Minnesota/
DADLIIERREGTDVCYPGKFTNEEPLRQILRGSGGIDKESMGFTY



31900/2011
SGIRTNGATSTCRRSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNP



2011/07/05
RNKPALIVWGVHHSGSATEQTKLYGSGSKLITVGSSKYQQSFTPS



HA 557478606
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR




GESLGVQSDVPLDSGCEGDCFHKGGTIVSSLPFQNINPRTVGKCP




RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI




DNEFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT




YDHTQYRAESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI




AMGLVFICIKNGNMRCTICI






AHK10585
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
62


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Guangdong/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



G1/2013
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2013/05/05 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



587680636
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGG53366
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
63


A/wild
NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



duck/Korea/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGLTY



CSM42-34/2011
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2011/03/
RRDPALIVWGIHHSGSSTEQTKLYGSGSKLITVGSSNYQQSFVPS



HA 459252887
PGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCP




RYVKQESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVRLSSGYKDVILWFSFGASCFILLAI




AMGLVFICVKNGNMRCTICI






AGG53377
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
64


A/wild
NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



duck/Korea/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGLTY



CSM42-1/2011
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2011/03/
RRDPALIVWGIHHSGSSTEQTKLYGSGSKLITVGSSNYQQSFVPS



HA 459252925
PGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCP




RYVKQESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVRLSSGYKDVILWFSFGASCFILLAI




AMGLVFICVKNGNMRCT






AGG53399
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
65


A/wild
NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



duck/Korea/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY



MHC39-26/2011
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2011/03/
RRDPALIVWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS



HA 459253005
PGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCP




RYVKQESLMLATGMKNVPEPPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




AMGLVFICVKNGNMRCTICI






AGG53432
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
66


A/wild
NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



duck/Korea/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY



MHC35-41/2011
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2011/03/
RRDPALIVWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS



HA 459253136
PGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCP




RYVKQESLMLATGMKNVPEPPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




AMGLVFICVKNGNMRCT






AGG53476
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
67


A/wild
NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



duck/Korea/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY



SH19-27/2010
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2010/12/
RRDPALIVWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS



HA 459253257
PGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCP




RYVKQESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




AMGLVFICVKNGNMRCTI






AGG53487
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
68


A/wild
NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



duck/Korea/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY



SH19-50/2010
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2010/01/
RRDPALIVWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS



HA 459253278
PGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCP




RYVKQESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




AMGLVFICVKNGNMRCTICI






AGG53520
QILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVNAT
69


A/wild
ETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQLLEFSAD



duck/Korea/
LIIERREGTDVCYPGKFVNEEALRQILRESGGIEKETMGFTYSGI



SH20-27/2008
RTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKD



2008/12/
PALIIWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPSPGA



HA 459253409
RPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLRGKS




MGIQSGVQVDANCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYV




KQESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYGF




RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNE




FTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLADSE




MNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDH




SKYREEAMQNRIQINPVKLSSGYKDVILWFSFGASCFILLAIAMG




LVFICVKNGNMR






AGL43637
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
70


A/Taiwan/1/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



2013 2013// HA
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



496297389
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT




RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGPSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIINNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGL97639
IACMLVGAKGDKICLGHHAVANGTKVNTLTERGIEVVNATETVET
71


A/mallard/
ANIKKLCTQGKRPTDLGQCGLLGTLIGPPQCDQFLEFDADLIIER



Minnesota/AI09-
REGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTYSGIRTNGA



3770/2009
TSACRRSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPALII



2009/09/12 HA
WGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFTPSPGARPQVN



505555371
GQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQS




DVPLDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTSL




LLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNA




QGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDNEFSEIE




QQIGNVINWTRDSMTELWSYNAELLVAMENQHTIDLADSEMNKLY




ERVRKQLRENAEEDGIGCFEIFHKCDDQCMESIRNNTYDHIQYRT




ESLQNRIQIDPVKLS






AGO02477
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
72


A/Xuzhou/1/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



2013 2013/04/25
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



HA 512403688
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT




RKSPALIVWGIHHSVSTAEQTKLYGSGSKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKSRNMRCTICI






AGR84942
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
73


A/Suzhou/5/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



2013 2013/04/12
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



HA 526304561
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT




RKSPALIVWGIHHSVSTAEQTKLYGSGSKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AGR84954
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
74


A/Nanjing/6/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



2013 2013/04/11
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



HA 526304594
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT




RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNRNMRCTICI






AGR84978
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
75


A/Wuxi/4/2013
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



2013/04/07 HA
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



526304656
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT




RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKSRNMRCTICI






AGR84990
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
76


A/Wuxi/3/2013
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



2013/04/07 HA
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



526304688
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT




RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKSRNMRCTICI






AGR85002
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
77


A/Zhenjiang/1/
NATETVERTNIPRICSKGKMTVDLGQCGLLGTITGPPQCDQFLEF



2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/04/07 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



526304708
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKSRNKRCTICI






AGR85026
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
78


A/Nanjing/2/
NATETVERTNIPRICSKGKMTVDLGQCGLLGTITGPPQCDQFLEF



2013 2013/04/05
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



HA 526304762
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT




RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKSRNMRCTICI






AGU02230
LVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGGEVVNATET
79


A/Zhejiang/
VERTNIPRICSKGKRTVDLGQCGLRGTITGPPQCDQFLEFSADLI



DTID-ZJU05/2013
IERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTYSGIRT



2013/04/
NGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA



HA 532808765
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPGARP




QVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMG




IQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQ




RSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRH




QNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFN




EVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADSEMD




KLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSK




YREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIVMGLV




FICVKNGNMRCT






AGU02233
FALIAIIPTNADKICLGHHAVSNGTKVNTLTERGGEVVNATETVE
80


A/Zhejiang/
RTNFPRICSKGKRTVDLGQCGLRGTITGPPQCDQFLEFSADLIIE



DTID-ZJU08/2013
RREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTYSGIRTNG



2013/04/
ATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNIRKSPALI



HA 532808788
VWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPGARPQV




NGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQ




SGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS




LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQN




AQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFNEV




EKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADSEMDKL




YERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKYR




EEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIVMGLVFI




CVKNGNMRCT






AGW82588
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
81


A/tree
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



sparrow/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



Shanghai/01/2013
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2013/05/09 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



546235348
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTIGI






AGW82600
ALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVNATETVER
82


A/Shanghai/
TNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEFSADLIIER



CN01/2013
REGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTYSGIRTNGA



2013/04/11 HA
TSACRRSRSSFYAEMKWLLSNTDNAAFPQMTKSYKNIRKSPALIV



546235368
WGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPGARPQVN




GLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQS




GVQVDANCEGDCYHSGGTIMSNLPFQNIDSRAVGKCPRYVKQRSL




LLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNA




QGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFNEVE




KQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADSEMDKLY




ERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKYRE




EAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIVMGLVFIC




VKNGNMRCTICI






AGW82612
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
83


A/Shanghai/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



JS01/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/04/03 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



546235388
RKNPALIVWGIHHSGSTAEQTKLYGSGNKLVTVGSSNYQQSFAPS




PGARTQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFTEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




AMGLVFICVKNGNMRCTICI






AHA11472
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVV
84


A/turkey/
NATETVETANVKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF



Minnesota/
DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY



31676/2009
SGIRTNGETSACRRSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNP



2009/12/08
RDKPALIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFTPS



HA 557478625
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR




GESLGVQSDVPLDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCP




RYVKQTSLLLATGMRNVPEKPKTRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITNKLNRLIDKTNQQFELI




DNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT




YDHTQYRKESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI




AMGLVFICIKNGNMRCTICI






AHA11483
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVV
85


A/turkey/
NATETVETANVKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF



Minnesota/
DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY



14135-2/2009
SGIRTNGATSACRRSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNP



2009/08/07 HA
RDKPALIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFTPS



557478644
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR




GESLGVQSDVPLDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCP




RYVKQTSLLLATGMRNVPEKPKTRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITSKLNRLIDKTNQQFELI




DNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT




YDHTQYRKESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI




AMGLVFICIKNGNMRCTICI






AHA11500
TQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVNA
86


A/Zhejiang/
TETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEFSA



DTID-ZJU10/2013
DLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTYSG



2013/10/14 HA
IRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRK



557478676
SPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPG




ARPPVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLRGK




SMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRY




VKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG




FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN




EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADS




EMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYD




HSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIVM




GLVFICVKN






AHA57050
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVV
87


A/turkey/
NATETVETANVKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF



Minnesota/
DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY



14659/2009
SGIRTNGATSACRRSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNP



2009/08/12
RDKPALIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFTPS



HA 558484427
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR




GESLGVQSDVPLDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCP




RYVKQTSLLLATGMRNVPEKPKTRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITSKLNRLIDKTNQQFELI




DNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRKQLRENAEEDGTGCFEIFHNCDDQCMESIRNNT




YDHTQYRKESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI




AMGLVFICIKNGNMRCTICI






AHA57072
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVV
88


A/turkey/
NATETVETANVKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF



Minnesota/
DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY



18421/2009
SGIRTNGATSACRRSGSSFYAEMKWLLSNSNDAAFPQMTKSYRNP



2009/09/09
RDKPALIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFTPS



HA 558484465
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR




GESLGVQSDVPLDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCP




RYVKQTSLLLATGMRNVPEKPKTRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI




DNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT




YDHTQYRKESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI




AMGLVFICIKNGNMRCTICI






AHD25003
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
89


A/Guangdong/02/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



2013 2013/10/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



HA 568260567
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT




RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNM






AHF20528
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
90


A/Hong
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Kong/470129/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/11/30
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



HA 570933555
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISSLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AHF20568
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
91


A/Shanghai/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



CN02/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/04/02 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



570933626
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIMSNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AHH25185
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
92


A/Guangdong/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



04/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIEKEAMGFTY



2013/12/16 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



576106234
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AHJ57411
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
93


A/Shanghai/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



PD-01/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/01/17 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



585478041
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVSS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCKGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRIIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AHJ57418
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
94


A/Shanghai/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



PD-02/2014
SADLIIERREGSDICYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/01/17 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



585478256
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLK




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRIIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AHK10800
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
95


A/Shanghai/01/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/01/03 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



587681014
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRIIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AHM24224
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
96


A/Beijing/3/2013
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



2013/04/16
SADLIIERREGSDVCYPGKEVKEEALRQILRESGGIDKEAMGFTY



HA 594704802
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT




RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AHN96472
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
97


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Shanghai/PD-CN-
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



02/2014
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2014/01/21 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



602701641
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AHZ39686
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
98


A/Anhui/DEWH72-
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



01/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013// HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDDAAFPQMTKSYKNT



632807036
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AHZ39710
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
99


A/Anhui/DEWH72-
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



03/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013// HA
SGIRTDGATSACRRSGSSFYAEMKWLLSNTDDAAFPQMTKSYKNT



632807076
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AHZ39746
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
100


A/Anhui/DEWH72-
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



06/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013// HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



632807136
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGERPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AHZ41929
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
101


A/mallard/
NATETVERTNVPRICSRGKRTVDLGQCGLLGTITGPPQCDQFLEF



Sweden/1621/2002
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY



2002/12/12 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



632810949
RNDPALIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSFVPS




PGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQIDANCEGDCYHSGGTIISNLPFQNINSRAVGKCP




RYVKQESLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




AMGLVFMCVKNGNMRCTICI






AHZ42537
MNTQILAFIACMLVGAKGDKICLGHHAVANGTKVNTLTERGIEVV
102


A/mallard/
NATETVETANIKKLCTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF



Minnesota/
DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY



AI09-3770/2009
SGIRTNGATSACRRSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNP



2009/09/12 HA
RNKPALIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFTPS



632811964
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR




GESLGVQSDVPLDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCP




RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI




DNEFSEIEQQIGNVINWTRDSMTELWSYNAELLVAMENQHTIDLA




DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT




YDHTQYRTESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI




AMGLVFICIKNGNMRCTICI






AHZ42549
MNTQILAFIACMLVGVRGDKICLGHHAVANGTKVNTLTEKGIEVV
103


A/ruddy
NATETVESANIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF



turnstone/
DSDLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY



Delaware/AI00-
SGIRTNGATSACRRLGSSSFYAEMKWLLSNSDNAAFPQMTKSYRN



1538/2000
PRNKPALIIWGVHHSGSANEQTKLYGSGNKLITVGSSKYQQSFTP



2000/05/20 HA
SPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFF



632811984
RGESLGIQSDVPLDSSCGGDCFHSGGTIVSSLPFQNINPRTVGKC




PRYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDG




WYGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFEL




MDNEFNEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDL




ADSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNN




TYDHTQYRTESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLA




IAMGLIFICIKNGNMRCTICI






AID70634
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
104


A/Shanghai/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Mix1/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/01/03 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



660304650
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRIIEKTNQQFELI




DNEFNEVEKQISNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AIN76383
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTERGVEVV
105


A/Zhejiang/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



LS01/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/08 HA
SGIRTNGITSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



684694637
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AIU46619
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
106


A/chicken/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Zhejiang/DTID-
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



ZJU06/2013
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2013/12/
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



HA 699978931
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVEVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AIU47013
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
107


A/chicken/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Suzhou/040201H/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013 2013/04/
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



HA 699979673
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDMILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ90490
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
108


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Shenzhen/742/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/12/10 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755178094
RRSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ90526
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
109


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Shenzhen/898/2013
SADLIIERREGSDICYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/12/09 HA
SGIRANGATSACKRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755178154
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISSLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSRGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ90538
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
110


A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



chicken/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



Shenzhen/918/2013
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2013/12/09 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



755178174
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ90576
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
111


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Shenzhen/1665/2013
SADLIIERREGSDICYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/12/12 HA
SGIRANGATSACKRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755178238
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSRGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ90588
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
112


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Shenzhen/2110/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/12/13 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755178258
RRSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSIGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ90661
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
113


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/2912/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/12/18 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755178380
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ90673
MNTQILVFALTAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
114


A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



chicken/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



Dongguan/3049/2013
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2013/12/18 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



755178400
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ90795
MNTQILVFALIAIIPTNADKICLGHHAVPNGTKVNTLTERGVEVV
115


A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



chicken/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



Dongguan/3281/2013
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2013/12/18 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



755178604
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ90891
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
116


A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



chicken/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



Dongguan/3520/2013
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2013/12/19 HA
RKXPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



755178764
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ90951
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
117


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/3544/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/12/19 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYRNT



755178864
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ91035
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
118


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Shenzhen/3780/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/12/19 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755179004
RRSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDNRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ91155
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
119


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/4037/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/12/19 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755179204
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ92005
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
120


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Shenzhen/801/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/12/09 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755180629
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSRGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ94254
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
121


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/1374/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/21 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755184382
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPERASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ94606
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
122


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/191/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY



2014/02/20 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755184968
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ96552
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
123


A/chicken/
NATETVERTNIPRICSKGKKTIDLGQCGLLGTITGPPQCDQFLEF



Jiangxi/12206/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/03/16 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755188219
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHNKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ96684
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKINTLTERGVEVV
124


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Jiangxi/13207/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/03/30 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755188439
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ96732
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
125


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Jiangxi/13223/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/03/30 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755188519
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJK00354
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
126


A/duck/Zhejiang/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



LS02/2014
SADLIVERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/01/12 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755194469
RKDPALIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSFVPS




PGARPLVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNINSRAVGKCP




RYVKQESLLLATGMKNVPEVPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQVIGKLNRLIEKTNQQFELI




DHEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA




DSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ91264
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
127


A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



chicken/Dongguan/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



4129/2013
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2013/12/19 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



755179386
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLMEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ91314
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
128


A/chicken/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Shaoxing/2417/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/10/20 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755179470
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPPVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ91402
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
129


A/chicken/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Huzhou/4045/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/10/24 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755179618
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKEVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ91476
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
130


A/chicken/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Huzhou/4076/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY



2013/10/24 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755179743
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSRGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ91725
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
131


A/chicken/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Shaoxing/5201/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/10/28 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755180161
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ91885
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
132


A/Shenzhen/SP4/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/01/16 HA
SGIRANGVTSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755180429
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSRGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ91909
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
133


A/Shenzhen/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



SP26/2014
SADLIIERREGSDICYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/01/20 HA
SGIRANGATSACKRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755180469
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISSLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDGCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSRGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ91945
MNTQILAFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
134


A/Shenzhen/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



SP38/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/01/22 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755180529
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIGGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ91957
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
135


A/Shenzhen/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



SP44/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/01/23 HA
SGIRANGTTSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755180549
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISSLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ91969
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
136


A/Shenzhen/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



SP48/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/01/23 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755180569
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ91993
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
137


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/4119/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/12/19 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755180609
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLLGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFTLLAI




VMGLVFICVKNGNMRCTICI






AJJ92031
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
138


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/4064/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2013/12/19 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755180672
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVESSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ92967
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTERGVEVV
139


A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



chicken/Jiangxi/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



9469/2014
SGIRTNGVISACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2014/02/16 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



755182232
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ93027
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTERGVEVV
140


A/chicken/Jiangxi/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



9558/2014
SADLIIERREGSDVCYPGKEVKEEALRQILRESGGIDKEAMGFTY



2014/02/16 HA
SGIRTNGVISACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755182332
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ93051
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTERGVEVV
141


A/chicken/Jiangxi/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



10573/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/18 HA
SGIRTNGVISACRRSGSSFYAEMKWLLSNIDDAAFPQMTKSYKNT



755182372
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ93845
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
142


A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



chicken/Dongguan/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



157/2014
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2014/02/20 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



755183695
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ93857
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
143


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/169/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY



2014/02/20 HA
SGIRTNGATSACMRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755183715
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ93869
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
144


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTVTGPPQCDQFLEF



Dongguan/173/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/20 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755183735
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ93881
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
145


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTVTGPPQCDQFLEF



Dongguan/189/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/20 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755183755
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




KYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ93907
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
146


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/449/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/20 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755183799
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPERASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ93931
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
147


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/536/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY



2014/02/20 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755183839
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDADCEGDCYHSGGTIISKLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ93943
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
148


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/568/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIEKEAMGFTY



2014/02/20 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755183859
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSGGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ93979
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
149


A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTVTGPPQCDQFLEF



chicken/Dongguan/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



656/2014
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2014/02/20 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



755183919
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFGLI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ94134
MNTQILVLALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
150


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/1051/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY



2014/02/21 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755184182
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVXLSXGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ94158
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
151


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/1075/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/21 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755184222
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPERASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYRGEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ94182
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
152


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/1177/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/21 HA
SGIRTNGATSACKRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755184262
RKSPALIVWGIHHSVSIAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ94194
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
153


A/silkie
NATETVERTNIPRICSKGKKTIDLGQCGLLGTITGPPQCDQFLEF



chicken/Dongguan/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



1264/2014
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2014/02/21 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



755184282
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPERASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFKHQNAQGEGTAADYKSTQSAIDQVIGKLNRLIEKTNQQFELI




DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYRGEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFMLLAI




VMGLVFICVKNGNMRCTICI






AJJ94206
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
154


A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



chicken/Dongguan/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



1268/2014
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2014/02/21 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



755184302
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPERASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISDLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ94344
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
155


A/silkie
NSTETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



chicken/Dongguan/
SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY



1451/2014
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2014/02/21 HA
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



755184532
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRTVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ94356
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
156


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/1456/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/21 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755184552
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPERASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ94396
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
157


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/1494/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/21 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755184618
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPETPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ94754
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
158


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/748/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIEKEAMGFTY



2014/02/20 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755185215
RKSPALIVWGIHHSVSNAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSGGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ94838
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
159


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/835/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/20 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755185356
RKSPALIVWGIHHSASTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFGFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ94862
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
160


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/843/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIEKEAMGFTY



2014/02/20 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755185396
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSGGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ94886
MNTQILAFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
161


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/851/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/20 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755185436
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ94910
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
162


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/874/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/20 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755185476
RKSPALIVWGIHHSASTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ94959
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
163


A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



chicken/Dongguan/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



967/2014
SGIRANGATSACXRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2014/02/21 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



755185558
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ95048
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
164


A/chicken/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/1009/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/21 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755185708
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPETPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ95171
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
165


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/1314/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/21 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755185913
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVIFNFNGAFIAPERASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ95227
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
166


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/1382/2014
SADLIIERREGSDICYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/21 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755186006
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPERASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ95251
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
167


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/1401/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/21 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755186046
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYKRVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ95346
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
168


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/1548/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/21 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755186206
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYKRVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHNKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ95382
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
167


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/1690/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY



2014/02/21 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755186266
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSIGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ95464
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
170


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Shenzhen/138/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/19 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755186404
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPERASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYRGEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFMLLAI




VMGLVFICVKNGNMRCTICI






AJJ95572
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
171


A/chicken/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Dongguan/1100/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIEKEAMGFTY



2014/02/21 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755186584
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSGGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ95584
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
172


A/silkie
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



chicken/Dongguan/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



1519/2014
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2014/02/21 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



755186604
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPERASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYRGEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFMLLAI




VMGLVFICVKNGNMRCTICI






AJJ95596
MNTQILAFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
173


A/Shenzhen/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



SP58/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/01/25 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755186624
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ95620
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
174


A/Shenzhen/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



SP75/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/15 HA
SGIRTNGSTSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755186664
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAV




VMGLVFICVKNGNMRCTICI






AJJ95632
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
175


A/Shenzhen/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



SP62/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/05 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNATFPQMTKSYKNT



755186684
RKSPALIIWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ96720
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
176


A/chicken/Jiangxi/
NATETVERTTIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



13220/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/03/30 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755188499
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSRGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ96817
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTERGVEVV
177


A/chicken/Jiangxi/
NATEIVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



9513/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/02/16 HA
SGIRTNGVISACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755188661
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ96841
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
178


A/Shenzhen/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



SP139/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY



2014/04/02 HA
SGIRTNGATSTCRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755188701
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRACFLR




GKSMGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVERQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ96889
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
179


A/chicken/
NATETVERIXIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Jiangxi/13496/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKXAMGFTY



2014/04/11 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755188781
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSXGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ96901
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
180


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Jiangxi/13502/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/04/11 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755188801
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSXGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ96925
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
181


A/chicken/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Jiangxi/13513/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/04/11 HA
NGIRINGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755188841
RKSPAIIVWGIHHTVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDLHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKINQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHRKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ97267
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
182


A/chicken/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Jiangxi/13252/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/03/30 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755189411
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ97291
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
183


A/chicken/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Jiangxi/13493/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/04/06 HA
NGIRINGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755189451
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKINQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHRKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ97331
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
184


A/chicken/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Jiangxi/13512/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/04/06 HA
NGIRINGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755189517
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSIGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKINQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHRKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ97373
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
185


A/chicken/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Jiangxi/13521/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/04/06 HA
NGIRINGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755189587
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPXRASFLR




GKSXGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKINQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHRKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ97443
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
186


A/chicken/
NATETVERTTIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Jiangxi/13530/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/04/06 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755189702
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSRGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ97582
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
187


A/chicken/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Jiangxi/14023/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/04/13 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755189933
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKINQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHRKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ97697
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
188


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Jiangxi/14517/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/04/20 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755190125
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCDGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ97709
MNTQILVFALIAIIPANADKICLGHHAVSNGTKVNTLTERGVEVV
189


A/chicken/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



Jiangxi/14518/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/04/20 HA
NGIRINGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755190145
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGNCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKINQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHRKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ97745
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
190


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Jiangxi/14554/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/04/20 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755190205
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELM




DNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ97757
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
191


A/chicken/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



Shantou/2537/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY



2014/04/16 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755190225
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ97841
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
192


A/duck/Jiangxi/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



15044/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/04/27 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755190365
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKINQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHRKYREEAMQNRIQIDPVRLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ97899
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
193


A/chicken/Jiangxi/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF



15524/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/05/05 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755190462
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKINQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHRKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFMCVKNGNMRCTICI






AJJ97925
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
194


A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



chicken/Shantou/
SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY



2050/2014
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



2014/03/25 HA
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS



755190506
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEVPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ97973
MNTQILVFALISIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
195


A/chicken/Shantou/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



4325/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY



2014/07/01 HA
SGIRTNGVTSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755190586
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQRSLLLATGMKNVPEVPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI






AJJ97998
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTERGVEVV
196


A/chicken/Shantou/
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF



4816/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY



2014/07/22 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT



755190628
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS




PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR




GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP




RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW




YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELV




DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA




DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT




YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI




VMGLVFICVKNGNMRCTICI
















TABLE 15







H10 Hemagglutinin Amino Acid Sequences










SEQ





ID
Accession No/

SEQ


 NO:
Strain/Protein
Amino Acid Sequence
ID NO:














AAM19228
ACVLVEAKGDKICLGHHAVVNGTKVNTLTEKGIEVVN
197



A/turkey/
ATETVETANIGKICTQGKRPTDLGQCGLLGTLIGPPQ




Minnesota/
CDQFLEFESDLIIERREGNDVCYPGKFTNEESLRQIL




38429/1988 
RGSGGIDKESMGFTYSGIITNGATSACRRSGSSFYAE




1988// HA
MKWLLSNSDNAAFPQMTKSYRNPRNKPALIVWGIHHS




20335017
GSTTEQTKLYGSGNKLITVESSKYQQSFTPSPGARPQ





VNGESGRIDFHWMLLDPNDTVTFTFNGAFIAPDRASF





FKGESLGVQSDVPLDSSCGGDCFHSGGTIVSSLPFQN





INPRTVGKCPRYVKQPSLLLATGMRNVPENPKTRGLF





GAIAGFIEKDGGSHYG







AAY46211
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL
198



A/mallard/
TERGVEVVNATETVERTNVPRICSRGKRTVDLGQCGL




Sweden/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




91/2002
NEEALRQILRESGGIDKETMGFTYSGIRTNGAPSACR




2002// HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRNDPA




66394828
LIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSF





VPSPGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQIDANCEGDCYHSGGT





IISNLPFQNINSRAVGKCPRYVKQESLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIAMGLVFMCVKNGNMR





CTICI







ABI84694
MNTQILVFIACVLVEAKGDKICLGHHAVVNGTKVNTL
199



A/turkey/
TEKGIEVVNATETVETANIGKICTQGKRPTDLGQCGL




Minnesota/1/1988
LGTLIGPPQCDQFLEFESDLIIERREGNDVCYPGKFT




1988/07/13 HA
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR




115278573
RSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPA





LIVWGIHHSGSTTEQTKLYGSGNKLITVGSSKYQQSF





TPSPGARPQVNGQSGRIDFHWMLLDPNDTVTFTFNGA





FIAPDRASFFKGESLGVQSDVPLDSSCGGDCFHSGGT





IVSSLPFQNINPRTVGKCPRYVKQPSLLLATGMRNVP





ENPKTRGLFGAIAGFIENGWEGLIDGWYGFKHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN





EFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH





KCDDQCMESIRNNTYDHAQYRAESLQNRIQIDPVKLS





SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR





CTICI







ABS89409
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTL
200



A/blue-winged
TERGIEVVNATETVETANIKKICTQGKRPTDLGQCGL




teal/Ohio/566/
LGTLIGPPQCDQFLEFDTDLIIERREGTDVCYPGKFT




2006 2006// HA
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR




155016324
RSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPA





LIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSF





TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA





FIAPDRASFERGESLGVQSDVPLDSGCEGDCFHSGGT





IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP





ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN





EFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH





KCDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVRLS





SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR





CTICI







ACD03594
MNTQILAFIACMLVGVRGDKICLGHHAVANGTKVNTL
201



A/ruddy
TEKGIEVVNATETVESANIKKICTQGKRPTDLGQCGL




turnstone/DE/
LGTLIGPPQCDQFLEFDSDLIIERREGTDVCYPGKFT




1538/2000
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR




2000// HA
RLGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPA




187384848
LIIWGVHHSGSANEQTKLYGSGNKLITVGSSKYQQSF





TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA





FIAPDRASFERGESLGIQSDVPLDSSCGGDCFHSGGT





IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP





ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELMDN





EFNEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH





KCDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLS





SGYKDIILWFSFGASCFLLLAIAMGLIFICIKNGNMR





CTICI







BAH22785
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL
202



A/duck/Mongolia/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




119/2008
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2008// HA
NEEALRQILRESGGIGKETMGFTYSGIRTNGATSACR




223717820
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKDPA





LIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSF





VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHNGGT





IISNLPFQNINSRTVGKCPRYVKQESLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIERTNQQFELIDN





EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





NGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR





CTICI







CAY39406
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL
203



A/Anas crecca/
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL




Spain/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




1460/2008
NEEALRQILRESGGIDKETMGFTYSGIRTNGATSACR




2008/01/26 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKDPA




254674376
LIIWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSF





VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFTEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR





CTICI







ACX53683
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL
204



A/goose/Czech
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL




Republic/1848-
LGTITGPPQCDQFLEFSADLIIERRGGSDVCYPGKFV




K9/2009
NEEALRQILRESGGIDKETMGFTYSGIRTNGATSACR




2009/02/04 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKDPA




260907763
LIIWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSF





VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLKGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP





ELPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQINPVKLS





SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR





CTICI







ACZ48625
MNTQILVFIACVLVEAKGDKICLGHHAVVNGTKVNTL
205



A/turkey/
TEKGIEVVNATETVETANIGKICTQGKRPTDLGQCGL




Minnesota/38429/
LGTLIGPPQCDQFLEFESDLIIERREGNDVCYPGKFT




1988 1988// HA
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR




269826341
RSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPA





LIVWGIHHSGSTTEQTKLYGSGNKLITVGSSKYQQSF





TPSPGARPQVNGQSGRIDFHWMLLDPNDTVTFTFNGA





FIAPDRASFFKGESLGVQSDVPLDSSCGGDCFHSGGT





IVSSLPFQNINPRTVGKCPRYVKQPSLLLATGMRNVP





ENPKTRGLFGAIAGFIENGWEGLIDGWYGFKHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFEL







ADC29485
STQSAIDQITGKLNRLIEKTNQQFELIDNEFTEVEKQ
206



A/mallard/Spain/
IGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLADS




08.00991.3/
EMNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMA




2005 2005/11/
SIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVIL




HA 284927336
WFSFGASCFILL







ADK71137
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTL
207



A/blue-winged
TERGIEVVNATETVETANIKKICTQGKRPTDLGQCGL




teal/Guatemala/
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT




CIP049-
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR




01/2008
RSGSSSYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPA




2008/02/07 HA
LIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSF




301333785
TPSPGIRPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA





FIAPDRASFLRGKSLGIQSDVPLDSGCEGDCFHSGGT





IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP





ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIDKTNQHFELIDN





EFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH





KCDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLS





SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR





CTICI







ADK71148
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTL
208



A/blue-winged
TERGIEVVNXTETVETANIKKICTHGKRPTDLGQCGL




teal/Guatemala/
LGTLIGPPQCDRFLEFDADLIIERREGTDVCYPGKFT




CIP049-
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR




02/2008
RSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPA




2008/03/05 HA
LIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSF




301333804
TPSPGIRPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA





FIAPDRASFLRGKSLGIQSDVPLDSGCEGDCFHSGGT





IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP





ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN





EFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH





KCDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLS





SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR





CTICI







ADN34727
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL
209



A/goose/Czech
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL




Republic/1848-
LGTITGPPQCDQFLEFSADLIIERRGGSDVCYPGKFV




T14/2009
NEEALRQILRESGGIDKETMGFTYSGIRINGXTSACR




2009/02/04 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKDPA




307141869
LIIWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSF





VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLKGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP





ELPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQINPVKLS





SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR





CTICI







AEK84760
PAFIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSG
210



A/wild
GTIISNLPFQNINSRAVGKCPRYVKQESLMLATGMKN




bird/Korea/A14/
VPELPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNA




2011 2011/02/
QGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI




HA 341610308
DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAME





NQHTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEI





FHKCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVK





LSSGYKDVILWFSFGASCFILLAIAMGLVFICVKNGN





MRCTICI







AEK84761
ILVFALVAIIPTNANKIGLGHHAVSNGTKVNTLTERG
211



A/wild
VEVFNATETVERTNVPRICSKGKKTVDLGQCGLRGTI




bird/Korea/A3/
TGPPQCDQFLKFSPDLIIERQKGSDVCYPGKFVNEKP




2011 2011/02/
LRQILRESGGIDKETMGFAYNGIKTNGPPIACRKSGS




HA 341610310
SFYAKMKWLLSNTDKAAFPQMTKSYKNTRRNPALIVW





GIHHSGSTTKQTKLYGIGSNLITVGSSNYQQSFVPSP





GARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIPP





DRASFLRGKSMGIQSGVQVDASCEGDCYHSGGTIISN





LPFQNINSRAVGKCPRYVKQESLMLATGMKNVPELPK





GKGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTA





ADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFTE





VEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTID





LADSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDD





DCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYK





DVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTIC





I







AEK84763
ILVFALVAIIPTNANKIGLGHHAVSNGTKVNTLTERG
212



A/wild
VEFFNATETVEPINVPRICSKGKKTVDLGQCGLLGTI




bird/Korea/A9/
TGPPQCDQFLEFSADLIIERREGSDVCYPGKFVNEKA




2011 2011/02/
LRQILRESGGIDKETMGFAYSGIKTNGPPIACRKSGS




HA 341610314
SFYAKMKWLLSNTDKAAFPQMTKSYKNTRRDPALIVW





GIHHSGSTIKQINLYGIGSNLITVGSSNYQQSFVPSP





GARPQVNGQSGRIDFHWLILNPNDTVTFIFNGAFIAP





DRASFLIGKSMGIQSGVQVDASCEGDCYHSGGTIISN





LPFQNINSRAVGKCPRYVKQESLMLATGMKNVPELPK





GRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTA





ADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFTE





VEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTID





LADSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDD





DCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYK





DVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTIC





I







AEK84765
LVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGV
213



A/spot-billed
EVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTIT




duck/Korea/447/
GPPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEAL




2011 2011/04/
RQILRESGGIDKETMGFTYSGIRTNGATSACRRSGSS




HA 341610318
FYAEMKWLLSNTDNAAFPQMTKSYKNTRRDPALIVWG





IHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPSPG





ARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPD





RASFLRGKSMGIQSGVQVDASCEGDCYHSGGTIISNL





PFQNINSRAVGKCPRYVKQESLMLATGMKNVPEPPKG





RGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTAA





DYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFTEV





EKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDL





ADSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDD





CMARIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKD





VILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI







AEM98291
SILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER
214



A/wild
GVEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGT




duck/Mongolia/
ITGPPQCDQFLEFSADLIIERREGSDVCYPGKFVNEE




1-241/2008
ALRQILRESGGIDKETMGFTYSGIRTNGATSACRRSG




2008/04/ HA
SSFYAEMKWLLSNTDNAAFPQMTKSYKNIRKDPALII




344196120
WGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS





PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIA





PDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGSIIS





NLPFQNINSRAVGKCPRYVKQESLMLATGMKNVPELP





KGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGT





AADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFT





EVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTI





DLADSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCD





DDCMASIRNNTYDHSKYREEAMQNRIQINPVKLSSGY





KDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTI







AFM09439
QILAFIACMLIGAKGDKICLGHHAVANGTKVNTLTER
215



A/emperor
GIEVVNATETVETVNIKKICTQGKRPTDLGQCGLLGT




goose/Alaska/
LIGPPQCDQFLEFDADLIIERRKGTDVCYPGKFTNEE




44063-061/2006
SLRQILRGSGGIDKESMGFTYSGIRTNGATSACRRSG




2006/05/23 HA
SSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPALII




390535062
WGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFVPS





PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIA





PERASFFRGESLGVQSDVPLDSGCEGDCFHSGGTIVS





SLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVPENP





KTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGT





AADYKSTQSAIDQITGKLNRLIDKTNQQFELIDNEFS





EIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTI





DLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCD





DQCMESIRNNTYDHTQYRTESLQNRIQINPVKLSSGY





KDIILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTI





CI







AFV33945
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTL
216



A/guinea
TERRIEVVNATETVETANIKKICTQGKRPTDLGQCGL




fowl/Nebraska/
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT




17096-1/2011
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR




2011/04/05 HA
RSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNPRNKPA




409676820
LIVWGVHHSGSATEQTKLYGSGSKLITVGSSKYQQSF





TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA





FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHKGGT





IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP





ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN





EFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH





KCDDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLS





SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR





CTICI







AFV33947
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTL
217



A/goose/
TERGIEVVNATETVETANIKKICTQGKRPTDLGQCGL




Nebraska/17097-
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT




4/2011
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR




2011/04/05 HA
RSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPA




409676827
LIVWGVHHSASATEQTKLYGSGSKLITVGSSKYQQSF





TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA





FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHKGGT





IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP





ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN





EFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH





KCDDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLS





SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR





CTICI







AFX85260
MNTQILAFIACMLIGINGDKICLGHHAVANGTKVNTL
218



A/ruddy
TERGIEVVNATETVETANIKRICTQGKRPIDLGQCGL




turnstone/
LGTLIGPPQCDQFLEFDSDLIIERREGTDVCYPGKFT




Delaware
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACI




Bay/220/1995
RLGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPA




1995/05/21 HA
LIIWGVHHSGSANEQTKLYGSGNKLITVGSSKYQQSF




423514912
TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA





FIAPDRASFFRGESLGVQSDVPLDSSCGGDCFHSGGT





IVSSLPFQNINPRTVGRCPRYVKQTSLLLATGMKNVP





ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN





EFNEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH





KCDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLS





SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR





CTICI







AGE08098
MNTQILTLIACMLIGAKGDKICLGHHAVANGTKVNTL
219



A/northern
TERGIEVVNATETVETANIKKICTQGKRPTDLGQCGL




shoverl/
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT




Mississippi/
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR




11OS145/2011
RSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPA




2011/01/08 HA
LIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSF




444344488
TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA





FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHNGGT





IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP





ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN





EFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH





KCDDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLS





SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR





CTICI







AGI60301
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
220



A/Hangzhou/1/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




2013 2013/03/24
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




HA 475662454
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR





RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGISGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGI60292
MNTQILVFALIAIIPANADKICLGHHAVSNGTKVNTL
221



A/Shanghai/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




4664T/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/03/05 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




476403560
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCHHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGJ72861
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
222



A/chicken/
TERGGEVVNATETVERTNIPRICSKGKKTVDLGQGGP




Zhejiang/DTID-
RGTITGPPQCDQFLEFSADLIMERREGSDVCYPGKFV




ZJU01/2013
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




2013/04/
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




HA 479280294
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGJ73503
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
223



A/Nanjing/1/
TERGVEVVNATETVERTNIPRICSKGKMTVDLGQCGL




2013 2013/03/28
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




HA 479285761
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR





RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







BAN16711
MNIQVLVFALMAIIPTNADKICLGHHAVSNGTKVNTL
224



A/duck/Gunma/
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL




466/2011 2011//
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




HA 482661571
NEEALRQILRESGGIDKETMGFTYSGIRINGITSACR





RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRDPA





LIAWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSF





VPSPGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSGGT





IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP





ELPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRRQLRENAEEDDTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR





CTICI







AGK84857
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
225



A/Hangzhou/2/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




2013 2013/04/01
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




HA 485649824
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR





RSGSSFYAEMKWLLSNTDNAAFPQIIKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGL44438
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
226



A/Shanghai/02/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/03/05 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




496493389
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGL33692
GMIDGWYGFRHQNAQGEGTAADYKSTQSAIDQITGKL
227



A/Shanghai/
NRLIEKTNQQFELIDNEFTEVEKQIGNVINWTRDSIT




4655T/2013
EVWSYNAELLVAMENQHTIDLADSEMDKLYERVKRQL




2013/02/26 HA
RENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKYR




491874175
EEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLA





IAMGLVFICVKNGNMRCTICI







AGL33693
GMIDGWYGFRHQNAQGEGTAADYKSTQSAIDQITGKL
228



A/Shanghai/
NRLIEKTNQQFELIDNEFNEVEKQIGNVINWTRDSIT




4659T/2013
EVWSYNAELLVAMENQHTIDLADSEMDKLYERVKRQL




2013/02/27 HA 
RENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKYR




491874186
EEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLA





IVMGLVFICVKNGNMRCTICI







AGL95088
VFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVE
229



A/Taiwan/
VVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITG




S02076/2013
PPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALR




2013/04/22 HA
QILRESGGIDKEAMGFTYSGIRTNGATSACRRSGSSF




501485301
YAEMKWLLSNTDNAAFPQMTKSYKNTRKSPALIVWGI





HHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPGA





RPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDR





ASFLRGKSMGIQSGVQVDANCEGDCYHSGGTIISNLP





FQNIDSRAVGKCPRYVKQRSLLLATGMKNVPEIPKGR





GLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTAAD





YKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFNEVE





KQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA





DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDC





MASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDV





ILWFSFGASCFILLAIVMGLVFICVKNGNMR







AGL95098
LVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGV
230



A/Taiwan/
EVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTIT




T02081/2013
GPPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEAL




2013/04/22 HA
RQILRESGGIDKEAMGFTYSGIRTNGATSACRRSGSS




501485319
FYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPALIVWG





IHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPG





ARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPD





RASFLRGKSMGIQSGVQVDANCEGDCYHSGGTIISNL





PFQNIDSRAVGKCPRYVKQRSLLLATGMKNVPEIPKG





RGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTAA





DYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFNEV





EKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDL





ADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDD





CMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKD





VILWFSFGASCFILLAIVMGLVFICVKNGNMRCT







AGM53883
GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKT
231



A/Shanghai/
NQQFELIDNEFNEVEKQIGNVINWTRDSITEVWSYNA




5083T/2013
ELLVAMENQHTIDLADSEMDKLYERVKRQLRENAEED




2013/04/20 HA
GTGCFEIFHKCDDDCMASIRNNTYDHSKYREEAMQNR




507593986
IQIDPVKLSSGYKDVILWFSFGASCFILLAIVMGLVF





ICVKNGNMRCT







AGM53884
AQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFEL
232



A/Shanghai/
IDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAM




5180T/2013
ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFE




2013/04/23 HA
IFHKCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPV




507593988
KLSSGYKDVILWFSFGASCFILLAIVMGLVFICVKNG





NMRCTICI







AGM53885
QNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF
233



A/Shanghai/
ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLV




5240T/2013
AMENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGC




2013/04/25 HA
FEIFHKCDDDCMASIRNNTYDHSKYREEAMQNRIQID




507593990
PVKLSSGYKDVILWFSFGASCFILLAIVMGLVFICVK





NGNMRCT







AGM53886
NAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFE
234



A/Shanghai/
LIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVA




4842T/2013
MENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCF




2013/04/13 HA
EIFHKCDDDCMASIRNNTYDHSKYREEAMQNRIQIDP




507593992
VKLSSGYKDVILWFSFGASCFILLAIVMGLVFICVKN





GNMRCT







AGM53887
NAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFE
235



A/Shanghai/
LIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVA




4701T/2013
MENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCF




2013/04/06 HA
EIFHKCDDDCMASIRNNTYDHSKYREEAMQNRIQIDP




507593994
VKLSSGYKDVILWFSFGASCFILLAIVMGLVFICVKN





GNMRCTIC







AGN69462
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
236



A/Wuxi/2/2013
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




2013/03/31 HA
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




511105778
NEEALRQILRESGGIDKEAMGFTYSGIRTNGSTSACR





RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGSKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGN69474
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
236



A/Wuxi/1/2013
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




2013/03/31 HA
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




511105798
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR





RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLINGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGO51387
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
238



A/Jiangsu/2/
TERGVEVVNATETVERTNIPRICSKGKMTVDLGQCGL




2013 2013/04/20
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




HA 514390990
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR





RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYRXEAMXBXIQIDPVKLS





SGYKDVXJWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







BAN59726
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL
239



A/duck/Mongolia/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




147/2008
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2008/08/29 HA
NEEALRQILRESGGIGKETMGFTYSGIRTNGATSACR




519661951
RSRSSFYAEMKWLLSNTDNAAFPQMTRSYKNTRKDPA





LIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSF





VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHNGGT





IISNLPFQNINSRTVGKCPRYVKQESLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIERTNQQFELIDN





EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





NGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR





CTICI







BAN59727
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL
240



A/duck/Mongolia/
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL




129/2010
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2010// HA
NEEALRQILRESGGIDKETMGFTYSGIRTNGATSACR




519661954
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKDPA





LIIWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSF





VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSGGT





IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP





ELPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQINPVKLS





SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR





CTICI







AGQ80952
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL
241



A/duck/Jiangxi/
TERGVEVVNATETVERTSIPRICSKGKRAVDLGQCGL




3096/2009
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2009// HA
NEEALRQILRESGGIDKETMGFTYSGIRTNGATSACR




523788794
RSGSSFYAEMKWLLSNTDNAAFPQTTKSYKNTRKDPA





LIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSF





VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHNGGT





IISNLPFQNINSRAVGKCPRYVKQESLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFTEVERQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR





CTICI







AGQ80989
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL
242



A/duck/Jiangxi/
TERGVEVVNATETVERTSIPRICSKGKRAVDLGQCGL




3257/2009
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2009// HA
NEEALRQILRESGGIDKETMGFTYSGIRTNGATSACR




523788868
RSGSSFYAEMKWLLSNTDNAAFPQTTKSYKNTRKDPA





LIIWGIHHSGSTTEQTKLYGSGNKLITVGXSNYQQSF





VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHNGGT





IISNLPFQNINSRAVGKCPRYVKQESLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFTEVERQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR





CTICI







AGQ81043
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
243



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




Rizhao/515/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013// HA
NEEALRQILRESGGIDKEEMGFTYSGIRTNGATSACR




523788976
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGR33894
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
244



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




Rizhao/719b/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013// HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




524845213
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDRSKYREEAMQNRXXXXXXXXX





XXXKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGR49399
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
245



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




Jiangxi/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




SD001/2013
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSACR




2013/05/03 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




525338528
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGR49495
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
246



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKMTVDLGQCGL




Shanghai/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




S1358/2013
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




2013/04/03
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




HA 525338689
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIKNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGR49506
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
247



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




Shanghai/S1410/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013 2013/04/03
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




HA 525338708
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGR49554
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
248



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




Zhejiang/SD033/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013 2013/04/11
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




HA 525338789
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVRRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGR49566
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
249



A/duck/Anhui/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




SC702/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/04/16 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




525338809
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDNRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGR49722
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
250



A/homing
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




pigeon/Jiangsu/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




SD184/2013
NEEALRQILRESGGIDKEAMGFTYSEIRTNGATSACR




2013/04/20 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




525339071
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGR49734
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
251



A/pigeon/Shanghai/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




S1069/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/04/02 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




525339091
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTITFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGR49770
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
252



A/wild
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




pigeon/Jiangsu/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




SD001/2013
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




2013/04/17 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




525339151
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGY41893
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
253



A/Huizhou/01/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




2013 2013/08/08
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




HA 552049496
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR





RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDADCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGY42258
FALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEV
254



A/mallard/
VNATETVERTNVPRICSRGKRTVDLGQCGLLGTIXGP




Sweden/91/2002
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQ




2002/12/12 HA
ILRESGGIDKETMGFTYSGIRTNGAXSACRRSGSSFY




552052155
AEMKWLLSNTDNAAFPQMTKSYKNTRNDPALIIWGIH





HSGSTTEQTKLYGSGNKLITVGSSNYQQSFVPSPGAR





PQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRA





SFLRGKSMGIQSGVQIDANCEGDCYHSGGTIISNLPF





QNINSRAVGKCPRYVKQESLLLATGMKNVPEIPKGRG





LFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTAADY





KSTQSAIDQITGKLNRLIEKTNQQFELIDNEFTEVEK





QIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLAD





SEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCM





ASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVI





LWFSFGASCFILLAIAMGLVFMCVKNGNMRCTICI







AHA11441
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTL
255



A/guinea
TERGIEVVNATETVETANIKKICTQGKRPTDLGQCGL




fowl/Nebraska/
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT




17096/2011
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR




2011/04/10 HA
RSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNPRNKPA




557478572
LIVWGVHHSGSATEQTKLYGSGSKLITVGSSKYQQSF





TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA





FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHKGGT





IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP





ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN





EFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH





KCDDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLS





SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR





CTICI







AHA11452
MNTQILALIACMLVGIKGDKICLGHHAVANGTKVNTL
256



A/turkey/Minnesota/
TERGIEVVNATETVETANIKKICTQGKRPTDLGQCGL




32710/2011
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT




2011/07/12
NEEPLRQILRGSGGIDKESMGFTYSGIRTNGATSTCR




HA 557478591
RSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNPRNKPA





LIVWGVHHSGSATEQTKLYGSGSKLITVGSSKYQQSF





TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA





FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHKGGT





IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP





ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFEMIDN





EFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH





KCDDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLS





SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR





CTICI







AHA11461
MNTQILALIACMLVGIKGDKICLGHHAVANGTKVNTL
257



A/turkey/Minnesota/
TERGIEVVNATETVETANIKKICTQGKRPTDLGQCGL




31900/2011
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT




2011/07/05
NEEPLRQILRGSGGIDKESMGFTYSGIRTNGATSTCR




HA 557478606
RSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNPRNKPA





LIVWGVHHSGSATEQTKLYGSGSKLITVGSSKYQQSF





TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA





FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHKGGT





IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP





ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN





EFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH





KCDDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLS





SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR





CTICI







AHK10585
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
258



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Guangdong/G1/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/05/05 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




587680636
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGG53366
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL
259



A/wild
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL




duck/Korea/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




CSM42-34/2011
NEEALRQILRESGGIDKETMGLTYSGIRTNGATSACR




2011/03/
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRDPA




HA 459252887
LIVWGIHHSGSSTEQTKLYGSGSKLITVGSSNYQQSF





VPSPGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSGGT





IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP





ELPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVRLS





SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR





CTICI







AGG53377
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL
260



A/wild
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL




duck/Korea/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




CSM42-1/2011
NEEALRQILRESGGIDKETMGLTYSGIRTNGATSACR




2011/03/
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRDPA




HA 459252925
LIVWGIHHSGSSTEQTKLYGSGSKLITVGSSNYQQSF





VPSPGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSGGT





IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP





ELPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVRLS





SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR





CT







AGG53399
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL
261



A/wild
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL




duck/Korea/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




MHC39-26/2011
NEEALRQILRESGGIDKETMGFTYSGIRTNGATSACR




2011/03/
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRDPA




HA 459253005
LIVWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSF





VPSPGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSGGT





IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP





EPPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR





CTICI







AGG53432
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL
262



A/wild
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL




duck/Korea/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




MHC35-41/2011
NEEALRQILRESGGIDKETMGFTYSGIRTNGATSACR




2011/03/
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRDPA




HA 459253136
LIVWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSF





VPSPGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSGGT





IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP





EPPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR





CT







AGG53476
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL
263



A/wild
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL




duck/Korea/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




SH19-27/2010
NEEALRQILRESGGIDKETMGFTYSGIRTNGATSACR




2010/12/
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRDPA




HA 459253257
LIVWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSF





VPSPGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSGGT





IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP





ELPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR





CTI







AGG53487
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL
264



A/wild
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL




duck/Korea/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




SH19-50/2010
NEEALRQILRESGGIDKETMGFTYSGIRTNGATSACR




2010/01/
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRDPA




HA 459253278
LIVWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSF





VPSPGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSGGT





IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP





ELPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR





CTICI







AGG53520
QILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER
265



A/wild
GVEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGT




duck/Korea/
ITGPPQCDQLLEFSADLIIERREGTDVCYPGKEVNEE




SH20-27/2008
ALRQILRESGGIEKETMGFTYSGIRTNGATSACRRSG




2008/12/
SSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKDPALII




HA 459253409
WGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS





PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIA





PDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGTIIS





NLPFQNINSRAVGKCPRYVKQESLMLATGMKNVPELP





KGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGT





AADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFT





EVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTI





DLADSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCD





DDCMASIRNNTYDHSKYREEAMQNRIQINPVKLSSGY





KDVILWFSFGASCFILLAIAMGLVFICVKNGNMR







AGL43637
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
266



A/Taiwan/1/2013
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




2013// HA
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




496297389
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR





RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGPSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IINNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGL97639
IACMLVGAKGDKICLGHHAVANGTKVNTLTERGIEVV
267



A/mallard/
NATETVETANIKKLCTQGKRPTDLGQCGLLGTLIGPP




Minnesota/AI09-
QCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQI




3770/2009
LRGSGGIDKESMGFTYSGIRTNGATSACRRSGSSFYA




2009/09/12 HA
EMKWLLSNSDNAAFPQMTKSYRNPRNKPALIIWGVHH




505555371
SGSATEQTKLYGSGNKLITVGSSKYQQSFTPSPGARP





QVNGQSGRIDFHWLLLDPNDTVIFTFNGAFIAPDRAS





FFRGESLGVQSDVPLDSGCEGDCFHSGGTIVSSLPFQ





NINPRTVGKCPRYVKQTSLLLATGMRNVPENPKTRGL





FGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTAADYK





STQSAIDQITGKLNRLIDKTNQQFELIDNEFSEIEQQ





IGNVINWTRDSMTELWSYNAELLVAMENQHTIDLADS





EMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCME





SIRNNTYDHTQYRTESLQNRIQIDPVKLS







AGO02477
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
268



A/Xuzhou/1/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




2013 2013/04/25
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




HA 512403688
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR





RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGSKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKSRNMR





CTICI







AGR84942
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
269



A/Suzhou/5/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




2013 2013/04/12
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




HA 526304561
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR





RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGSKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AGR84954
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
270



A/Nanjing/6/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




2013 2013/04/11
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




HA 526304594
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR





RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNRNMR





CTICI







AGR84978
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
271



A/Wuxi/4/2013
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




2013/04/07 HA
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




526304656
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR





RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKSRNMR





CTICI







AGR84990
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
272



A/Wuxi/3/2013
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




2013/04/07 HA
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




526304688
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR





RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKSRNMR





CTICI







AGR85002
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
273



A/Zhenjiang/1/
TERGVEVVNATETVERTNIPRICSKGKMTVDLGQCGL




2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/04/07 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




526304708
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKSRNKR





CTICI







AGR85026
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
274



A/Nanjing/2/
TERGVEVVNATETVERTNIPRICSKGKMTVDLGQCGL




2013 2013/04/05
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




HA 526304762
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR





RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKSRNMR





CTICI







AGU02230
LVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGG
275



A/Zhejiang/
EVVNATETVERTNIPRICSKGKRTVDLGQCGLRGTIT




DTID-ZJU05/2013
GPPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEAL




2013/04/
RQILRESGGIDKEAMGFTYSGIRTNGATSACRRSGSS




HA 532808765
FYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPALIVWG





IHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPG





ARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPD





RASFLRGKSMGIQSGVQVDANCEGDCYHSGGTIISNL





PFQNIDSRAVGKCPRYVKQRSLLLATGMKNVPEIPKG





RGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTAA





DYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFNEV





EKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDL





ADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDD





CMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKD





VILWFSFGASCFILLAIVMGLVFICVKNGNMRCT







AGU02233
FALIAIIPTNADKICLGHHAVSNGTKVNTLTERGGEV
276



A/Zhejiang/
VNATETVERTNFPRICSKGKRTVDLGQCGLRGTITGP




DTID-ZJU08/2013
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQ




2013/04/
ILRESGGIDKEAMGFTYSGIRTNGATSACRRSGSSFY




HA 532808788
AEMKWLLSNTDNAAFPQMTKSYKNTRKSPALIVWGIH





HSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPGAR





PQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRA





SFLRGKSMGIQSGVQVDANCEGDCYHSGGTIISNLPF





QNIDSRAVGKCPRYVKQRSLLLATGMKNVPEIPKGRG





LFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTAADY





KSTQSAIDQITGKLNRLIEKTNQQFELIDNEFNEVEK





QIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLAD





SEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCM





ASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVI





LWFSFGASCFILLAIVMGLVFICVKNGNMRCT







AGW82588
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
277



A/tree
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




sparrow/Shanghai/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




01/2013
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




2013/05/09 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




546235348
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTIGI







AGW82600
ALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV
278



A/Shanghai/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP




CN01/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQI




2013/04/11 HA
LRESGGIDKEAMGFTYSGIRTNGATSACRRSRSSFYA




546235368
EMKWLLSNTDNAAFPQMTKSYKNTRKSPALIVWGIHH





SVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPGARP





QVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRAS





FLRGKSMGIQSGVQVDANCEGDCYHSGGTIMSNLPFQ





NIDSRAVGKCPRYVKQRSLLLATGMKNVPEIPKGRGL





FGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTAADYK





STQSAIDQITGKLNRLIEKTNQQFELIDNEFNEVEKQ





IGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADS





EMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMA





SIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVIL





WFSFGASCFILLAIVMGLVFICVKNGNMRCTICI







AGW82612
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
280



A/Shanghai/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




JS01/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/04/03 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




546235388
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKNPA





LIVWGIHHSGSTAEQTKLYGSGNKLVTVGSSNYQQSF





APSPGARTQVNGQSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDADCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFTEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR





CTICI







AHA11472
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTL
281



A/turkey/
TERGIEVVNATETVETANVKKICTQGKRPTDLGQCGL




Minnesota/31676/
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT




2009 2009/12/08
NEESLRQILRGSGGIDKESMGFTYSGIRTNGETSACR




HA 557478625
RSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNPRDKPA





LIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSF





TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA





FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHSGGT





IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP





EKPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITNKLNRLIDKTNQQFELIDN





EFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH





KCDDQCMESIRNNTYDHTQYRKESLQNRIQIDPVKLS





SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR





CTICI







AHA11483
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTL
282



A/turkey/
TERGIEVVNATETVETANVKKICTQGKRPTDLGQCGL




Minnesota/14135-
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT




2/2009
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR




2009/08/07 HA
RSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNPRDKPA




557478644
LIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSF





TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA





FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHSGGT





IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP





EKPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITSKLNRLIDKTNQQFELIDN





EFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH





KCDDQCMESIRNNTYDHTQYRKESLQNRIQIDPVKLS





SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR





CTICI







AHA11500
TQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTE
283



A/Zhejiang/
RGVEVVNATETVERTNIPRICSKGKRTVDLGQCGLLG




DTID-ZJU10/2013
TITGPPQCDQFLEFSADLIIERREGSDVCYPGKFVNE




2013/10/14 HA
EALRQILRESGGIDKEAMGFTYSGIRTNGATSACRRS




557478676
GSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPALI





VWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVP





SPGARPPVNGLSGRIDFHWLMLNPNDTVTFSFNGAFI





APDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGTII





SNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVPEI





PKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEG





TAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEF





NEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHT





IDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKC





DDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG





YKDVILWFSFGASCFILLAIVMGLVFICVKN







AHA57050
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTL
284



A/turkey/
TERGIEVVNATETVETANVKKICTQGKRPTDLGQCGL




Minnesota/14659/
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT




2009 2009/08/12
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR




HA 558484427
RSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNPRDKPA





LIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSF





TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA





FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHSGGT





IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP





EKPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITSKLNRLIDKTNQQFELIDN





EFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH





NCDDQCMESIRNNTYDHTQYRKESLQNRIQIDPVKLS





SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR





CTICI







AHA57072
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTL
285



A/turkey/
TERGIEVVNATETVETANVKKICTQGKRPTDLGQCGL




Minnesota/18421/
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT




2009 2009/09/09
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR




HA 558484465
RSGSSFYAEMKWLLSNSNDAAFPQMTKSYRNPRDKPA





LIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSF





TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA





FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHSGGT





IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP





EKPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN





EFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH





KCDDQCMESIRNNTYDHTQYRKESLQNRIQIDPVKLS





SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR





CTICI







AHD25003
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
286



A/Guangdong/02/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




2013 2013/10/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




HA 568260567
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR





RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNM







AHF20528
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
287



A/Hong
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




Kong/470129/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013 2013/11/30
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




HA 570933555
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISSLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AHF20568
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
288



A/Shanghai/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




CN02/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/04/02 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




570933626
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IMSNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AHH25185
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
289



A/Guangdong/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




04/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/12/16 HA
NEEALRQILRESGGIEKEAMGFTYSGIRANGATSACR




576106234
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AHJ57411
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
290



A/Shanghai/PD-
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




01/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/01/17 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




585478041
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VSSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCKGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRIIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AHJ57418
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
291



A/Shanghai/PD-
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




02/2014
LGTITGPPQCDQFLEFSADLIIERREGSDICYPGKFV




2014/01/17 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




585478256
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLKGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRIIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AHK10800
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
292



A/Shanghai/01/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/01/03 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




587681014
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRIIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AHM24224
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
293



A/Beijing/3/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




2013 2013/04/16
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




HA 594704802
KEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR





RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AHN96472
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
294



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Shanghai/PD-CN-
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




02/2014
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




2014/01/21 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




602701641
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AHZ39686
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
295



A/Anhui/DEWH72-
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




01/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013// HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




632807036
RSGSSFYAEMKWLLSNTDDAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AHZ39710
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
296



A/Anhui/DEWH72-
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




03/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013// HA
NEEALRQILRESGGIDKEAMGFTYSGIRTDGATSACR




632807076
RSGSSFYAEMKWLLSNTDDAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AHZ39746
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
297



A/Anhui/DEWH72-
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




06/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013// HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




632807136
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGERPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AHZ41929
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL
298



A/mallard/Sweden/
TERGVEVVNATETVERTNVPRICSRGKRTVDLGQCGL




1621/2002
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2002/12/12 HA
NEEALRQILRESGGIDKETMGFTYSGIRTNGATSACR




632810949
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRNDPA





LIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSF





VPSPGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQIDANCEGDCYHSGGT





IISNLPFQNINSRAVGKCPRYVKQESLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIAMGLVFMCVKNGNMR





CTICI







AHZ42537
MNTQILAFIACMLVGAKGDKICLGHHAVANGTKVNTL
299



A/mallard/
TERGIEVVNATETVETANIKKLCTQGKRPTDLGQCGL




Minnesota/AI09-
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT




3770/2009
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR




2009/09/12 HA
RSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPA




632811964
LIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSF





TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA





FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHSGGT





IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP





ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN





EFSEIEQQIGNVINWTRDSMTELWSYNAELLVAMENQ





HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH





KCDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLS





SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR





CTICI







AHZ42549
MNTQILAFIACMLVGVRGDKICLGHHAVANGTKVNTL
300



A/ruddy
TEKGIEVVNATETVESANIKKICTQGKRPTDLGQCGL




turnstone/
LGTLIGPPQCDQFLEFDSDLIIERREGTDVCYPGKFT




Delaware/AI00-
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR




1538/2000
RLGSSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKP




2000/05/20 HA
ALIIWGVHHSGSANEQTKLYGSGNKLITVGSSKYQQS




632811984
FTPSPGARPQVNGQSGRIDFHWLLLDPNDTVIFTENG





AFIAPDRASFFRGESLGIQSDVPLDSSCGGDCFHSGG





TIVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNV





PENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQ





GEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELMD





NEFNEIEQQIGNVINWTRDSMTEVWSYNAELLVAMEN





QHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIF





HKCDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKL





SSGYKDIILWFSFGASCFLLLAIAMGLIFICIKNGNM





RCTICI







AID70634
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
301



A/Shanghai/Mix1/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/01/03 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




660304650
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRIIEKTNQQFELIDN





EFNEVEKQISNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AIN76383
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTL
302



A/Zhejiang/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




LS01/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/08 HA
NEEALRQILRESGGIDKEAMGFTYSGIRINGITSACR




684694637
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AIU46619
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
303



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




Zhejiang/DTID-
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




ZJU06/2013
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




2013/12/ HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




699978931
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVEVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AIU47013
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
304



A/chicken/Suzhou/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




040201H/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/04/
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




HA 699979673
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDMILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ90490
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
305



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Shenzhen/742/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/12/10 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




755178094
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ90526
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
306



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Shenzhen/898/2013
LGTITGPPQCDQFLEFSADLIIERREGSDICYPGKFV




2013/12/09 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACK




755178154
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISSLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





RGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ90538
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
307



A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




chicken/Shenzhen/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




918/2013
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




2013/12/09 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




755178174
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ90576
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
308



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Shenzhen/1665/2013
LGTITGPPQCDQFLEFSADLIIERREGSDICYPGKFV




2013/12/12 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACK




755178238
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





RGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ90588
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
309



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Shenzhen/2110/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/12/13 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




755178258
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSIGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ90661
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
310



A/chicken/Dongguan/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




2912/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/12/18 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




755178380
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ90673
MNTQILVFALTAIIPTNADKICLGHHAVSNGTKVNTL
311



A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




chicken/Dongguan/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




3049/2013
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




2013/12/18 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




755178400
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ90795
MNTQILVFALIAIIPTNADKICLGHHAVPNGTKVNTL
312



A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




chicken/Dongguan/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




3281/2013
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




2013/12/18 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




755178604
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ90891
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
313



A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




chicken/Dongguan/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




3520/2013
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




2013/12/19 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKXPA




755178764
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ90951
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
314



A/chicken/Dongguan/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




3544/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/12/19 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




755178864
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYRNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ91035
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
315



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Shenzhen/3780/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/12/19 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




755179004
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDNRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ91155
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
316



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/4037/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/12/19 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




755179204
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ92005
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
317



A/chicken/Shenzhen/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




801/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/12/09 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




755180629
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





RGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ94254
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
318



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/1374/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/21 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755184382
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPERASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFKHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ94606
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
319



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/191/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/20 HA
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSACR




755184968
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDADCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ96552
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
320



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTIDLGQCGL




Jiangxi/12206/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/03/16 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755188219
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHNKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ96684
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKINTL
321



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Jiangxi/13207/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/03/30 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755188439
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ96732
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
322



A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




13223/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/03/30 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755188519
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJK00354
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL
323



A/duck/Zhejiang/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




LS02/2014
LGTITGPPQCDQFLEFSADLIVERREGSDVCYPGKFV




2014/01/12 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755194469
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKDPA





LIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSF





VPSPGARPLVNGQSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNINSRAVGKCPRYVKQESLLLATGMKNVP





EVPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQVIGKLNRLIEKTNQQFELIDH





EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ





HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFH





KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ91264
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
324



A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




chicken/Dongguan/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




4129/2013
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




2013/12/19 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




755179386
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLMEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ91314
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
325



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




Shaoxing/2417/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/10/20 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755179470
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPPVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ91402
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
326



A/chicken/Huzhou/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




4045/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/10/24 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755179618
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKEVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ91476
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
327



A/chicken/Huzhou/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




4076/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/10/24 HA
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSACR




755179743
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSRGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ91725
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
328



A/chicken/Shaoxing/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




5201/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/10/28 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755180161
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ91885
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
329



A/Shenzhen/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




SP4/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/01/16 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGVISACR




755180429
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





RGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ91909
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
330



A/Shenzhen/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




SP26/2014
LGTITGPPQCDQFLEFSADLIIERREGSDICYPGKFV




2014/01/20 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACK




755180469
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISSLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDGCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





RGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ91945
MNTQILAFALIAIIPTNADKICLGHHAVSNGTKVNTL
331



A/Shenzhen/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




SP38/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/01/22 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




755180529
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIGGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ91957
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
332



A/Shenzhen/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




SP44/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/01/23 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGTTSACR




755180549
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISSLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ91969
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
333



A/Shenzhen/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




SP48/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/01/23 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755180569
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ91993
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
334



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/4119/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/12/19 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




755180609
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLLGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFTLLAIVMGLVFICVKNGNMR





CTICI







AJJ92031
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
335



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/4064/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2013/12/19 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




755180672
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVESSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ92967
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTL
336



A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




chicken/Jiangxi/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




9469/2014
NEEALRQILRESGGIDKEAMGFTYSGIRINGVISACR




2014/02/16 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




755182232
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ93027
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTL
337



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Jiangxi/9558/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/16 HA
KEEALRQILRESGGIDKEAMGFTYSGIRINGVISACR




755182332
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ93051
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTL
338



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Jiangxi/10573/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/18 HA
NEEALRQILRESGGIDKEAMGFTYSGIRINGVISACR




755182372
RSGSSFYAEMKWLLSNTDDAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ93845
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
339



A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




chicken/Dongguan/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




157/2014
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




2014/02/20 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




755183695
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ93857
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
340



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/169/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/20 HA
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSACM




755183715
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDADCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ93869
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
341



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/173/2014
LGTVTGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/20 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




755183735
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ93881
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
342



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/189/2014
LGTVTGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/20 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




755183755
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPKYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ93907
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
343



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/449/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/20 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




755183799
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPERASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ93931
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
344



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/536/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/20 HA
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSACR




755183839
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDADCEGDCYHSGGT





IISKLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ93943
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
345



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/568/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/20 HA
NEEALRQILRESGGIEKEAMGFTYSGIRANGATSACR




755183859
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





GGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ93979
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
346



A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




chicken/Dongguan/
LGTVTGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




656/2014
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




2014/02/20 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




755183919
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFGLIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ94134
MNTQILVLALIAIIPTNADKICLGHHAVSNGTKVNTL
347



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/1051/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/21 HA
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSACR




755184182
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDADCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVXLS





XGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ94158
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
348



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/1075/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/21 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755184222
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPERASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFKHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYRGEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ94182
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
349



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/1177/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/21 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACK




755184262
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSIAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ94194
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
350



A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTIDLGQCGL




chicken/Dongguan/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




1264/2014
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




2014/02/21 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




755184282
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPERASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFKHQNAQG





EGTAADYKSTQSAIDQVIGKLNRLIEKTNQQFELIDN





EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYRGEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFMLLAIVMGLVFICVKNGNMR





CTICI







AJJ94206
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
351



A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




chicken/Dongguan/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




1268/2014
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




2014/02/21 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




755184302
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPERASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISDLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ94344
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
352



A/silkie
TERGVEVVNSTETVERTNIPRICSKGKKTVDLGQCGL




chicken/Dongguan/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




1451/2014
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSACR




2014/02/21 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




755184532
IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDADCEGDCYHSGGT





IISNLPFQNIDSRTVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ94356
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
353



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/1456/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/21 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755184552
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPERASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ94396
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
354



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/1494/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/21 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




755184618
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





ETPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ94754
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
355



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/748/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/20 HA
NEEALRQILRESGGIEKEAMGFTYSGIRANGATSACR




755185215
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSNAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





GGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ94838
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
356



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/835/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/20 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




755185356
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSASTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFGFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ94862
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
357



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/843/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/20 HA
NEEALRQILRESGGIEKEAMGFTYSGIRTNGATSACR




755185396
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





GGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ94886
MNTQILAFALIAIIPTNADKICLGHHAVSNGTKVNTL
358



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/851/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/20 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




755185436
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ94910
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
359



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/874/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/20 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




755185476
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSASTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ94959
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
360



A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




chicken/Dongguan/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




967/2014
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACX




2014/02/21 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




755185558
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ95048
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
361



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




Dongguan/1009/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/21 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




755185708
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





ETPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ95171
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
362



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/1314/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/21 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755185913
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVIFNFNGA





FIAPERASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFKHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ95227
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
363



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/1382/2014
LGTITGPPQCDQFLEFSADLIIERREGSDICYPGKFV




2014/02/21 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




755186006
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPERASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ95251
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
364



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/1401/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/21 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755186046
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYKRVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ95346
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
365



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/1548/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/21 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755186206
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYKRVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHNKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ95382
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
366



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Dongguan/1690/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/21 HA
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSACR




755186266
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSIGIQSGVQVDADCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ95464
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
367



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




Shenzhen/138/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/19 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755186404
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPERASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFKHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYRGEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFMLLAIVMGLVFICVKNGNMR





CTICI







AJJ95572
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
368



A/chicken/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




Dongguan/1100/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/21 HA
NEEALRQILRESGGIEKEAMGFTYSGIRANGATSACR




755186584
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





GGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ95584
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
369



A/silkie
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




chicken/Dongguan/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




1519/2014
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




2014/02/21 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




755186604
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPERASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFKHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYRGEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFMLLAIVMGLVFICVKNGNMR





CTICI







AJJ95596
MNTQILAFALIAIIPTNADKICLGHHAVSNGTKVNTL
370



A/Shenzhen/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




SP58/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/01/25 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR




755186624
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ95620
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
371



A/Shenzhen/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




SP75/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/15 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGSTSACR




755186664
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAVVMGLVFICVKNGNMR





CTICI







AJJ95632
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
372



A/Shenzhen/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




SP62/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/05 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755186684
RSGSSFYAEMKWLLSNTDNATFPQMTKSYKNTRKSPA





LIIWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ96720
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
373



A/chicken/
TERGVEVVNATETVERTTIPRICSKGKKTVDLGQCGL




Jiangxi/13220/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/03/30 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755188499
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSRGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ96817
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTL
374



A/chicken/
TERGVEVVNATEIVERTNIPRICSKGKKTVDLGQCGL




Jiangxi/9513/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/02/16 HA
NEEALRQILRESGGIDKEAMGFTYSGIRINGVISACR




755188661
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ96841
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
375



A/Shenzhen/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




SP139/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/04/02 HA
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSTCR




755188701
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRACFLRGKSMGIQSGVQVDADCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVERQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ96889
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
376



A/chicken/Jiangxi/
TERGVEVVNATETVERTXIPRICSKGKKTVDLGQCGL




13496/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/04/11 HA
NEEALRQILRESGGIDKXAMGFTYSGIRTNGATSACR




755188781
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSXGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ96901
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
377



A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




13502/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/04/11 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755188801
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSXGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ96925
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
378



A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




13513/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/04/11 HA
NEEALRQILRESGGIDKEAMGFTYNGIRTNGATSACR




755188841
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





IIVWGIHHTVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDLHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIAKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ97267
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
379



A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




13252/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/03/30 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755189411
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ97291
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
380



A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




13493/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/04/06 HA
NEEALRQILRESGGIDKEAMGFTYNGIRTNGATSACR




755189451
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIAKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ97331
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
381



A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




13512/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/04/06 HA
NEEALRQILRESGGIDKEAMGFTYNGIRTNGATSACR




755189517
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSIGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIAKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ97373
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
382



A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




13521/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/04/06 HA
NEEALRQILRESGGIDKEAMGFTYNGIRTNGATSACR




755189587
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPXRASFLRGKSXGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIAKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ97443
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
383



A/chicken/Jiangxi/
TERGVEVVNATETVERTTIPRICSKGKRTVDLGQCGL




13530/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/04/06 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755189702
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSRGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ97582
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
384



A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




14023/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/04/13 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755189933
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIAKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ97697
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
385



A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




14517/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/04/20 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755190125
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCDGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ97709
MNTQILVFALIAIIPANADKICLGHHAVSNGTKVNTL
386



A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




14518/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/04/20 HA
NEEALRQILRESGGIDKEAMGFTYNGIRTNGATSACR




755190145
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGNCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIAKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ97745
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
387



A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




14554/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/04/20 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755190205
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELMDN





EFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ97757
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
388



A/chicken/Shantou/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




2537/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/04/16 HA
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSACR




755190225
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDADCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFKHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ97841
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
389



A/duck/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




15044/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/04/27 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755190365
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIAKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVRLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ97899
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
390



A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL




15524/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/05/05 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755190462
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIAKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFMCVKNGNMR





CTICI







AJJ97925
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL
391



A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




chicken/Shantou/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2050/2014
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSACR




2014/03/25 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA




755190506
IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDADCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EVPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ97973
MNTQILVFALISIIPTNADKICLGHHAVSNGTKVNTL
392



A/chicken/Shantou/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




4325/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/07/01 HA
NEEALRQILRKSGGIDKEAMGFTYSGIRINGVISACR




755190586
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDADCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP





EVPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI







AJJ97998
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTL
393



A/chicken/Shantou/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL




4816/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV




2014/07/22 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR




755190628
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA





LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF





VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA





FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT





IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP





EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG





EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELVDN





EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ





HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH





KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS





SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR





CTICI
















TABLE 16







Exemplary Influenza HA Stem Antigens













SEQ ID

SEQ ID


Strain
Foldon version
NO:
AA seq
NO:





H1N1
DTVDTVLEKNVTVTHSVNL
394

METPAQLLFLLLLWLPDTTGDT

403


A/Puerto
LEDSHGSANSSLPYQNTHP

VDTVLEKNVTVTHSVNLLEDSH



Rico/8/
TTNGESPKYVRSAKLRMVT

GSANSSLPYQNTHPTTNGESPK



1934
GLRNGSAGSATQNAINGIT

YVRSAKLRMVTGLRNGSAGSAT




NKVNTVIEKMNIQDTATGK

QNAINGITNKVNTVIEKMNIQD




EFNKDEKRMENLNKKVDDG

TATGKEFNKDEKRMENLNKKVD




FLDIWTYNAELLVLLENER

DGFLDIWTYNAELLVLLENERT




TLDAHDSQGTgggyipeap

LDAHDSQGTGGGYIPEAPRDGQ




rdgqayvrkdgewvllstf


AYVRKDGEWVLLSTFL





l








H1N1
DTVDTVLEKNVTVTHSVNL
395

METPAQLLFLLLLWLPDTTGDT

404


A/VietNam/
LEDKHGSANTSLPFQNTHP

VDTVLEKNVTVTHSVNLLEDKH



850/2009
TTNGKCPKYVKSTKLRLAT

GSANTSLPFQNTHPTTNGKCPK




GLRNGSAGSATQNAIDEIT

YVKSTKLRLATGLRNGSAGSAT




NKVNSVIEKMNTQDTATGK

QNAIDEITNKVNSVIEKMNTQD




EFNHDEKRIENLNKKVDDG

TATGKEFNHDEKRIENLNKKVD




FLDIWTYNAELLVLLENER

DGFLDIWTYNAELLVLLENERT




TLDAHDSQGTgggyipeap

LDAHDSQGTGGGYIPEAPRDGQ




rdgqayvrkdgewvllstf


AYVRKDGEWVLLSTFL





l








H1N1
DTVDTVLEKNVTVTHSVNL
396

METPAQLLFLLLLWLPDTTGDT

405


A/New
LEDSHGSANSSLPFQNTHP

VDTVLEKNVTVTHSVNLLEDSH



Caledonia/
TTNGESPKYVRSAKLRMVT

GSANSSLPFQNTHPTTNGESPK



20/99
GLRNGSAGSATQNAINGIT

YVRSAKLRMVTGLRNGSAGSAT




NKVNSVIEKMNTQDTAVGK

QNAINGITNKVNSVIEKMNTQD




EFNKDERRMENLNKKVDDG

TAVGKEFNKDERRMENLNKKVD




FLDIWTYNAELLVLLENER

DGFLDIWTYNAELLVLLENERT




TLDAHDSQGTgggyipeap

LDAHDSQGTGGGYIPEAPRDGQ




rdgqayvrkdgewvllstf


AYVRKDGEWVLLSTFL





l








H1N1
DTVDTVLEKNVTVTHSVNL
397

METPAQLLFLLLLWLPDTTGDT

406


A/
LEDKHGSANTSLPFQNTHP

VDTVLEKNVTVTHSVNLLEDKH



California/
TTNGKSPKYVKSTKLRLAT

GSANTSLPFQNTHPTTNGKSPK



04/2009
GLRNGSAGSATQNAIDEIT

YVKSTKLRLATGLRNGSAGSAT




NKVNSVIEKMNTQDTAVGK

QNAIDEITNKVNSVIEKMNTQD




EFNHDEKRIENLNKKVDDG

TAVGKEFNHDEKRIENLNKKVD




FLDIWTYNAELLVLLENER

DGFLDIWTYNAELLVLLENERT




TLDAHDSQGTgggyipeap

LDAHDSQGTGGGYIPEAPRDGQ




rdgqayvrkdgewvllstf


AYVRKDGEWVLLSTFL





l








H3N2
HAVPNGTIVKTITNDQIEV
398

METPAQLLFLLLLWLPDTTGHA

407


A/
TNATEgsaPNDKPFQNtNR

VPNGTIVKTITNDQIEVTNATE



Wisconsin/
tTtGACPRYVKQNTLKLAT

GSAPNDKPFQNTNRTTTGACPR



67/2005
GMRNgsagsaTQAAINQIN

YVKQNTLKLATGMRNGSAGSAT




GKLNRLIGKTNEKdHQdEK

QAAINQINGKLNRLIGKTNEKD




EFSEdEGRIQDLEKYVEDT

HQDEKEFSEDEGRIQDLEKYVE




KIDLWSYNAELLVALENQH

DTKIDLWSYNAELLVALENQHT




TIDaTDSQGTgggyipeap

IDATDSQGTGGGYIPEAPRDGQ




rdgqayvrkdgewvllstf


AYVRKDGEWVLLSTFL





l








H5N1
EQVDTIMEKNVTVTHAQDI
399

METPAQLLFLLLLWLPDTTGEQ

408


A/Vietnam/
LEKTHGSANSSMPFHNTHP

VDTIMEKNVTVTHAQDILEKTH



1203/2004
NTTGESPKYVKSNRLVLAT

GSANSSMPFHNTHPNTTGESPK




GLRNGSAGSATQKAIDGVT

YVKSNRLVLATGLRNGSAGSAT




NKVNSIIDKMNTQFEADGR

QKAIDGVTNKVNSIIDKMNTQF




EFNNDERRIENLNKKMEDG

EADGREFNNDERRIENLNKKME




FLDVWTYNAELLVLMENER

DGFLDVWTYNAELLVLMENERT




TLDAHDSQGTgggyipeap

LDAHDSQGTGGGYIPEAPRDGQ




rdgqayvrkdgewvllstf


AYVRKDGEWVLLSTFL





l








H7N9
TKVNTLTERGVEVVNATET
400

METPAQLLFLLLLWLPDTTGTK

409


(A/Anhui/
VERTgsaISNLPFQNtDSt

VNTLTERGVEVVNATETVERTG



1/2013)
AnGKCPRYVKQRSLLLATG

SAISNLPFQNTDSTANGKCPRY




MKNgsagsaTQSAIDQITG

VKQRSLLLATGMKNGSAGSATQ




KLNRLIEKTNQQdELtDNE

SAIDQITGKLNRLIEKTNQQDE




FNEdEKQIGNVINWTRDSI

LTDNEFNEDEKQIGNVINWTRD




TEVWSYNAELLVAMENQHT

SITEVWSYNAELLVAMENQHTI




IDaADSQGTgggyipeapr

DAADSQGTGGGYIPEAPRDGQA




dgqayvrkdgewvllstfl


YVRKDGEWVLLSTFL







H9N2
ETVDTLTETNVPVTHAKEL
401

METPAQLLFLLLLWLPDTTGET

410


A/Hong
LHTEHgsaNSTLPFHNtSK

VDTLTETNVPVTHAKELLHTEH



Kong/1073/
tAnGTCPKYVRVNSLKLAV

GSANSTLPFHNTSKTANGTCPK



99
GLRNgsagsaTQKAIDKIT

YVRVNSLKLAVGLRNGSAGSAT




SKVNNIVDKMNKQdEItDH

QKAIDKITSKVNNIVDKMNKQD




EFSEdETRLNMINNKIDDQ

EITDHEFSEDETRLNMINNKID




IQDVWAYNAELLVLLENQK

DQIQDVWAYNAELLVLLENQKT




TLDaHDSQGTgggyipeap

LDAHDSQGTGGGYIPEAPRDGQ




rdgqayvrkdgewvllstf


AYVRKDGEWVLLSTFL





l








H10N8
TIVKTLTNEQEEVTNATET
402

METPAQLLFLLLLWLPDTTGTI

411


A/JX346/
VESTGgsaNTRLPFQNtSP

VKTLTNEQEEVTNATETVESTG



2013
tTnGQCPKYVNRRSLMLAT

GSANTRLPFQNTSPTTNGQCPK




GMRNgsagsaTQAAIDQIT

YVNRRSLMLATGMRNGSAGSAT




GKLNRLVEKTNTEdSItSE

QAAIDQITGKLNRLVEKTNTED




FSEIEHQIGNVINWTKDSI

SITSEFSEIEHQIGNVINWTKD




TDIWTYQAELLVAMENQHT

SITDIWTYQAELLVAMENQHTI




IDaADSQGTgggyipeapr

DAADSQGTGGGYIPEAPRDGQA




dgqayvrkdgewvllstfl


YVRKDGEWVLLSTFL







H3N2



METPAQLLFLLLLWLPDTTGAS

412


A/Hong


PNGTLVKTITDDQIEVTNATEL



Kong/1/


VQSSGSAGSANDKPFQNTNKRT



1968 stem


SGASPKYVKQNTLKLATGQRGS



RNA


AGSAATDQINGKLNRVIEKTNE






KDHQIEKEFSEDEGRIQDLEKY






VEDTKIDLWSYNAELLVALENQ






HTIDLTDSQGTGGGYIPEAPRD







GQAYVRKDGEWVLLSTFL











The first underlined sequence for each of the amino acid sequences listed in Table 16, indicates a signal or secretory sequence, which may be substituted by an alternative sequence that achieves the same or similar function, or the signal or secretory sequence may be deleted. The second underlined sequence for the amino acid sequences listed in Table 16, indicates a foldon sequence, which is a heterologous sequence that naturally trimerizes, to bring 3 HA stems together in a trimer. Such foldon sequence may be substituted by an alternative sequence, which achieves the same or similar function.









TABLE 17







Exemplary Influenza Constructs









Construct

SEQ


Description
ORF
ID NO:





Influenza

METPAQLLFLLLLWLPDTTGGLFGAIAGFIENGWEGMIDGWYGFRH

413


H3HA6
QNSEGTGQAADLKSTQAAIDQINGKLNRVIEKTNEKDHQIEKEFSE




DEGRIQDLEKYVEDTKIDLWSYNAELLVALENQHTIDLTDSEMNKL




FEKTRRQLRENAEEMGNGCFKIYHKCDNACIESIRNGTYDHDVYRD




EALNNRFQGSAGSAGDNSTATLCLGHHAVPNGTLVKTITDDQIEVT




NATELVQSSGSAGSANDKPFQNTNKETTGATPKYVKQNTLKLATGM




R






Influenza

METPAQLLFLLLLWLPDTTGGLFGAIAGFIEGGWTGMIDGWYGYHH

414


H1HA6
QNEQGSGYAADQKSTQNAINGITNKVNTVIEKMNIQDTATGKEFNK




DEKRMENLNKKVDDGFLDIWTYNAELLVLLENERTLDFHDSNVKNL




YEKVKSQLKNNAKEIGNGCFEFYHKCDNECMESVRNGTYDYPKYSE




ESKLNREKGSAGSAAADADTICIGYHANNSTDTVDTVLEKNVTVTH




SVNLLEDSHGSANSSLPYQNTHPTTNGESPKYVRSAKLRMVTGLRN




IP






Influenza

METPAQLLFLLLLWLPDTTGDTVDTVLEKNVTVTHSVNLLEDSHGS

415


H1HA10-
ANSSLPYQNTHPTTNGESPKYVRSAKLRMVTGLRNGGAGSATQNAI



Foldon_ΔNgly1
NGITNKVNTVIEKMNIQDTATGKEFNKDEKRMENLNKKVDDGFLDI




WTYNAELLVLLENERTLDAHDSQGTGGGYIPEAPRDGQAYVRKDGE




WVLLSTFL






Influenza

METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDTVDTVLEKNVTV

416


eH1HA
THSVNLLEDSHNGKLCRLKGIAPLQLGKCNIAGWLLGNPECDPLLP




VRSWSYIVETPNSENGICYPGDFIDYEELREQLSSVSSFERFEIFP




KESSWPNHNTNGVTAACSHEGKSSFYRNLLWLTEKEGSYPNLKNSY




VNKKGKEVLVLWGIHHPSNSKEQQNLYQNENAYVSVVTSNYNRRFT




PEIAERPKVRDQAGRMNYYWTLLKPGDTIIFEANGNLIAPMYAFAL




SRGFGSGIITSNASMHECNTKCQTPLGAINSSLPYQNIHPVTIGEC




PKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGFIEGGWTGMIDGWY




GYHHQNEQGSGYAADQKSTQNAINGITNKVNTVIEKMNIQFTAVGK




EFNKLEKRMENLNKKVDDGFLDIWTYNAELLVLLENERTLDFHDSN




VKNLYEKVKSQLKNNAKEIGNGCFEFYHKCDNECMESVRNGTYDYP




KYSEESKLNREKVDGVKLESMGIGSAGSAGYIPEAPRDGQAYVRKD




GEWVLLSTFL






Influenza
MKANLLVLLCALAAADADTICIGYHANNSTDTVDTVLEKNVTVTHS
417


eH1HA_Native
VNLLEDSHNGKLCRLKGIAPLQLGKCNIAGWLLGNPECDPLLPVRS



SS
WSYIVETPNSENGICYPGDFIDYEELREQLSSVSSFERFEIFPKES




SWPNHNTNGVTAACSHEGKSSFYRNLLWLTEKEGSYPNLKNSYVNK




KGKEVLVLWGIHHPSNSKEQQNLYQNENAYVSVVTSNYNRRFTPEI




AERPKVRDQAGRMNYYWTLLKPGDTIIFEANGNLIAPMYAFALSRG




FGSGIITSNASMHECNTKCQTPLGAINSSLPYQNIHPVTIGECPKY




VRSAKLRMVTGLRNIPSIQSRGLFGAIAGFIEGGWTGMIDGWYGYH




HQNEQGSGYAADQKSTQNAINGITNKVNTVIEKMNIQFTAVGKEFN




KLEKRMENLNKKVDDGFLDIWTYNAELLVLLENERTLDFHDSNVKN




LYEKVKSQLKNNAKEIGNGCFEFYHKCDNECMESVRNGTYDYPKYS




EESKLNREKVDGVKLESMGIGSAGSAGYIPEAPRDGQAYVRKDGEW




VLLSTFL






H1HA10TM-

METPAQLLFLLLLWLPDTTGDTVDTVLEKNVTVTHSVNLLEDSHGS

418


PR8 (H1
ANSSLPYQNTHPTTNGESPKYVRSAKLRMVTGLRNGSAGSATQNAI



A/Puerto
NGITNKVNTVIEKMNIQDTATGKEFNKDEKRMENLNKKVDDGFLDI



Rico/8/34 HA),
WTYNAELLVLLENERTLDAHDSQGTGGILAIYSTVASSLVLLVSLG



with TM
AISFWMCSNGSLQCRICI



domain, without




foldon (with




IgG Kappa




leader)







H1HA10-PR8-

METPAQLLFLLLLWLPDTTGDTVDTVCEKNVTVTHSVNLLEDSHGS

419


DS (H1
ANSSLPYQNTHPTTNGESPKYVRSAKLRMVTGLRNGSAGSATQNAI



A/Puerto
NCITNKVNTVIEKMNIQDTATGKEFNKDEKRMENLNKKVDDGFLDI



Rico/8/34 HA),
WTYNAELLVLLENERTLDAHDS



ds bond,




without foldon




(with IgG




Kappa leader)







pH1HA10-

METPAQLLFLLLLWLPDTTGDTVDTVCEKNVTVTHSVNLLEDKHGS

420


Cal04-DS (H1
ANTSLPFQNTHPTTNGKSPKYVKSTKLRLATGLRNGSAGSATQNAI



A/California/04/
DCITNKVNSVIEKMNTQDTAVGKEFNHDEKRIENLNKKVDDGFLDI



2009 HA), ds
WTYNAELLVLLENERTLDAHDS



bond, without




foldon (with




IgG Kappa




leader)







Nucleoprotein
MASQGTKRSYEQMETDGERQNATEIRASVGKMIDGIGRFYIQMCTE
421


from H3N2 (no
LKLSDYEGRLIQNSLTIERMVLSAFDERRNRYLEEHPSAGKDPKKT



IgG Kappa
GGPIYKRVDGRWMRELVLYDKEEIRRIWRQANNGDDATAGLTHMMI



leader)
WHSNLNDTTYQRTRALVRTGMDPRMCSLMQGSTLPRRSGAAGAAVK




GIGTMVMELIRMIKRGINDRNFWRGENGRKTRSAYERMCNILKGKF




QTAAQRAMMDQVRESRNPGNAEIEDLIFSARSALILRGSVAHKSCL




PACVYGPAVSSGYNFEKEGYSLVGIDPFKLLQNSQVYSLIRPNENP




AHKSQLVWMACHSAAFEDLRLLSFIRGTKVSPRGKLSTRGVQIASN




ENMDNMESSTLELRSRYWAIRTRSGGNTNQQRASAGQISVQPTFSV




QRNLPFEKSTVMAAFTGNTEGRTSDMRAEIIRMMEGAKPEEVSFRG




RGVFELSDEKATNPIVPSFDMSNEGSYFFGDNAEEYDN






HA10 version

METPAQLLFLLLLWLPDTTGHVVKTATQGEVNVTGVIPLTTTPTGS

422


for Influenza B
ANKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYGSAGSATQEAI



strain
NKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADT




ISSQIELAVLLSNEGIINSEDEGTGGGYIPEAPRDGQAYVRKDGEW




VLLSTFL






B/Yamagata/16/
MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIP
423


1988 mHA
LTTTPTKSHFANLKGTKTRGKLCPNCLNCTDLDVALGRPMCMGTIP




SAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYENIRLSTHN




VINAERAPGGPYRLGTSGSCPNVTSRNGFFATMAWAVPRDNKTATN




PLTVEVPYICTKGEDQITVWGFHSDDKTQMKNLYGDSNPQKFTSSA




NGVTTHYVSQIGDFPNQTEDGGLPQSGRIVVDYMVQKPGKTGTIVY




QRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPY




YTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAG




FLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNS




LSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAV




LLSNEGIINSEDEHLLALERKLKKMLGPSAVDIGNGCFETKHKCNQ




TCLDRIAAGTFNAGEFSLPTFDSLNITAASLNDDGLDNHTILLYYS




TAASSLAVTLMIAIFIVYMVSRDNVSCSICL






B/Yamagata/16/
MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIP
424


1988 sHA
LTTTPTKSHFANLKGTKTRGKLCPNCLNCTDLDVALGRPMCMGTIP




SAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYENIRLSTHN




VINAERAPGGPYRLGTSGSCPNVTSRNGFFATMAWAVPRDNKTATN




PLTVEVPYICTKGEDQITVWGFHSDDKTQMKNLYGDSNPQKFTSSA




NGVTTHYVSQIGDFPNQTEDGGLPQSGRIVVDYMVQKPGKTGTIVY




QRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPY




YTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAG




FLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNS




LSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAV




LLSNEGIINSEDEHLLALERKLKKMLGPSAVDIGNGCFETKHKCNQ




TCLDRIAAGTFNAGEFSLPTFDSLNITAASLNDDGLDNHT






B/Victoria/02/
MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIP
425


1987 mHA
LTTTPTKSHFANLKGTKTRGKLCPKCLNCTDLDVALGRPKCTGTIP




SAKASILHEVKPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHN




VINAETAPGGPYKVGTSGSCPNVTNGNGFFATMAWAVPKNDNNKTA




TNPLTVEVPYICTEGEDQITVWGFHSDNEAQMVKLYGDSKPQKFTS




SANGVTTHYVSQIGGFPNQAEDGGLPQSGRIVVDYMVQKSGKTGTI




TYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSK




PYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKEKGFFGAI




AGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNL




NSLSELEVKNLQRLSGAMDELHNKILELDEKVDDLRADTISSQIEL




AVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKC




NQTCLDRIAAGTFNAGEFSLPTFDSLNITAASLNDDGLDNHTILLY




YSTAASSLAVTLMIAIFIVYMVSRDNVSCSICl






B/Victoria/02/
MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIP
426


1987 sHA
LTTTPTKSHFANLKGTKTRGKLCPKCLNCTDLDVALGRPKCTGTIP




SAKASILHEVKPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHN




VINAETAPGGPYKVGTSGSCPNVTNGNGFFATMAWAVPKNDNNKTA




TNPLTVEVPYICTEGEDQITVWGFHSDNEAQMVKLYGDSKPQKFTS




SANGVTTHYVSQIGGFPNQAEDGGLPQSGRIVVDYMVQKSGKTGTI




TYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSK




PYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKEKGFFGAI




AGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNL




NSLSELEVKNLQRLSGAMDELHNKILELDEKVDDLRADTISSQIEL




AVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKC




NQTCLDRIAAGTFNAGEFSLPTFDSLNITAASLNDDGLDNHT






B/Brisbane/60/
MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIP
427


2008 mHA
LTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIP




SARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHN




VINAENAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPKNDKNKTA




TNPLTIEVPYICTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTS




SANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTI




TYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSK




PYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAI




AGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNL




NSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIEL




AVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKC




NQTCLDRIAAGTFDAGEFSLPTFDSLNITAASLNDDGLDNHTILLY




YSTAASSLAVTLMIAIFVVYMVSRDNVSCSICL






B/Brisbane/60/
MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIP
428


2008 sHA
LTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIP




SARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHN




VINAENAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPKNDKNKTA




TNPLTIEVPYICTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTS




SANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTI




TYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSK




PYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAI




AGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNL




NSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIEL




AVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKC




NQTCLDRIAAGTFDAGEFSLPTFDSLNITAASLNDDGLDNHT






B/Phuket/3073/
MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIP
429


2013 mHA
LTTTPTKSYFANLKGTRTRGKLCPDCLNCTDLDVALGRPMCVGTTP




SAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEKIRLSTQN




VIDAEKAPGGPYRLGTSGSCPNATSKIGFFATMAWAVPKDNYKNAT




NPLTVEVPYICTEGEDQITVWGFHSDNKTQMKSLYGDSNPQKFTSS




ANGVTTHYVSQIGDFPDQTEDGGLPQSGRIVVDYMMQKPGKTGTIV




YQRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKP




YYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIA




GFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLN




SLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELA




VLLSNEGIINSEDEHLLALERKLKKMLGPSAVDIGNGCFETKHKCN




QTCLDRIAAGTFDAGEFSLPTFDSLNITAASLNDDGLDNHTILLYY




STAASSLAVTLMLAIFIVYMVSRDNVSCSICL






B/Phuket/3073/
MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIP
430


2013 sHA
LTTTPTKSYFANLKGTRTRGKLCPDCLNCTDLDVALGRPMCVGTTP




SAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEKIRLSTQN




VIDAEKAPGGPYRLGTSGSCPNATSKIGFFATMAWAVPKDNYKNAT




NPLTVEVPYICTEGEDQITVWGFHSDNKTQMKSLYGDSNPQKFTSS




ANGVTTHYVSQIGDFPDQTEDGGLPQSGRIVVDYMMQKPGKTGTIV




YQRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKP




YYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIA




GFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLN




SLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELA




VLLSNEGIINSEDEHLLALERKLKKMLGPSAVDIGNGCFETKHKCN




QTCLDRIAAGTFDAGEFSLPTFDSLNITAASLNDDGLDNHT






Pandemic

METPAQLLFLLLLWLPDTTGDTVDTVLEKNVTVTHSVNLLEDKHGS

431


H1HA10 from
ANTSLPFQNTHPTTNGKSPKYVKSTKLRLATGLRNGSAGSATQNAI



California 04
DEITNKVNSVIEKMNTQDTAVGKEFNHDEKRIENLNKKVDDGFLDI



strain, without
WTYNAELLVLLENERTLDAHDSQGTGGDIIKLLNEQVNKEMQSSNL



foldon and with
YMSMSSWCYTHSLDGAGLFLFDHAAEEYEHAKKLIIFLNENNVPVQ



ferritin fusion
LTSISAPEHKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKDHA



for particle
TFNFLQWYVAEQHEEEVLFKDILDKIELIGNENHGLYLADQYVKGI



formation
AKSRKS






Gen6 HA SS

METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDTVDTVLEKNVTV

432


construct with
THSVNLGSGLRMVTGLRNIPQRETRGLFGAIAGFIEGGWTGMVDGW



ferritin
YGYHHQNEQGSGYAADQKSTQNAINGITNMVNSVIEKMGSGGSGTD




LAELLVLLLNERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGCFEF




YHKCNNECMESVKNGTYDYPKYSEESKLNREKIDSGGDIIKLLNEQ




VNKEMQSSNLYMSMSSWCYTHSLDGAGLFLFDHAAEEYEHAKKLII




FLNENNVPVQLTSISAPEHKFEGLTQIFQKAYEHEQHISESINNIV




DHAIKSKDHATFNFLQWYVAEQHEEEVLFKDILDKIELIGNENHGL




YLADQYVKGIAKSRKS






Gen6 HA SS

METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDTVDTVLEKNVTV

433


construct with
THSVNLGSGLRMVTGLRNIPQRETRGLFGAIAGFIEGGWTGMVDGW



foldon
YGYHHQNEQGSGYAADQKSTQNAINGITNMVNSVIEKMGSGGSGTD




LAELLVLLLNERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGCFEF




YHKCNNECMESVKNGTYDYPKYSEESKLNREKIDPGSGYIPEAPRD




GQAYVRKDGEWVLLSTFL






#4900 construct

METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDTVDTVLEKNVTV

434


without
THSVNLLENGGGGKYVCSAKLRMVTGLRNKPSKQSQGLFGAIAGFT



cleavage site
EGGWTGMVDGWYGYHHQNEQGSGYAADQKSTQNAINGITNKVNSVI



and tag
EKMNTQYTAIGCEYNKSERCMKQIEDKIEEIESKIWCYNAELLVLL




ENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGCFEFYHKCNDEC




MESVKNGTYDYPKYSEESKLNREKIDGVKLESMGVYQ






Pandemic

METPAQLLFLLLLWLPDTTGDTVDTVLEKNVTVTHSVNLLEDKHGS

435


H1HA10 from
ANTSLPFQNTHPTTNGKSPKYVKSTKLRLATGLRNGSAGSATQNAI



California 04
DEITNKVNSVIEKMNTQDTAVGKEFNHDEKRIENLNKKVDDGFLDI



strain, without
WTDLAELLVLLENERTLDAHDS



foldon and with




Y94D/N95L




mutation for




trimerization







Pandemic

METPAQLLFLLLLWLPDTTGDTVDTVLEKNVTVTHSVNLLEDKHGS

436


H1HA10 from
ANTSLPFQNTHPTTNGKSPKYVKSTKLRLATGLRNGSAGSATQNAI



California 04
DEITNKVNSVIEKMNTQDTAVGCEFNHDEKCIENLNKKVDDGFLDI



strain, without
WTYNAELLVLLENERTLDAHDS



foldon and with




K68C/R76C




mutation for




trimerization







H1HA10 from

METPAQLLFLLLLWLPDTTGDTVDTVLEKNVTVTHSVNLLEDSHGS

437


A/Puerto
ANSSLPYQNTHPTTNGESPKYVRSAKLRMVTGLRNGSAGSATQNAI



Rico/8/34
NGITNKVNTVIEKMNIQDTATGKEFNKDEKRMENLNKKVDDGFLDI



strain, without
WTDLAELLVLLENERTLDAHDS



foldon and with




Y94D/N95L




mutation for




trimerization







H1HA10 from

METPAQLLFLLLLWLPDTTGDTVDTVLEKNVTVTHSVNLLEDSHGS

438


A/Puerto
ANSSLPYQNTHPTTNGESPKYVRSAKLRMVTGLRNGSAGSATQNAI



Rico/8/34
NGITNKVNTVIEKMNIQDTATGCEFNKDEKCMENLNKKVDDGFLDI



strain, without
WTYNAELLVLLENERTLDAHDS



foldon and with




K68C/R76C




mutation for




trimerization







>sp|P06821|M2_
MSLLTEVETPIRNEWGCRCNGSSDPLAIAANIIGILHLILWILDRL
439


I34A1 Matrix
FFKCIYRRFKYGLKGGPSTEGVPKSMREEYRKEQQSAVDADDGHFV



protein 2
SIELE



OS = Influenza A




virus (strain




A/Puerto




Rico/8/1934




H1N1) GN = M




PE = 3 SV = 1







A Matrix 1
MSLLTEVETYVLSIIPSGPLKAEIAQRLESVFAGKNTDLEALMEWL
440


(A/California/
KTRPILSPLTKGILGFVFTLTVPSERGLQRRRFVQNALNGNGDPNN



04/2009 (H1N1),
MDRAVKLYKKLKREITFHGAKEVSLSYSTGALASCMGLIYNRMGTV



ACP44152)
TTEAAFGLVCATCEQIADSQHRSHRQMATTTNPLIRHENRMVLAST




TAKAMEQMAGSSEQAAEAMEVANQTRQMVHAMRTIGTHPSSSAGLK




DDLLENLQAYQKRMGVQMQRFK






BHA10-2


METPAQLLFLLLLWLPDTTG
HVVKTATQGEVNVTGVIPLTTTPTGS


441




ANKSKPYYTGEHAKATGNCPIWVKTPLKLANGTKYGSAGSATQEAI




NKITKNLNSLSELEVKNLQRLSGASDETHNEILELDEKVDDLRADT




ISSQIELAVLLSNEGIINSEDEGTGGGYIPEAPRDGQAYVRKDGEW




VLLSTFL






BHA10-2*
HVVKTATQGEVNVTGVIPLTTTPTGSANKSKPYYTGEHAKATGNCP
442



IWVKTPLKLANGTKYGSAGSATQEAINKITKNLNSLSELEVKNLQR




LSGASDETHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSE




DEGTGGGYIPEAPRDGQAYVRKDGEWVLLSTFL






BHA10-3


METPAQLLFLLLLWLPDTTG
HVVKTATQGEVNVTGVIPLTTTPTGS


443




ANKSKPYYTGEHAKATGNCPIWVKTPLKLANGTKYGSAGSATQEAI




NKITKNLNSLSELEVKNLQRLSCASDETHNCILELDEKVDDLRADT




ISSLIELAVLLSNEGIINSEDE






BHA10-3*
HVVKTATQGEVNVTGVIPLTTTPTGSANKSKPYYTGEHAKATGNCP
444



IWVKTPLKLANGTKYGSAGSATQEAINKITKNLNSLSELEVKNLQR




LSCASDETHNCILELDEKVDDLRADTISSLIELAVLLSNEGIINSE




DE





5′UTR for each construct:


TCAAGCTTTTGGACCCTCGTACAGAAGCTAATACGACTCACTATAGGGAAATAAGAGAGAAAAGA


AGAGTAAGAAGAAATATAAGAGCCACC (SEQ ID NO: 445)


3′UTR for each construct:


TGATAATAGGCTGGAGCCTCGGTGGCCATGCTTCTTGCCCCTTGGGCCTCCCCCCAGCCCCTCCTCC


CCTTCCTGCACCCGTACCCCCGTGGTCTTTGAATAAAGTCTGAGTGGGCGGC (SEQ ID NO: 446)







The first underlined sequence for each of the amino acid sequences listed in Table 17, indicates a signal or secretory sequence, which may be substituted by an alternative sequence that achieves the same or similar function, or the signal or secretory sequence may be deleted.









TABLE 18







Influenza Nucleic Acids









Construct

SEQ


Description
ORF
ID NO:





B/Yamagata/16/
ATGAAGGCAATAATTGTACTACTCATGGTAGTAACATCCAACGCAG
447


1988 mHA
ATCGAATCTGCACTGGGATAACATCTTCAAACTCACCTCATGTGGT




CAAAACAGCTACTCAAGGGGAAGTTAATGTGACTGGTGTGATACCA




CTGACAACAACACCAACAAAATCTCATTTTGCAAATCTCAAAGGAA




CAAAGACCAGAGGGAAACTATGCCCAAACTGTCTCAACTGCACAGA




TCTGGATGTGGCCTTGGGCAGACCAATGTGTATGGGGACCATACCT




TCGGCAAAAGCTTCAATACTCCACGAAGTCAGACCTGTTACATCCG




GGTGCTTTCCTATAATGCACGACAGAACAAAAATCAGACAGCTACC




CAATCTTCTCAGAGGATATGAAAATATCAGATTATCAACCCATAAC




GTTATCAACGCAGAAAGGGCACCAGGAGGACCCTACAGACTTGGAA




CCTCAGGATCTTGCCCTAACGTTACCAGTAGAAACGGATTCTTCGC




AACAATGGCTTGGGCTGTCCCAAGGGACAACAAAACAGCAACGAAT




CCACTAACAGTAGAAGTACCATACATTTGCACAAAAGGAGAAGACC




AAATTACTGTTTGGGGGTTCCATTCTGATGACAAAACCCAAATGAA




AAACCTCTATGGAGACTCAAATCCTCAAAAGTTCACCTCATCTGCC




AATGGAGTAACCACACATTATGTTTCTCAGATTGGTGACTTCCCAA




ATCAAACAGAAGACGGAGGGCTACCACAAAGCGGCAGAATTGTTGT




TGATTACATGGTGCAAAAACCTGGGAAAACAGGAACAATTGTCTAT




CAAAGAGGTGTTTTGTTGCCTCAAAAGGTGTGGTGCGCAAGTGGCA




GGAGCAAGGTAATAAAAGGGTCCTTGCCTTTAATTGGTGAAGCAGA




TTGCCTTCACGAAAAATACGGTGGATTAAACAAAAGCAAGCCTTAC




TACACAGGAGAACATGCAAAAGCCATAGGAAATTGCCCAATATGGG




TGAAAACACCTTTGAAGCTTGCCAATGGAACCAAATATAGACCTCC




TGCAAAACTATTAAAGGAAAGGGGTTTCTTCGGAGCTATTGCTGGT




TTCTTAGAGGGAGGATGGGAAGGAATGATTGCAGGTTGGCACGGAT




ACACATCTCATGGAGCACATGGAGTGGCAGTGGCAGCAGACCTTAA




GAGCACGCAAGAAGCCATAAACAAGATAACAAAAAATCTCAATTCT




TTGAGTGAGCTAGAAGTAAAGAATCTTCAAAGACTAAGTGGTGCCA




TGGATGAACTCCACAACGAAATACTCGAGCTGGATGAGAAAGTGGA




TGATCTCAGAGCTGACACAATAAGCTCGCAAATAGAGCTTGCAGTC




TTGCTTTCCAACGAAGGAATAATAAACAGTGAAGATGAGCATCTAT




TGGCACTTGAGAGAAAACTAAAGAAAATGCTGGGTCCCTCTGCTGT




AGACATAGGGAATGGATGCTTCGAAACCAAACACAAGTGCAACCAG




ACCTGCTTAGACAGGATAGCTGCTGGCACCTTTAATGCAGGAGAAT




TTTCTCTTCCCACTTTTGATTCACTGAATATTACTGCTGCATCTTT




AAATGATGATGGATTGGATAATCATACTATACTGCTCTACTACTCA




ACTGCTGCTTCTAGTTTGGCCGTAACATTGATGATAGCTATTTTTA




TTGTTTATATGGTCTCCAGAGACAATGTTTCTTGCTCCATCTGTCT




A






B/Yamagata/16/
ATGAAGGCAATAATTGTACTACTCATGGTAGTAACATCCAACGCAG
448


1988 sHA
ATCGAATCTGCACTGGGATAACATCTTCAAACTCACCTCATGTGGT




CAAAACAGCTACTCAAGGGGAAGTTAATGTGACTGGTGTGATACCA




CTGACAACAACACCAACAAAATCTCATTTTGCAAATCTCAAAGGAA




CAAAGACCAGAGGGAAACTATGCCCAAACTGTCTCAACTGCACAGA




TCTGGATGTGGCCTTGGGCAGACCAATGTGTATGGGGACCATACCT




TCGGCAAAAGCTTCAATACTCCACGAAGTCAGACCTGTTACATCCG




GGTGCTTTCCTATAATGCACGACAGAACAAAAATCAGACAGCTACC




CAATCTTCTCAGAGGATATGAAAATATCAGATTATCAACCCATAAC




GTTATCAACGCAGAAAGGGCACCAGGAGGACCCTACAGACTTGGAA




CCTCAGGATCTTGCCCTAACGTTACCAGTAGAAACGGATTCTTCGC




AACAATGGCTTGGGCTGTCCCAAGGGACAACAAAACAGCAACGAAT




CCACTAACAGTAGAAGTACCATACATTTGCACAAAAGGAGAAGACC




AAATTACTGTTTGGGGGTTCCATTCTGATGACAAAACCCAAATGAA




AAACCTCTATGGAGACTCAAATCCTCAAAAGTTCACCTCATCTGCC




AATGGAGTAACCACACATTATGTTTCTCAGATTGGTGACTTCCCAA




ATCAAACAGAAGACGGAGGGCTACCACAAAGCGGCAGAATTGTTGT




TGATTACATGGTGCAAAAACCTGGGAAAACAGGAACAATTGTCTAT




CAAAGAGGTGTTTTGTTGCCTCAAAAGGTGTGGTGCGCAAGTGGCA




GGAGCAAGGTAATAAAAGGGTCCTTGCCTTTAATTGGTGAAGCAGA




TTGCCTTCACGAAAAATACGGTGGATTAAACAAAAGCAAGCCTTAC




TACACAGGAGAACATGCAAAAGCCATAGGAAATTGCCCAATATGGG




TGAAAACACCTTTGAAGCTTGCCAATGGAACCAAATATAGACCTCC




TGCAAAACTATTAAAGGAAAGGGGTTTCTTCGGAGCTATTGCTGGT




TTCTTAGAGGGAGGATGGGAAGGAATGATTGCAGGTTGGCACGGAT




ACACATCTCATGGAGCACATGGAGTGGCAGTGGCAGCAGACCTTAA




GAGCACGCAAGAAGCCATAAACAAGATAACAAAAAATCTCAATTCT




TTGAGTGAGCTAGAAGTAAAGAATCTTCAAAGACTAAGTGGTGCCA




TGGATGAACTCCACAACGAAATACTCGAGCTGGATGAGAAAGTGGA




TGATCTCAGAGCTGACACAATAAGCTCGCAAATAGAGCTTGCAGTC




TTGCTTTCCAACGAAGGAATAATAAACAGTGAAGATGAGCATCTAT




TGGCACTTGAGAGAAAACTAAAGAAAATGCTGGGTCCCTCTGCTGT




AGACATAGGGAATGGATGCTTCGAAACCAAACACAAGTGCAACCAG




ACCTGCTTAGACAGGATAGCTGCTGGCACCTTTAATGCAGGAGAAT




TTTCTCTTCCCACTTTTGATTCACTGAATATTACTGCTGCATCTTT




AAATGATGATGGATTGGATAATCATACT






B/Victoria/02/
ATGAAGGCAATAATTGTACTACTCATGGTAGTAACATCCAATGCAG
449


1987 mHA
ATCGAATCTGCACTGGGATAACATCGTCAAACTCACCCCATGTGGT




CAAAACTGCTACTCAAGGGGAAGTCAATGTGACTGGTGTGATACCA




CTGACAACAACACCCACCAAATCTCATTTTGCAAATCTCAAAGGAA




CAAAAACCAGAGGGAAACTATGCCCAAAGTGTCTCAACTGCACAGA




TCTGGACGTGGCCTTGGGCAGACCAAAGTGCACGGGGACCATACCT




TCGGCAAAAGCTTCAATACTCCACGAAGTCAAACCTGTTACATCTG




GGTGCTTTCCTATAATGCACGACAGAACAAAAATTAGACAGCTACC




CAATCTTCTCAGAGGATACGAACATATCAGGTTATCAACCCATAAC




GTTATCAACGCAGAAACGGCACCAGGAGGACCCTACAAAGTTGGAA




CCTCAGGGTCTTGCCCTAACGTTACCAATGGAAACGGATTCTTCGC




AACAATGGCTTGGGCTGTCCCAAAAAACGACAACAACAAAACAGCA




ACAAATCCATTAACAGTAGAAGTACCATACATTTGTACAGAAGGAG




AAGACCAAATTACTGTTTGGGGGTTCCACTCTGATAACGAAGCCCA




AATGGTAAAACTCTATGGAGACTCAAAGCCTCAGAAGTTCACCTCA




TCTGCCAACGGAGTGACCACACATTACGTTTCACAGATTGGTGGCT




TCCCAAATCAAGCAGAAGACGGAGGGCTACCACAAAGCGGTAGAAT




TGTTGTTGATTACATGGTGCAAAAATCTGGAAAAACAGGAACAATT




ACCTACCAAAGAGGTATTTTATTGCCTCAAAAAGTGTGGTGCGCAA




GTGGCAGGAGCAAGGTAATAAAAGGGTCCTTGCCTTTAATTGGCGA




AGCAGATTGCCTCCACGAAAAATACGGTGGATTAAACAAAAGCAAG




CCTTACTACACAGGGGAACATGCAAAAGCCATAGGAAATTGCCCAA




TATGGGTGAAAACACCCTTGAAGCTGGCCAATGGAACCAAATATAG




ACCTCCTGCAAAACTATTAAAGGAAAAGGGTTTCTTCGGAGCTATT




GCTGGTTTCTTAGAAGGAGGATGGGAAGGAATGATTGCAGGTTGGC




ACGGATACACATCCCATGGAGCACATGGAGTAGCAGTGGCAGCAGA




CCTTAAGAGTACGCAAGAAGCCATAAACAAGATAACAAAAAATCTC




AATTCTTTGAGTGAGCTGGAAGTAAAGAATCTTCAAAGACTAAGCG




GTGCCATGGATGAACTCCACAACAAAATACTCGAACTGGATGAGAA




AGTGGATGATCTCAGAGCTGATACAATAAGCTCGCAAATAGAGCTC




GCAGTCTTGCTTTCCAACGAAGGAATAATAAACAGTGAAGATGAGC




ATCTCTTGGCGCTTGAAAGAAAACTGAAGAAAATGCTGGGCCCCTC




TGCTGTAGAGATAGGGAATGGATGCTTCGAAACCAAACACAAGTGC




AACCAGACCTGCCTCGACAGAATAGCTGCTGGCACCTTTAATGCAG




GAGAATTTTCTCTCCCCACCTTTGATTCACTAAATATTACTGCTGC




ATCTTTAAATGATGATGGATTGGATAATCATACTATACTGCTTTAC




TACTCAACTGCTGCTTCCAGTTTGGCTGTAACATTGATGATAGCTA




TCTTTATTGTTTATATGGTCTCCAGAGACAATGTTTCTTGCTCCAT




CTGTCTA






B/Victoria/02/
ATGAAGGCAATAATTGTACTACTCATGGTAGTAACATCCAATGCAG
450


1987 sHA
ATCGAATCTGCACTGGGATAACATCGTCAAACTCACCCCATGTGGT




CAAAACTGCTACTCAAGGGGAAGTCAATGTGACTGGTGTGATACCA




CTGACAACAACACCCACCAAATCTCATTTTGCAAATCTCAAAGGAA




CAAAAACCAGAGGGAAACTATGCCCAAAGTGTCTCAACTGCACAGA




TCTGGACGTGGCCTTGGGCAGACCAAAGTGCACGGGGACCATACCT




TCGGCAAAAGCTTCAATACTCCACGAAGTCAAACCTGTTACATCTG




GGTGCTTTCCTATAATGCACGACAGAACAAAAATTAGACAGCTACC




CAATCTTCTCAGAGGATACGAACATATCAGGTTATCAACCCATAAC




GTTATCAACGCAGAAACGGCACCAGGAGGACCCTACAAAGTTGGAA




CCTCAGGGTCTTGCCCTAACGTTACCAATGGAAACGGATTCTTCGC




AACAATGGCTTGGGCTGTCCCAAAAAACGACAACAACAAAACAGCA




ACAAATCCATTAACAGTAGAAGTACCATACATTTGTACAGAAGGAG




AAGACCAAATTACTGTTTGGGGGTTCCACTCTGATAACGAAGCCCA




AATGGTAAAACTCTATGGAGACTCAAAGCCTCAGAAGTTCACCTCA




TCTGCCAACGGAGTGACCACACATTACGTTTCACAGATTGGTGGCT




TCCCAAATCAAGCAGAAGACGGAGGGCTACCACAAAGCGGTAGAAT




TGTTGTTGATTACATGGTGCAAAAATCTGGAAAAAGAGGAACAATT




ACCTACCAAAGAGGTATTTTATTGCCTCAAAAAGTGTGGTGCGCAA




GTGGCAGGAGCAAGGTAATAAAAGGGTCCTTGCCTTTAATTGGCGA




AGCAGATTGCCTCCACGAAAAATACGGTGGATTAAACAAAAGCAAG




CCTTACTACACAGGGGAACATGCAAAAGCCATAGGAAATTGCCCAA




TATGGGTGAAAACACCCTTGAAGCTGGCCAATGGAACCAAATATAG




ACCTCCTGCAAAACTATTAAAGGAAAAGGGTTTCTTCGGAGCTATT




GCTGGTTTCTTAGAAGGAGGATGGGAAGGAATGATTGCAGGTTGGC




ACGGATACACATCCCATGGAGCACATGGAGTAGCAGTGGCAGCAGA




CCTTAAGAGTACGCAAGAAGCCATAAACAAGATAACAAAAAATCTC




AATTCTTTGAGTGAGCTGGAAGTAAAGAATCTTCAAAGACTAAGCG




GTGCCATGGATGAACTCCACAACAAAATACTCGAACTGGATGAGAA




AGTGGATGATCTCAGAGCTGATACAATAAGCTCGCAAATAGAGCTC




GCAGTCTTGCTTTCCAACGAAGGAATAATAAACAGTGAAGATGAGC




ATCTCTTGGCGCTTGAAAGAAAACTGAAGAAAATGCTGGGCCCCTC




TGCTGTAGAGATAGGGAATGGATGCTTCGAAACCAAACACAAGTGC




AACCAGACCTGCCTCGACAGAATAGCTGCTGGCACCTTTAATGCAG




GAGAATTTTCTCTCCCCACCTTTGATTCACTAAATATTACTGCTGC




ATCTTTAAATGATGATGGATTGGATAATCATACT






B/Brisbane/60/
ATGAAGGCAATAATTGTACTACTCATGGTAGTAACATCCAATGCAG
451


2008 mHA
ATCGAATCTGCACTGGGATAACATCGTCAAACTCACCACATGTCGT




CAAAACTGCTACTCAAGGGGAGGTCAATGTGACTGGTGTAATACCA




CTGACAACAACACCCACCAAATCTCATTTTGCAAATCTCAAAGGAA




CAGAAACCAGGGGGAAACTATGCCCAAAATGCCTCAACTGCACAGA




TCTGGACGTAGCCTTGGGCAGACCAAAATGCACGGGGAAAATACCC




TCGGCAAGAGTTTCAATACTCCATGAAGTCAGACCTGTTACATCTG




GGTGCTTTCCTATAATGCACGACAGAACAAAAATTAGACAGCTGCC




TAACCTTCTCCGAGGATACGAACATATCAGGTTATCAACCCATAAC




GTTATCAATGCAGAAAATGCACCAGGAGGACCCTACAAAATTGGAA




CCTCAGGGTCTTGCCCTAACATTACCAATGGAAACGGATTTTTCGC




AACAATGGCTTGGGCCGTCCCAAAAAACGACAAAAACAAAACAGCA




ACAAATCCATTAACAATAGAAGTACCATACATTTGTACAGAAGGAG




AAGACCAAATTACCGTTTGGGGGTTCCACTCTGACGACGAGACCCA




AATGGCAAAGCTCTATGGGGACTCAAAGCCCCAGAAGTTCACCTCA




TCTGCCAACGGAGTGACCACACATTACGTTTCACAGATTGGTGGCT




TCCCAAATCAAACAGAAGACGGAGGACTACCACAAAGTGGTAGAAT




TGTTGTTGATTACATGGTGCAAAAATCTGGGAAAACAGGAACAATT




ACCTATCAAAGGGGTATTTTATTGCCTCAAAAGGTGTGGTGCGCAA




GTGGCAGGAGCAAGGTAATAAAAGGATCCTTGCCTTTAATTGGAGA




AGCAGATTGCCTCCACGAAAAATACGGTGGATTAAACAAAAGCAAG




CCTTACTACACAGGGGAACATGCAAAGGCCATAGGAAATTGCCCAA




TATGGGTGAAAACACCCTTGAAGCTGGCCAATGGAACCAAATATAG




ACCTCCTGCAAAACTATTAAAGGAAAGGGGTTTCTTCGGAGCTATT




GCTGGTTTCTTAGAAGGAGGATGGGAAGGAATGATTGCAGGTTGGC




ACGGATACACATCCCATGGGGCACATGGAGTAGCGGTGGCAGCAGA




CCTTAAGAGCACTCAAGAGGCCATAAACAAGATAACAAAAAATCTC




AACTCTTTGAGTGAGCTGGAAGTAAAGAATCTTCAAAGACTAAGCG




GTGCCATGGATGAACTCCACAACGAAATACTAGAACTAGATGAGAA




AGTGGATGATCTCAGAGCTGATACAATAAGCTCACAAATAGAACTC




GCAGTCCTGCTTTCCAATGAAGGAATAATAAACAGTGAAGATGAAC




ATCTCTTGGCGCTTGAAAGAAAGCTGAAGAAAATGCTGGGCCCCTC




TGCTGTAGAGATAGGGAATGGATGCTTTGAAACCAAACACAAGTGC




AACCAGACCTGTCTCGACAGAATAGCTGCTGGTACCTTTGATGCAG




GAGAATTTTCTCTCCCCACCTTTGATTCACTGAATATTACTGCTGC




ATCTTTAAATGACGATGGATTGGATAATCATACTATACTGCTTTAC




TACTCAACTGCTGCCTCCAGTTTGGCTGTAACACTGATGATAGCTA




TCTTTGTTGTTTATATGGTCTCCAGAGACAATGTTTCTTGCTCCAT




CTGTCTA






B/Brisbane/60/
ATGAAGGCAATAATTGTACTACTCATGGTAGTAACATCCAATGCAG
452


2008 sHA
ATCGAATCTGCACTGGGATAACATCGTCAAACTCACCACATGTCGT




CAAAACTGCTACTCAAGGGGAGGTCAATGTGACTGGTGTAATACCA




CTGACAACAACACCCACCAAATCTCATTTTGCAAATCTCAAAGGAA




CAGAAACCAGGGGGAAACTATGCCCAAAATGCCTCAACTGCACAGA




TCTGGACGTAGCCTTGGGCAGACCAAAATGCACGGGGAAAATACCC




TCGGCAAGAGTTTCAATACTCCATGAAGTCAGACCTGTTACATCTG




GGTGCTTTCCTATAATGCACGACAGAACAAAAATTAGACAGCTGCC




TAACCTTCTCCGAGGATACGAACATATCAGGTTATCAACCCATAAC




GTTATCAATGCAGAAAATGCACCAGGAGGACCCTACAAAATTGGAA




CCTCAGGGTCTTGCCCTAACATTACCAATGGAAACGGATTTTTCGC




AACAATGGCTTGGGCCGTCCCAAAAAACGACAAAAACAAAACAGCA




ACAAATCCATTAACAATAGAAGTACCATACATTTGTACAGAAGGAG




AAGACCAAATTACCGTTTGGGGGTTCCACTCTGACGACGAGACCCA




AATGGCAAAGCTCTATGGGGACTCAAAGCCCCAGAAGTTCACCTCA




TCTGCCAACGGAGTGACCACACATTACGTTTCACAGATTGGTGGCT




TCCCAAATCAAACAGAAGACGGAGGACTACCACAAAGTGGTAGAAT




TGTTGTTGATTACATGGTGCAAAAATCTGGGAAAACAGGAACAATT




ACCTATCAAAGGGGTATTTTATTGCCTCAAAAGGTGTGGTGCGCAA




GTGGCAGGAGCAAGGTAATAAAAGGATCCTTGCCTTTAATTGGAGA




AGCAGATTGCCTCCACGAAAAATACGGTGGATTAAACAAAAGCAAG




CCTTACTACACAGGGGAACATGCAAAGGCCATAGGAAATTGCCCAA




TATGGGTGAAAACACCCTTGAAGCTGGCCAATGGAACCAAATATAG




ACCTCCTGCAAAACTATTAAAGGAAAGGGGTTTCTTCGGAGCTATT




GCTGGTTTCTTAGAAGGAGGATGGGAAGGAATGATTGCAGGTTGGC




ACGGATACACATCCCATGGGGCACATGGAGTAGCGGTGGCAGCAGA




CCTTAAGAGCACTCAAGAGGCCATAAACAAGATAACAAAAAATCTC




AACTCTTTGAGTGAGCTGGAAGTAAAGAATCTTCAAAGACTAAGCG




GTGCCATGGATGAACTCCACAACGAAATACTAGAACTAGATGAGAA




AGTGGATGATCTCAGAGCTGATACAATAAGCTCACAAATAGAACTC




GCAGTCCTGCTTTCCAATGAAGGAATAATAAACAGTGAAGATGAAC




ATCTCTTGGCGCTTGAAAGAAAGCTGAAGAAAATGCTGGGCCCCTC




TGCTGTAGAGATAGGGAATGGATGCTTTGAAACCAAACACAAGTGC




AACCAGACCTGTCTCGACAGAATAGCTGCTGGTACCTTTGATGCAG




GAGAATTTTCTCTCCCCACCTTTGATTCACTGAATATTACTGCTGC




ATCTTTAAATGACGATGGATTGGATAATCATACT






B/Phuket/3073/
ATGAAGGCAATAATTGTACTACTCATGGTAGTAACATCCAATGCAG
453


2013 mHA
ATCGAATCTGCACTGGGATAACATCTTCAAACTCACCTCATGTGGT




CAAAACAGCTACTCAAGGGGAGGTCAATGTGACTGGCGTGATACCA




CTGACAACAACACCAACAAAATCTTATTTTGCAAATCTCAAAGGAA




CAAGGACCAGAGGGAAACTATGCCCGGACTGTCTCAACTGTACAGA




TCTGGATGTGGCCTTGGGCAGGCCAATGTGTGTGGGGACCACACCT




TCTGCTAAAGCTTCAATACTCCACGAGGTCAGACCTGTTACATCCG




GGTGCTTTCCTATAATGCACGACAGAACAAAAATCAGGCAACTACC




CAATCTTCTCAGAGGATATGAAAAGATCAGGTTATCAACCCAAAAC




GTTATCGATGCAGAAAAAGCACCAGGAGGACCCTACAGACTTGGAA




CCTCAGGATCTTGCCCTAACGCTACCAGTAAAATCGGATTTTTCGC




AACAATGGCTTGGGCTGTCCCAAAGGACAACTACAAAAATGCAACG




AACCCACTAACAGTAGAAGTACCATACATTTGTACAGAAGGGGAAG




ACCAAATTACTGTTTGGGGGTTCCATTCAGACAACAAAACCCAAAT




GAAGAGCCTCTATGGAGACTCAAATCCTCAAAAGTTCACCTCATCT




GCTAATGGAGTAACCACACATTATGTTTCTCAGATTGGCGACTTCC




CAGATCAAACAGAAGACGGAGGACTACCACAAAGCGGCAGAATTGT




TGTTGATTACATGATGCAAAAACCTGGGAAAACAGGAACAATTGTC




TATCAAAGAGGTGTTTTGTTGCCTCAAAAGGTGTGGTGCGCGAGTG




GCAGGAGCAAAGTAATAAAAGGGTCATTGCCTTTAATTGGTGAAGC




AGATTGCCTTCATGAAAAATACGGTGGATTAAACAAAAGCAAGCCT




TACTACACAGGAGAACATGCAAAAGCCATAGGAAATTGCCCAATAT




GGGTAAAAACACCTTTGAAGCTTGCCAATGGAACCAAATATAGACC




TCCTGCAAAACTATTGAAGGAAAGGGGTTTCTTCGGAGCTATTGCT




GGTTTCCTAGAAGGAGGATGGGAAGGAATGATTGCAGGTTGGCACG




GATACACATCTCACGGAGCACATGGAGTGGCAGTGGCGGCAGACCT




TAAGAGTACACAAGAAGCTATAAATAAGATAACAAAAAATCTCAAT




TCTTTGAGTGAGCTAGAAGTAAAGAACCTTCAAAGACTAAGTGGTG




CCATGGATGAACTCCACAACGAAATACTCGAGCTGGATGAGAAAGT




GGATGATCTCAGAGCTGACACTATAAGCTCACAAATAGAACTTGCA




GTCTTGCTTTCCAACGAAGGAATAATAAACAGTGAAGACGAGCATC




TATTGGCACTTGAGAGAAAACTAAAGAAAATGCTGGGTCCCTCTGC




TGTAGACATAGGAAACGGATGCTTCGAAACCAAACACAAATGCAAC




CAGACCTGCTTAGACAGGATAGCTGCTGGCACCTTTGATGCAGGAG




AATTTTCTCTCCCCACTTTTGATTCATTGAACATTACTGCTGCATC




TTTAAATGATGATGGATTGGATAACCATACTATACTGCTCTATTAC




TCAACTGCTGCTTCTAGTTTGGCTGTAACATTAATGCTAGCTATTT




TTATTGTTTATATGGTCTCCAGAGACAACGTTTCATGCTCCATCTG




TCTA





5′UTR for each construct:


TCAAGCTTTTGGACCCTCGTACAGAAGCTAATACGACTCACTATAGGGAAATAAGAGAGAAAAGA


AGAGTAAGAAGAAATATAAGAGCCACC (SEQ ID NO: 445)


3′UTR for each construct:


TGATAATAGGCTGGAGCCTCGGTGGCCATGCTTCTTGCCCCTTGGGCCTCCCCCCAGCCCCTCCTCC


CCTTCCTGCACCCGTACCCCCGTGGTCTTTGAATAAAGTCTGAGTGGGCGGC (SEQ ID NO: 446)







It should be understood that the 5′ and/or 3′ UTR for each construct may be omitted, modified or substituted for a different UTR sequences in any one of the vaccines as provided herein.









TABLE 19







Examples of Wild Type Hemagglutinin Antigens









Protein/

SEQ


Strain
Nucleic Acid Sequence
ID NO:





H1
AGCAAAAGCAGGGGAAAATAAAAACAACCAAAATGAAGGCAAACCTACTG
454



GTCCTGTTATGTGCACTTGCAGCTGCAGATGCAGACACAATATGTATAGG




CTACCATGCGAACAATTCAACCGACACTGTTGACACAGTGCTCGAGAAGA




ATGTGACAGTGACACACTCTGTTAACCTGCTCGAAGACAGCCACAACGGA




AAACTATGTAGATTAAAAGGAATAGCCCCACTACAATTGGGGAAATGTAA




CATCGCCGGATGGCTCTTGGGAAACCCAGAATGCGACCCACTGCTTCCAG




TGAGATCATGGTCCTACATTGTAGAAACACCAAACTCTGAGAATGGAATA




TGTTATCCAGGAGATTTCATCGACTATGAGGAGCTGAGGGAGCAATTGAG




CTCAGTGTCATCATTCGAAAGATTCGAAATATTTCCCAAAGAAAGCTCAT




GGCCCAACCACAACACAACCAAAGGAGTAACGGCAGCATGCTCCCATGCG




GGGAAAAGCAGTTTTTACAGAAATTTGCTATGGCTGACGGAGAAGGAGGG




CTCATACCCAAAGCTGAAAAATTCTTATGTGAACAAGAAAGGGAAAGAAG




TCCTTGTACTGTGGGGTATTCATCACCCGTCTAACAGTAAGGATCAACAG




AATATCTATCAGAATGAAAATGCTTATGTCTCTGTAGTGACTTCAAATTA




TAACAGGAGATTTACCCCGGAAATAGCAGAAAGACCCAAAGTAAGAGATC




AAGCTGGGAGGATGAACTATTACTGGACCTTGCTAAAACCCGGAGACACA




ATAATATTTGAGGCAAATGGAAATCTAATAGCACCAAGGT




ATGCTTTCGCACTGAGTAGAGGCTTTGGGTCCGGCATCATCACCTCAAAC




GCATCAATGCATGAGTGTAACACGAAGTGTCAAACACCCCTGGGAGCTAT




AAACAGCAGTCTCCCTTTCCAGAATATACACCCAGTCACAATAGGAGAGT




GCCCAAAATACGTCAGGAGTGCCAAATTGAGGATGGTTACAGGACTAAGG




AACATTCCGTCCATTCAATCCAGAGGTCTATTTGGAGCCATTGCCGGTTT




TATTGAAGGGGGATGGACTGGAATGATAGATGGATGGTACGGTTATCATC




ATCAGAATGAACAGGGATCAGGCTATGCAGCGGATCAAAAAAGCACACAA




AATGCCATTAACGGGATTACAAACAAGGTGAACTCTGTTATCGAGAAAAT




GAACATTCAATTCACAGCTGTGGGTAAAGAATTCAACAAATTAGAAAAAA




GGATGGAAAATTTAAATAAAAAAGTTGATGATGGATTTCTGGACATTTGG




ACATATAATGCAGAATTGTTAGTTCTACTGGAAAATGAAAGGACTCTGGA




TTTCCATGACTCAAATGTGAAGAATCTGTATGAGAAAGTAAAAAGCCAAT




TAAAGAATAATGCCAAAGAAATCGGAAATGGATGTTTTGAGTTCTACCAC




AAGTGTGACAATGAATGCATGGAAAGTGTAAGAAATGGGACTTATGATTA




TCCCAAATATTCAGAAGAGTCAAAGTTGAACAGGGAAAAGGTAGATGGAG




TGAAATTGGAATCAATGGGGATCTATCAGATTCTGGCGATCTACTCAACT




GTCGCCAGTTCACTGGTGCTTTTGGTCTCCCTGGGGGCAATCAGTTTCTG




GATGTGTTCTAATGGATCTTTGCAGTGCAGAATATGCATCTGAGATTAGA




ATTTCAGAAATATGAGGAAAAACACCCTTGTTTCTACT






H7
AGCGAAAGCAGGGGATACAAAATGAACACTCAAATCCTGGTATTCGCTCT
455



GATTGCGATCATTCCAACAAATGCAGACAAAATCTGCCTCGGACATCATG




CCGTGTCAAACGGAACCAAAGTAAACACATTAACTGAAAGAGGAGTGGAA




GTCGTCAATGCAACTGAAACAGTGGAACGAACAAACATCCCCAGGATCTG




CTCAAAAGGGAAAAGGACAGTTGACCTCGGTCAATGTGGACTCCTGGGGA




CAATCACTGGACCACCTCAATGTGACCAATTCCTAGAATTTTCAGCCGAT




TTAATTATTGAGAGGCGAGAAGGAAGTGATGTCTGTTATCCTGGGAAATT




CGTGAATGAAGAAGCTCTGAGGCAAATTCTCAGAGAATCAGGCGGAATTG




ACAAGGAAGCAATGGGATTCACATACAGTGGAATAAGAACTAATGGAGCA




ACCAGTGCATGTAGGAGATCAGGATCTTCATTCTATGCAGAAATGAAATG




GCTCCTGTCAAACACAGATGATGCTGCATTCCCGCAGATGACTAAGTCAT




ATAAAAATACAAGAAAAAGCCCAGCTCTAATAGTATGGGGGATCCATCAT




TCCGTATCAACTGCAGAGCAAACCAAGCTATATGGGAGTGGAAACAAACT




GGTGACAGTTGGGAGTTCTAATTATCAACAATCTTTTGTACCGAGTCCAG




GAGCGAGACCACAAGTTAATGGTCTATCTGGAAGAATTGACTTTCATTGG




CTAATGCTAAATCCCAATGATACAGTCACTTTCAGTTTCAATGGGGCTTT




CATAGCTCCAGACCGTGCAAGCTTCCTGAGAGGAAAATCTATGGGAATCC




AGAGTGGAGTACAGGTTGATGCCAATTGTGAAGGGGACTGCTATCATAGT




GGAGGGACAATAATAAGTAACTTGCCATTTCAGAACATAGATAGCAGGGC




AGTTGGAAAATGTCCGAGATATGTTAAGCAAAGGAGTCTGCTGCTAGCAA




CAGGGATGAAGAATGTTCCTGAGATTCCAAAGGGAAGAGGCCTATTTGGT




GCTATAGCGGGTTTCATTGAAAATGGATGGGAAGGCCTAATTGATGGTTG




GTATGGTTTCAGACACCAGAATGCACAGGGAGAGGGAACTGCTGCAGATT




ACAAAAGCACTCAATCGGCAATTGATCAAATAACAGGAAAATTAAACCGG




CTTATAGAAAAAACCAACCAACAATTTGAGTTGATAGACAATGAATTCAA




TGAGGTAGAGAAGCAAATCGGTAATGTGATAAATTGGACCAGAGATTCTA




TAACAGAAGTGTGGTCATACAATGCTGAACTCTTGGTAGCAATGGAGAAC




CAGCATACAATTGATCTGGCTGATTCAGAAATGGACAAACTGTACGAACG




AGTGAAAAGACAGCTGAGAGAGAATGCTGAAGAAGATGGCACTGGTTGCT




TTGAAATATTTCACAAGTGTGATGATGACTGTATGGCCAGTATTAGAAAT




AACACCTATGATCACAGCAAATACAGGGAAGAGGCAATGCAAAATAGAAT




ACAGATTGACCCAGTCAAACTAAGCAGCGGCTACAAAGATGTGATACTTT




GGTTTAGCTTCGGGGCATCATGTTTCATACTTCTAGCCATTGTAATGGGC




CTTGTCTTCATATGTGTAAAGAATGGAAACATGCGGTGCACTATTTGTAT




ATAAGTTTGGAAAAAAACACCCTTGTTTCTAC






H10
ATGTACAAAATAGTAGTGATAATCGCGCTCCTTGGAGCTGTGAAAGGTCT
456



TGATAAAATCTGTCTAGGACATCATGCAGTGGCTAATGGGACCATCGTAA




AGACTCTCACAAACGAACAGGAAGAGGTAACCAACGCTACTGAAACAGTG




GAGAGTACAGGCATAAACAGATTATGTATGAAAGGAAGAAAACATAAAGA




CCTGGGCAACTGCCATCCAATAGGGATGCTAATAGGGACTCCAGCTTGTG




ATCTGCACCTTACAGGGATGTGGGACACTCTCATTGAACGAGAGAATGCT




ATTGCTTACTGCTACCCTGGAGCTACTGTAAATGTAGAAGCACTAAGGCA




GAAGATAATGGAGAGTGGAGGGATCAACAAGATAAGCACTGGCTTCACTT




ATGGATCTTCCATAAACTCGGCCGGGACCACTAGAGCGTGCATGAGGAAT




GGAGGGAATAGCTTTTATGCAGAGCTTAAGTGGCTGGTATCAAAGAGCAA




AGGACAAAACTTCCCTCAGACCACGAACACTTACAGAAATACAGACACGG




CTGAACACCTCATAATGTGGGGAATTCATCACCCTTCTAGCACTCAAGAG




AAGAATGATCTATATGGAACACAATCACTGTCCATATCAGTCGGGAGTTC




CACTTACCGGAACAATTTTGTTCCGGTTGTTGGAGCAAGACCTCAGGTCA




ATGGACAAAGTGGCAGAATTGATTTTCACTGGACACTAGTACAGCCAGGT




GACAACATCACCTTCTCACACAATGGGGGCCTGATAGCACCGAGCCGAGT




TAGCAAATTAATTGGGAGGGGATTGGGAATCCAATCAGACGCACCAATAG




ACAATAATTGTGAGTCCAAATGTTTTTGGAGAGGGGGTTCTATAAATACA




AGGCTTCCCTTTCAAAATTTGTCACCAAGAACAGTGGGTCAGTGTCCTAA




ATATGTGAACAGAAGAAGCTTGATGCTTGCAACAGGAATGAGAAACGTAC




CAGAACTAATACAAGGGAGAGGTCTATTTGGTGCAATAGCAGGGTTTTTA




GAGAATGGGTGGGAAGGAATGGTAGATGGCTGGTATGGTTTCAGACATCA




AAATGCTCAGGGCACAGGCCAGGCCGCTGATTACAAGAGTACTCAGGCAG




CTATTGATCAAATCACTGGGAAACTGAATAGACTTGTTGAAAAAACCAAT




ACTGAGTTCGAGTCAATAGAATCTGAGTTCAGTGAGATCGAACACCAAAT




CGGTAACGTCATCAATTGGACTAAGGATTCAATAACCGACATTTGGACTT




ATCAGGCTGAGCTGTTGGTGGCAATGGAGAACCAGCATACAATCGACATG




GCTGACTCAGAGATGTTGAATCTATATGAAAGAGTGAGGAAACAACTAAG




GCAGAATGCAGAAGAAGATGGGAAAGGATGTTTTGAGATATATCATGCTT




GTGATGATTCATGCATGGAGAGCATAAGAAACAACACCTATGACCATTCA




CAGTACAGAGAGGAAGCTCTTTTGAACAGATTGAATATCAACCCAGTGAC




ACTCTCTTCTGGATATAAAGACATCATTCTCTGGTTTAGCTTCGGGGCAT




CATGTTTTGTTCTTCTAGCCGTTGTCATGGGTCTTTTCTTTTTCTGTCTG




AAGAATGGAAACATGCGATGCACAATCTGTATTTAG
















TABLE 20







Additional Flu Constructs











SEQ


Name
Sequence
ID NO:





MRK_LZ_
ATGGCCAGCCAGGGCACCAAGAGAAGCTACGAGCAGATGGAG
457


NP-H3N2
ACCGACGGCGAGAGACAGAACGCCACCGAGATCAGAGCCAGC



SQ-031687
GTGGGCAAGATGATCGACGGCATCGGCAGATTCTACATCCAGA



CX-003145
TGTGCACCGAGCTCAAGCTGAGCGACTACGAGGGCAGACTGAT




CCAGAACAGCCTGACCATCGAAAGAATGGTTCTGAGCGCCTTC




GACGAGAGAAGAAACAGATACCTGGAGGAGCACCCCAGCGCC




GGCAAGGACCCCAAGAAGACCGGCGGCCCCATCTACAAGAGA




GTGGACGGCAGATGGATGAGAGAGCTGGTGCTGTACGACAAGG




AGGAGATCAGAAGAATCTGGAGACAGGCCAACAACGGCGACG




ACGCCACCGCCGGCCTGACCCACATGATGATCTGGCACAGCAA




CCTGAACGACACCACCTACCAGAGAACCAGAGCCCTGGTGAGA




ACCGGCATGGACCCCAGAATGTGCAGCTTAATGCAGGGCAGCA




CCCTGCCCAGAAGATCCGGCGCCGCTGGTGCCGCCGTCAAGGG




CATCGGCACCATGGTGATGGAGCTGATCCGCATGATCAAGCGC




GGCATCAACGACAGAAACTTCTGGAGAGGCGAAAACGGCAGA




AAGACCAGAAGCGCCTACGAGAGAATGTGCAACATCCTGAAGG




GCAAGTTCCAGACCGCCGCCCAAAGAGCCATGATGGACCAGGT




GAGAGAGAGCAGAAACCCCGGCAACGCCGAGATCGAAGACCT




GATCTTCAGCGCCAGATCGGCCCTGATCCTGAGAGGCAGCGTG




GCCCACAAGAGCTGCCTGCCCGCCTGCGTGTATGGCCCCGCCGT




GAGCAGCGGCTACAACTTCGAGAAGGAGGGCTACAGCCTGGTG




GGCATCGACCCCTTCAAGCTGCTGCAGAACTCTCAGGTGTATAG




CCTGATCAGACCCAACGAGAACCCCGCCCACAAGAGCCAGCTG




GTGTGGATGGCCTGCCACAGCGCCGCCTTCGAGGACCTGAGAC




TGCTGAGCTTCATCAGAGGTACCAAGGTGTCCCCCAGAGGCAA




GCTGAGCACCAGAGGTGTGCAGATCGCCAGCAATGAGAACATG




GACAATATGGAGAGCAGCACCCTGGAGCTAAGAAGCAGGTACT




GGGCCATCCGGACCAGAAGCGGCGGCAATACCAACCAGCAGA




GAGCCAGCGCCGGCCAGATCAGCGTGCAGCCCACCTTCAGCGT




GCAGAGAAACCTGCCCTTTGAGAAGAGCACCGTGATGGCCGCC




TTCACCGGCAACACCGAGGGCAGAACCAGCGACATGAGAGCCG




AGATCATCAGAATGATGGAGGGCGCCAAGCCCGAGGAGGTGA




GCTTTAGAGGCAGAGGCGTGTTCGAGCTGAGCGACGAGAAGGC




CACCAACCCAATTGTGCCCAGCTTCGACATGTCGAACGAGGGC




AGCTACTTCTTCGGCGACAACGCCGAGGAGTACGACAAC






MRK_LZ_
MASQGTKRSYEQMETDGERQNATEIRASVGKMIDGIGRFYIQMCT
458


NP-H3N2
ELKLSDYEGRLIQNSLTIERMVLSAFDERRNRYLEEHPSAGKDPKK



SQ-031687
TGGPIYKRVDGRWMRELVLYDKEEIRRIWRQANNGDDATAGLTH



CX-003145
MMIWHSNLNDTTYQRTRALVRTGMDPRMCSLMQGSTLPRRSGA




AGAAVKGIGTMVMELIRMIKRGINDRNFWRGENGRKTRSAYERM




CNILKGKFQTAAQRAMMDQVRESRNPGNAEIEDLIFSARSALILRG




SVAHKSCLPACVYGPAVSSGYNFEKEGYSLVGIDPFKLLQNSQVY




SLIRPNENPAHKSQLVWMACHSAAFEDLRLLSFIRGTKVSPRGKLS




TRGVQIASNENMDNMESSTLELRSRYWAIRTRSGGNTNQQRASAG




QISVQPTFSVQRNLPFEKSTVMAAFTGNTEGRTSDMRAEIIRMMEG




AKPEEVSFRGRGVFELSDEKATNPIVPSFDMSNEGSYFFGDNAEEY




DN






MRK_LZ_
ATGGAGACCCCCGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGCT
459


NIHGen6H
GCCCGACACCACCGGCGACACCATCTGCATCGGCTACCACGCC



ASS-TM2
AACAACAGCACCGACACCGTGGACACCGTGCTGGAGAAGAAC



SQ-034074
GTGACCGTGACCCACAGCGTGAACCTGGGCAGCGGCCTGAGGA



CX-000553
TGGTGACCGGCCTGAGGAACATCCCCCAGAGGGAGACCAGGGG




CCTGTTCGGCGCCATCGCCGGCTTCATCGAGGGCGGCTGGACC




GGCATGGTGGACGGCTGGTACGGCTACCACCACCAGAACGAGC




AGGGCAGCGGCTACGCCGCCGACCAGAAGAGCACCCAGAACG




CCATCAACGGCATCACCAACATGGTGAACAGCGTGATCGAGAA




GATGGGCAGCGGCGGCAGCGGCACCGACCTGGCCGAGCTGCTG




GTGCTGCTGCTGAACGAGAGGACCCTGGACTTCCACGACAGCA




ACGTGAAGAACCTGTACGAGAAGGTGAAGAGCCAGCTGAAGA




ACAACGCCAAGGAGATCGGCAACGGCTGCTTCGAGTTCTACCA




CAAGTGCAACAACGAGTGCATGGAGAGCGTGAAGAACGGCAC




CTACGACTACCCCAAGTACAGCGAGGAGAGCAAGCTGAACAGG




GAGAAGATCGACGGAGTGAAATTGGAATCAATGGGGGTCTATC




AGATCCTGGCCATCTACAGCACCGTGGCCAGCAGCCTGGTGCT




GCTGGTGAGCCTGGGCGCCATCAGCTTCTGGATGTGCAGCAAC




GGCAGCCTGCAGTGCAGAATCTGCATC






MRK_LZ_

METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDTVDTVLEKNVT

460


NIHGen6H
VTHSVNLGSGLRMVTGLRNIPQRETRGLFGAIAGFIEGGWTGMVD



ASS-TM2
GWYGYHHQNEQGSGYAADQKSTQNAINGITNMVNSVIEKMGSG



SQ-034074
GSGTDLAELLVLLLNERTLDFHDSNVKNLYEKVKSQLKNNAKEIG



CX-000553
NGCFEFYHKCNNECMESVKNGTYDYPKYSEESKLNREKIDGVKLE




SMGVYQILAIYSTVASSLVLLVSLGAISFWMCSNGSLQCRICI






MRK_LZ_
ATGGAGACCCCCGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGCT
461


NIHGen6H
GCCCGACACCACCGGCGACACCATCTGCATCGGCTACCACGCC



ASS-foldon
AACAACAGCACCGACACCGTGGACACCGTGCTGGAGAAGAAC



SQ-032106
GTGACCGTGACCCACAGCGTGAACCTGGGCAGCGGCCTGAGGA



CX-000596
TGGTGACCGGCCTGAGGAACATCCCCCAGAGGGAGACCAGGGG




CCTGTTCGGCGCCATCGCCGGCTTCATCGAGGGCGGCTGGACC




GGCATGGTGGACGGCTGGTACGGCTACCACCACCAGAACGAGC




AGGGCAGCGGCTACGCCGCCGACCAGAAGAGCACCCAGAACG




CCATCAACGGCATCACCAACATGGTGAACAGCGTGATCGAGAA




GATGGGCAGCGGCGGCAGCGGCACCGACCTGGCCGAGCTGCTG




GTGCTGCTGCTGAACGAGAGGACCCTGGACTTCCACGACAGCA




ACGTGAAGAACCTGTACGAGAAGGTGAAGAGCCAGCTGAAGA




ACAACGCCAAGGAGATCGGCAACGGCTGCTTCGAGTTCTACCA




CAAGTGCAACAACGAGTGCATGGAGAGCGTGAAGAACGGCAC




CTACGACTACCCCAAGTACAGCGAGGAGAGCAAGCTGAACAGG




GAGAAGATCGACCCCGGCAGCGGCTACATCCCCGAGGCCCCCA




GGGACGGCCAGGCCTACGTGAGGAAGGACGGCGAGTGGGTGC




TGCTGAGCACCTTCCTG






MRK_LZ_

METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDTVDTVLEKNVT

462


NIHGen6H
VTHSVNLGSGLRMVTGLRNIPQRETRGLFGAIAGFIEGGWTGMVD



ASS-foldon
GWYGYHHQNEQGSGYAADQKSTQNAINGITNMVNSVIEKMGSG



SQ-032106
GSGTDLAELLVLLLNERTLDFHDSNVKNLYEKVKSQLKNNAKEIG



CX-000596
NGCFEFYHKCNNECMESVKNGTYDYPKYSEESKLNREKIDPGSGY




IPEAPRDGQAYVRKDGEWVLLSTFL










The underlined sequence for each of the amino acid sequences listed in Table 20, indicates a signal or secretory sequence, which may be substituted by an alternative sequence that achieves the same or similar function, or the signal or secretory sequence may be deleted.









TABLE 21







Additional Flu Sequences











SEQ


Name
Sequence
ID NO:





BHA10-2: HA10 version for
METPAQLLFLLLLWLPDTTGHVVKTATQGEVNVT
463


Influenza B strain, with
GVIPLTTTPTGSANKSKPYYTGEHAKATGNCPIWV



exposed hydrophobic
KTPLKLANGTKYGSAGSATQEAINKITKNLNSLSEL



residues mutated
EVKNLQRLSGASDETHNEILELDEKVDDLRADTISS




QIELAVLLSNEGIINSEDEGTGGGYIPEAPRDGQAY




VRKDGEWVLLSTFL






BHA10-3: HA10 version for
METPAQLLFLLLLWLPDTTGHVVKTATQGEVNVT
464


Influenza B strain, with
GVIPLTTTPTGSANKSKPYYTGEHAKATGNCPIWV



exposed hydrophobic
KTPLKLANGTKYGSAGSATQEAINKITKNLNSLSEL



residues mutated, with
EVKNLQRLSCASDETHNCILELDEKVDDLRADTISS



K68C/R76C/N95L
LIELAVLLSNEGIINSEDE



mutations for trimerization







NIHGen6HASS-TM: Gen6
METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDT
465


HA SS construct without
VDTVLEKNVTVTHSVNLGSGLRMVTGLRNIPQRET



foldon or ferritin, with
RGLFGAIAGFIEGGWTGMVDGWYGYHHQNEQGS



transmembrane domain,
GYAADQKSTQNAINGITNMVNSVIEKMGSGGSGT



version 1
DLAELLVLLLNERTLDFHDSNVKNLYEKVKSQLK




NNAKEIGNGCFEFYHKCNNECMESVKNGTYDYPK




YSEESKLNREKIDQGTGGILAIYSTVASSLVLLVSL




GAISFWMCSNGSLQCRICI






NIHGen6HASS-TM2: Gen6
METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDT
466


HA SS construct without
VDTVLEKNVTVTHSVNLGSGLRMVTGLRNIPQRET



foldon or ferritin, with
RGLFGAIAGFIEGGWTGMVDGWYGYHHQNEQGS



transmembrane domain,
GYAADQKSTQNAINGITNMVNSVIEKMGSGGSGT



version 2
DLAELLVLLLNERTLDFHDSNVKNLYEKVKSQLK




NNAKEIGNGCFEFYHKCNNECMESVKNGTYDYPK




YSEESKLNREKIDGVKLESMGVYQILAIYSTVASSL




VLLVSLGAISFWMCSNGSLQCRICI






H1HA10-PR8-DS-ferritin:
METPAQLLFLLLLWLPDTTGDTVDTVCEKNVTVT
467


H1HA10 from PR8 strain,
HSVNLLEDSHGSANSSLPYQNTHPTTNGESPKYVR



with additional disulfide
SAKLRMVTGLRNGSAGSATQNAINCITNKVNTVIE



mutation, without foldon
KMNIQDTATGKEFNKDEKRMENLNKKVDDGFLDI



and with ferritin fusion for
WTYNAELLVLLENERTLDAHDSQGTGGDIIKLLNE



particle formation
QVNKEMQSSNLYMSMSSWCYTHSLDGAGLFLFD




HAAEEYEHAKKLIIFLNENNVPVQLTSISAPEHKFE




GLTQIFQKAYEHEQHISESINNIVDHAIKSKDHATF




NFLQWYVAEQHEEEVLFKDILDKIELIGNENHGLY




LADQYVKGIAKSRKS






ConH1: consensus HA
MKAKLLVLLCAFTATDADTICIGYHANNSTDTVDT
468


sequence for subtype H1
VLEKNVTVTHSVNLLEDSHNGKLCKLKGIAPLQLG




KCNIAGWILGNPECESLISKRSWSYIVETPNSENGT




CYPGDFADYEELREQLSSVSSFERFEIFPKESSWPN




HNVTKGVTAACSHAGKSSFYRNLLWLTEKNGSYP




KLSKSYVNNKEKEVLVLWGVHHPSNITDQRTLYQ




NENAYVSVVSSHYNRRFTPEIAKRPKVRGQAGRIN




YYWTLLEPGDTIIFEANGNLIAPWYAFALSRGFGSG




IITSNAPMHECDTKCQTPQGAINSSLPFQNVHPVTI




GECPKYVRSTKLRMVTGLRNIPSIQSRGLFGAIAGF




IEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQ




NAINGITNKVNSVIEKMNTQFTAVGKEFNKLEKRM




ENLNKKVDDGFLDIWTYNAELLVLLENERTLDFH




DSNVKNLYEKVKSQLKNNAKEIGNGCFEFYHKCN




NECMESVKNGTYDYPKYSEESKLNREKIDGVKLES




MGVYQILAIYSTVASSLVLLVSLGAISFWMCSNGS




LQCRICI






ConH3: consensus HA
MKTIIALSYIFCLVFAQKLPGNDNSTATLCLGHHAV
469


sequence for subtype H3
PNGTLVKTITNDQIEVTNATELVQSSSTGRICDSPH




RILDGTNCTLIDALLGDPHCDGFQNKEWDLFVERS




KAYSNCYPYDVPDYASLRSLVASSGTLEFNNEGFN




WTGVTQNGGSSACKRGSDKSFFSRLNWLHKLKYK




YPALNVTMPNNDKFDKLYIWGVHHPSTDSDQTSL




YVQASGRVTVSTKRSQQTVIPNIGSRPWVRGLSSRI




SIYWTIVKPGDILLINSTGNLIAPRGYFKIRSGKSSIM




RSDAPIGTCNSECITPNGSIPNDKPFQNVNRITYGAC




PRYVKQNTLKLATGMRNVPEKQTRGIFGAIAGFIE




NGWEGMVDGWYGFRHQNSEGTGQAADLKSTQA




AIDQINGKLNRLIEKTNEKFHQIEKEFSEVEGRIQDL




EKYVEDTKIDLWSYNAELLVALENQHTIDLTDSEM




NKLFERTRKQLRENAEDMGNGCFKIYHKCDNACI




GSIRNGTYDHDVYRDEALNNRFQIKGVELKSGYK




DWILWISFAISCFLLCVVLLGFIMWACQKGNIRCNI




CI






MRK_pH1_Con: consensus
MKAILVVLLYTFATANADTLCIGYHANNSTDTVDT
470


HA sequence for pandemic
VLEKNVTVTHSVNLLEDKHNGKLCKLRGVAPLHL



H1 strains
GKCNIAGWILGNPECESLSTASSWSYIVETSSSDNG




TCYPGDFIDYEELREQLSSVSSFERFEIFPKTSSWPN




HDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYP




KLSKSYINDKGKEVLVLWGIHHPSTSADQQSLYQN




ADAYVFVGTSRYSKKFKPEIAIRPKVRDQEGRMNY




YWTLVEPGDKITFEATGNLVVPRYAFAMERNAGS




GIIISDTPVHDCNTTCQTPKGAINTSLPFQNIHPITIG




KCPKYVKSTKLRLATGLRNVPSIQSRGLFGAIAGFI




EGGWTGMVDGWYGYHHQNEQGSGYAADLKSTQ




NAIDKITNKVNSVIEKMNTQFTAVGKEFNHLEKRIE




NLNKKVDDGFLDIWTYNAELLVLLENERTLDYHD




SNVKNLYEKVRSQLKNNAKEIGNGCFEFYHKCDN




TCMESVKNGTYDYPKYSEEAKLNREEIDGVKLEST




RIYQILAIYSTVASSLVLVVSLGAISFWMCSNGSLQ




CRICI






MRK_sH1_Con: consensus
MKVKLLVLLCTFTATYADTICIGYHANNSTDTVDT
471


HA sequence for seasonal
VLEKNVTVTHSVNLLEDSHNGKLCLLKGIAPLQLG



H1 strains
NCSVAGWILGNPECELLISKESWSYIVETPNPENGT




CYPGYFADYEELREQLSSVSSFERFEIFPKESSWPN




HTVTGVSASCSHNGKSSFYRNLLWLTGKNGLYPN




LSKSYANNKEKEVLVLWGVHHPPNIGDQRALYHT




ENAYVSVVSSHYSRRFTPEIAKRPKVRDQEGRINY




YWTLLEPGDTIIFEANGNLIAPRYAFALSRGFGSGII




TSNAPMDECDAKCQTPQGAINSSLPFQNVHPVTIG




ECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGFI




EGGWTGMVDGWYGYHHQNEQGSGYAADQKSTQ




NAINGITNKVNSVIEKMNTQFTAVGKEFNKLERRM




ENLNKKVDDGFLDIWTYNAELLVLLENERTLDFH




DSNVKNLYEKVKSQLKNNAKEIGNGCFEFYHKCN




DECMESVKNGTYDYPKYSEESKLNREKIDGVKLES




MGVYQILAIYSTVASSLVLLVSLGAISFWMCSNGS




LQCRICI






Cobra_P1: consensus HA
MKARLLVLLCALAATDADTICIGYHANNSTDTVDT
472


sequence P1 for H1 subtype
VLEKNVTVTHSVNLLEDSHNGKLCKLKGIAPLQLG




KCNIAGWLLGNPECESLLSARSWSYIVETPNSENG




TCYPGDFIDYEELREQLSSVSSFERFEIFPKESSWPN




HNTTKGVTAACSHAGKSSFYRNLLWLTKKGGSYP




KLSKSYVNNKGKEVLVLWGVHHPSTSTDQQSLYQ




NENAYVSVVSSNYNRRFTPEIAERPKVRGQAGRM




NYYWTLLEPGDTIIFEATGNLIAPWYAFALSRGSGS




GIITSNASMHECNTKCQTPQGAINSSLPFQNIHPVTI




GECPKYVRSTKLRMVTGLRNIPSIQSRGLFGAIAGF




IEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQ




NAINGITNKVNSVIEKMNTQFTAVGKEFNNLEKRM




ENLNKKVDDGFLDIWTYNAELLVLLENERTLDFH




DSNVKNLYEKVKSQLRNNAKEIGNGCFEFYHKCD




NECMESVKNGTYDYPKYSEESKLNREKIDGVKLES




MGVYQILAIYSTVASSLVLLVSLGAISFWMCSNGS




LQCRICI






Cobra_X3: consensus HA
MEARLLVLLCAFAATNADTICIGYHANNSTDTVDT
473


sequence X3 for H1 subtype
VLEKNVTVTHSVNLLEDSHNGKLCRLKGIAPLQLG




NCSVAGWILGNPECESLFSKESWSYIAETPNPENGT




CYPGYFADYEELREQLSSVSSFERFEIFPKESSWPN




HTVTKGVTASCSHNGKSSFYRNLLWLTEKNGLYP




NLSKSYVNNKEKEVLVLWGVHHPSNIGDQRAIYH




TENAYVSVVSSHYSRRFTPEIAKRPKVRDQEGRIN




YYWTLLEPGDTIIFEANGNLIAPWYAFALSRGFGSG




IITSNASMDECDAKCQTPQGAINSSLPFQNVHPVTI




GECPKYVRSTKLRMVTGLRNIPSIQSRGLFGAIAGF




IEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQ




NAINGITNKVNSVIEKMNTQFTAVGKEFNKLERRM




ENLNKKVDDGFLDIWTYNAELLVLLENERTLDFH




DSNVKNLYEKVKSQLKNNAKEIGNGCFEFYHKCN




NECMESVKNGTYDYPKYSEESKLNREKIDGVKLES




MGVYQILAIYSTVASSLVLLVSLGAISFWMCSNGS




LQCRICI






ConH1_ferritin: consensus
MKAKLLVLLCAFTATDADTICIGYHANNSTDTVDT
474


HA sequence for subtype
VLEKNVTVTHSVNLLEDSHNGKLCKLKGIAPLQLG



H1, with ferritin for
KCNIAGWILGNPECESLISKRSWSYIVETPNSENGT



particle formation
CYPGDFADYEELREQLSSVSSFERFEIFPKESSWPN




HNVTKGVTAACSHAGKSSFYRNLLWLTEKNGSYP




KLSKSYVNNKEKEVLVLWGVHHPSNITDQRTLYQ




NENAYVSVVSSHYNRRFTPEIAKRPKVRGQAGRIN




YYWTLLEPGDTIIFEANGNLIAPWYAFALSRGFGSG




IITSNAPMHECDTKCQTPQGAINSSLPFQNVHPVTI




GECPKYVRSTKLRMVTGLRNIPSIQSRGLFGAIAGF




IEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQ




NAINGITNKVNSVIEKMNTQFTAVGKEFNKLEKRM




ENLNKKVDDGFLDIWTYNAELLVLLENERTLDFH




DSNVKNLYEKVKSQLKNNAKEIGNGCFEFYHKCN




NECMESVKNGTYDYPKYSEESKLNREKIDSGGDII




KLLNEQVNKEMQSSNLYMSMSSWCYTHSLDGAG




LFLFDHAAEEYEHAKKLIIFLNENNVPVQLTSISAPE




HKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKD




HATFNFLQWYVAEQHEEEVLFKDILDKIELIGNEN




HGLYLADQYVKGIAKSRKS






ConH3_ferritin: consensus
MKTIIALSYIFCLVFAQKLPGNDNSTATLCLGHHAV
475


HA sequence for subtype
PNGTLVKTITNDQIEVTNATELVQSSSTGRICDSPH



H3, with ferritin for
RILDGTNCTLIDALLGDPHCDGFQNKEWDLFVERS



particle formation
KAYSNCYPYDVPDYASLRSLVASSGTLEFNNEGFN




WTGVTQNGGSSACKRGSDKSFFSRLNWLHKLKYK




YPALNVTMPNNDKFDKLYIWGVHHPSTDSDQTSL




YVQASGRVTVSTKRSQQTVIPNIGSRPWVRGLSSRI




SIYWTIVKPGDILLINSTGNLIAPRGYFKIRSGKSSIM




RSDAPIGTCNSECITPNGSIPNDKPFQNVNRITYGAC




PRYVKQNTLKLATGMRNVPEKQTRGIFGAIAGFIE




NGWEGMVDGWYGFRHQNSEGTGQAADLKSTQA




AIDQINGKLNRLIEKTNEKFHQIEKEFSEVEGRIQDL




EKYVEDTKIDLWSYNAELLVALENQHTIDLTDSEM




NKLFERTRKQLRENAEDMGNGCFKIYHKCDNACI




GSIRNGTYDHDVYRDEALNNRFQIKSGGDIIKLLNE




QVNKEMQSSNLYMSMSSWCYTHSLDGAGLFLFD




HAAEEYEHAKKLIIFLNENNVPVQLTSISAPEHKFE




GLTQIFQKAYEHEQHISESINNIVDHAIKSKDHATF




NFLQWYVAEQHEEEVLFKDILDKIELIGNENHGLY




LADQYVKGIAKSRKS






Merck_pH1_Con_ferritin:
MKAILVVLLYTFATANADTLCIGYHANNSTDTVDT
476


consensus HA sequence for
VLEKNVTVTHSVNLLEDKHNGKLCKLRGVAPLHL



pandemic H1 strains, with
GKCNIAGWILGNPECESLSTASSWSYIVETSSSDNG



ferritin for particle
TCYPGDFIDYEELREQLSSVSSFERFEIFPKTSSWPN



formation
HDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYP




KLSKSYINDKGKEVLVLWGIHHPSTSADQQSLYQN




ADAYVFVGTSRYSKKFKPEIAIRPKVRDQEGRMNY




YWTLVEPGDKITFEATGNLVVPRYAFAMERNAGS




GIIISDTPVHDCNTTCQTPKGAINTSLPFQNIHPITIG




KCPKYVKSTKLRLATGLRNVPSIQSRGLFGAIAGFI




EGGWTGMVDGWYGYHHQNEQGSGYAADLKSTQ




NAIDKITNKVNSVIEKMNTQFTAVGKEFNHLEKRIE




NLNKKVDDGFLDIWTYNAELLVLLENERTLDYHD




SNVKNLYEKVRSQLKNNAKEIGNGCFEFYHKCDN




TCMESVKNGTYDYPKYSEEAKLNREEIDSGGDIIK




LLNEQVNKEMQSSNLYMSMSSWCYTHSLDGAGLF




LFDHAAEEYEHAKKLIIFLNENNVPVQLTSISAPEH




KFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKDH




ATFNFLQWYVAEQHEEEVLFKDILDKIELIGNENH




GLYLADQYVKGIAKSRKS






Merck_sH1_Con_ferritin:
MKVKLLVLLCTFTATYADTICIGYHANNSTDTVDT
477


consensus HA sequence for
VLEKNVTVTHSVNLLEDSHNGKLCLLKGIAPLQLG



seasonal H1 strains, with
NCSVAGWILGNPECELLISKESWSYIVETPNPENGT



ferritin for particle
CYPGYFADYEELREQLSSVSSFERFEIFPKESSWPN



formation
HTVTGVSASCSHNGKSSFYRNLLWLTGKNGLYPN




LSKSYANNKEKEVLVLWGVHHPPNIGDQRALYHT




ENAYVSVVSSHYSRRFTPEIAKRPKVRDQEGRINY




YWTLLEPGDTIIFEANGNLIAPRYAFALSRGFGSGII




TSNAPMDECDAKCQTPQGAINSSLPFQNVHPVTIG




ECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGFI




EGGWTGMVDGWYGYHHQNEQGSGYAADQKSTQ




NAINGITNKVNSVIEKMNTQFTAVGKEFNKLERRM




ENLNKKVDDGFLDIWTYNAELLVLLENERTLDFH




DSNVKNLYEKVKSQLKNNAKEIGNGCFEFYHKCN




DECMESVKNGTYDYPKYSEESKLNREKIDSGGDII




KLLNEQVNKEMQSSNLYMSMSSWCYTHSLDGAG




LFLFDHAAEEYEHAKKLIIFLNENNVPVQLTSISAPE




HKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKD




HATFNFLQWYVAEQHEEEVLFKDILDKIELIGNEN




HGLYLADQYVKGIAKSRKS






Cobra_P1_ferritin:
MKARLLVLLCALAATDADTICIGYHANNSTDTVDT
478


consensus HA sequence P1
VLEKNVTVTHSVNLLEDSHNGKLCKLKGIAPLQLG



for H1 subtype, with ferritin
KCNIAGWLLGNPECESLLSARSWSYIVETPNSENG



for particle formation
TCYPGDFIDYEELREQLSSVSSFERFEIFPKESSWPN




HNTTKGVTAACSHAGKSSFYRNLLWLTKKGGSYP




KLSKSYVNNKGKEVLVLWGVHHPSTSTDQQSLYQ




NENAYVSVVSSNYNRRFTPEIAERPKVRGQAGRM




NYYWTLLEPGDTIIFEATGNLIAPWYAFALSRGSGS




GIITSNASMHECNTKCQTPQGAINSSLPFQNIHPVTI




GECPKYVRSTKLRMVTGLRNIPSIQSRGLFGAIAGF




IEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQ




NAINGITNKVNSVIEKMNTQFTAVGKEFNNLEKRM




ENLNKKVDDGFLDIWTYNAELLVLLENERTLDFH




DSNVKNLYEKVKSQLRNNAKEIGNGCFEFYHKCD




NECMESVKNGTYDYPKYSEESKLNREKIDSGGDII




KLLNEQVNKEMQSSNLYMSMSSWCYTHSLDGAG




LFLFDHAAEEYEHAKKLIIFLNENNVPVQLTSISAPE




HKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKD




HATFNFLQWYVAEQHEEEVLFKDILDKIELIGNEN




HGLYLADQYVKGIAKSRKS






Cobra_X3_ferritin:
MEARLLVLLCAFAATNADTICIGYHANNSTDTVDT
479


consensus HA sequence X3
VLEKNVTVTHSVNLLEDSHNGKLCRLKGIAPLQLG



for H1 subtype, with ferritin
NCSVAGWILGNPECESLFSKESWSYIAETPNPENGT



for particle formation
CYPGYFADYEELREQLSSVSSFERFEIFPKESSWPN




HTVTKGVTASCSHNGKSSFYRNLLWLTEKNGLYP




NLSKSYVNNKEKEVLVLWGVHHPSNIGDQRAIYH




TENAYVSVVSSHYSRRFTPEIAKRPKVRDQEGRIN




YYWTLLEPGDTIIFEANGNLIAPWYAFALSRGFGSG




IITSNASMDECDAKCQTPQGAINSSLPFQNVHPVTI




GECPKYVRSTKLRMVTGLRNIPSIQSRGLFGAIAGF




IEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQ




NAINGITNKVNSVIEKMNTQFTAVGKEFNKLERRM




ENLNKKVDDGFLDIWTYNAELLVLLENERTLDFH




DSNVKNLYEKVKSQLKNNAKEIGNGCFEFYHKCN




NECMESVKNGTYDYPKYSEESKLNREKIDSGGDII




KLLNEQVNKEMQSSNLYMSMSSWCYTHSLDGAG




LFLFDHAAEEYEHAKKLIIFLNENNVPVQLTSISAPE




HKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKD




HATFNFLQWYVAEQHEEEVLFKDILDKIELIGNEN




HGLYLADQYVKGIAKSRKS
















TABLE 22







Signal Peptides













SEQ



Description
Sequence
ID NO:






HuIgGk signal
METPAQLLFLLLLWLPDTTG
480



peptide








IgE heavy chain
MDWTWILFLVAAATRVHS
481



epsilon -1





signal peptide








Japanese
MLGSNSGQRVVFTILLLLVA
482



encephalitis PRM
PAYS




signal sequence








VSVg protein
MKCLLYLAFLFIGVNCA
483



signal sequence








Japanese
MWLVSLAIVTACAGA
484



encephalitis JEV





signal sequence
















TABLE 23







Flagellin Nucleic Acid Sequences











SEQ


Name
Sequence
ID NO:





NT (5′
TCAAGCTTTTGGACCCTCGTACAGAAGCTAATACGACTCA
485


UTR, ORF,
CTATAGGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAA



3′ UTR)
ATATAAGAGCCACCATGGCACAAGTCATTAATACAAACA




GCCTGTCGCTGTTGACCCAGAATAACCTGAACAAATCCC




AGTCCGCACTGGGCACTGCTATCGAGCGTTTGTCTTCCGG




TCTGCGTATCAACAGCGCGAAAGACGATGCGGCAGGACA




GGCGATTGCTAACCGTTTTACCGCGAACATCAAAGGTCT




GACTCAGGCTTCCCGTAACGCTAACGACGGTATCTCCATT




GCGCAGACCACTGAAGGCGCGCTGAACGAAATCAACAAC




AACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGTCTGCG




AATGGTACTAACTCCCAGTCTGACCTCGACTCCATCCAGG




CTGAAATCACCCAGCGCCTGAACGAAATCGACCGTGTAT




CCGGCCAGACTCAGTTCAACGGCGTGAAAGTCCTGGCGC




AGGACAACACCCTGACCATCCAGGTTGGTGCCAACGACG




GTGAAACTATCGATATTGATTTAAAAGAAATCAGCTCTA




AAACACTGGGACTTGATAAGCTTAATGTCCAAGATGCCT




ACACCCCGAAAGAAACTGCTGTAACCGTTGATAAAACTA




CCTATAAAAATGGTACAGATCCTATTACAGCCCAGAGCA




ATACTGATATCCAAACTGCAATTGGCGGTGGTGCAACGG




GGGTTACTGGGGCTGATATCAAATTTAAAGATGGTCAAT




ACTATTTAGATGTTAAAGGCGGTGCTTCTGCTGGTGTTTA




TAAAGCCACTTATGATGAAACTACAAAGAAAGTTAATAT




TGATACGACTGATAAAACTCCGTTGGCAACTGCGGAAGC




TACAGCTATTCGGGGAACGGCCACTATAACCCACAACCA




AATTGCTGAAGTAACAAAAGAGGGTGTTGATACGACCAC




AGTTGCGGCTCAACTTGCTGCAGCAGGGGTTACTGGCGC




CGATAAGGACAATACTAGCCTTGTAAAACTATCGTTTGA




GGATAAAAACGGTAAGGTTATTGATGGTGGCTATGCAGT




GAAAATGGGCGACGATTTCTATGCCGCTACATATGATGA




GAAAACAGGTGCAATTACTGCTAAAACCACTACTTATAC




AGATGGTACTGGCGTTGCTCAAACTGGAGCTGTGAAATT




TGGTGGCGCAAATGGTAAATCTGAAGTTGTTACTGCTACC




GATGGTAAGACTTACTTAGCAAGCGACCTTGACAAACAT




AACTTCAGAACAGGCGGTGAGCTTAAAGAGGTTAATACA




GATAAGACTGAAAACCCACTGCAGAAAATTGATGCTGCC




TTGGCACAGGTTGATACACTTCGTTCTGACCTGGGTGCGG




TTCAGAACCGTTTCAACTCCGCTATCACCAACCTGGGCAA




TACCGTAAATAACCTGTCTTCTGCCCGTAGCCGTATCGAA




GATTCCGACTACGCAACCGAAGTCTCCAACATGTCTCGC




GCGCAGATTCTGCAGCAGGCCGGTACCTCCGTTCTGGCG




CAGGCGAACCAGGTTCCGCAAAACGTCCTCTCTTTACTGC




GTTGATAATAGGCTGGAGCCTCGGTGGCCATGCTTCTTGC




CCCTTGGGCCTCCCCCCAGCCCCTCCTCCCCTTCCTGCAC




CCGTACCCCCGTGGTCTTTGAATAAAGTCTGAGTGGGCG




GC






ORF
ATGGCACAAGTCATTAATACAAACAGCCTGTCGCTGTTG
486


Sequence,
ACCCAGAATAACCTGAACAAATCCCAGTCCGCACTGGGC



NT
ACTGCTATCGAGCGTTTGTCTTCCGGTCTGCGTATCAACA




GCGCGAAAGACGATGCGGCAGGACAGGCGATTGCTAACC




GTTTTACCGCGAACATCAAAGGTCTGACTCAGGCTTCCCG




TAACGCTAACGACGGTATCTCCATTGCGCAGACCACTGA




AGGCGCGCTGAACGAAATCAACAACAACCTGCAGCGTGT




GCGTGAACTGGCGGTTCAGTCTGCGAATGGTACTAACTC




CCAGTCTGACCTCGACTCCATCCAGGCTGAAATCACCCA




GCGCCTGAACGAAATCGACCGTGTATCCGGCCAGACTCA




GTTCAACGGCGTGAAAGTCCTGGCGCAGGACAACACCCT




GACCATCCAGGTTGGTGCCAACGACGGTGAAACTATCGA




TATTGATTTAAAAGAAATCAGCTCTAAAACACTGGGACT




TGATAAGCTTAATGTCCAAGATGCCTACACCCCGAAAGA




AACTGCTGTAACCGTTGATAAAACTACCTATAAAAATGG




TACAGATCCTATTACAGCCCAGAGCAATACTGATATCCA




AACTGCAATTGGCGGTGGTGCAACGGGGGTTACTGGGGC




TGATATCAAATTTAAAGATGGTCAATACTATTTAGATGTT




AAAGGCGGTGCTTCTGCTGGTGTTTATAAAGCCACTTATG




ATGAAACTACAAAGAAAGTTAATATTGATACGACTGATA




AAACTCCGTTGGCAACTGCGGAAGCTACAGCTATTCGGG




GAACGGCCACTATAACCCACAACCAAATTGCTGAAGTAA




CAAAAGAGGGTGTTGATACGACCACAGTTGCGGCTCAAC




TTGCTGCAGCAGGGGTTACTGGCGCCGATAAGGACAATA




CTAGCCTTGTAAAACTATCGTTTGAGGATAAAAACGGTA




AGGTTATTGATGGTGGCTATGCAGTGAAAATGGGCGACG




ATTTCTATGCCGCTACATATGATGAGAAAACAGGTGCAA




TTACTGCTAAAACCACTACTTATACAGATGGTACTGGCGT




TGCTCAAACTGGAGCTGTGAAATTTGGTGGCGCAAATGG




TAAATCTGAAGTTGTTACTGCTACCGATGGTAAGACTTAC




TTAGCAAGCGACCTTGACAAACATAACTTCAGAACAGGC




GGTGAGCTTAAAGAGGTTAATACAGATAAGACTGAAAAC




CCACTGCAGAAAATTGATGCTGCCTTGGCACAGGTTGAT




ACACTTCGTTCTGACCTGGGTGCGGTTCAGAACCGTTTCA




ACTCCGCTATCACCAACCTGGGCAATACCGTAAATAACC




TGTCTTCTGCCCGTAGCCGTATCGAAGATTCCGACTACGC




AACCGAAGTCTCCAACATGTCTCGCGCGCAGATTCTGCA




GCAGGCCGGTACCTCCGTTCTGGCGCAGGCGAACCAGGT




TCCGCAAAACGTCCTCTCTTTACTGCGT






mRNA
G*GGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAU
487


Sequence

AUAAGAGCCACCAUGGCACAAGUCAUUAAUACAAACAG




(assumes
CCUGUCGCUGUUGACCCAGAAUAACCUGAACAAAUCCC



T100 tail)
AGUCCGCACUGGGCACUGCUAUCGAGCGUUUGUCUUCC




GGUCUGCGUAUCAACAGCGCGAAAGACGAUGCGGCAGG




ACAGGCGAUUGCUAACCGUUUUACCGCGAACAUCAAAG




GUCUGACUCAGGCUUCCCGUAACGCUAACGACGGUAUC




UCCAUUGCGCAGACCACUGAAGGCGCGCUGAACGAAAU




CAACAACAACCUGCAGCGUGUGCGUGAACUGGCGGUUC




AGUCUGCGAAUGGUACUAACUCCCAGUCUGACCUCGAC




UCCAUCCAGGCUGAAAUCACCCAGCGCCUGAACGAAAU




CGACCGUGUAUCCGGCCAGACUCAGUUCAACGGCGUGA




AAGUCCUGGCGCAGGACAACACCCUGACCAUCCAGGUU




GGUGCCAACGACGGUGAAACUAUCGAUAUUGAUUUAAA




AGAAAUCAGCUCUAAAACACUGGGACUUGAUAAGCUUA




AUGUCCAAGAUGCCUACACCCCGAAAGAAACUGCUGUA




ACCGUUGAUAAAACUACCUAUAAAAAUGGUACAGAUCC




UAUUACAGCCCAGAGCAAUACUGAUAUCCAAACUGCAA




UUGGCGGUGGUGCAACGGGGGUUACUGGGGCUGAUAUC




AAAUUUAAAGAUGGUCAAUACUAUUUAGAUGUUAAAG




GCGGUGCUUCUGCUGGUGUUUAUAAAGCCACUUAUGAU




GAAACUACAAAGAAAGUUAAUAUUGAUACGACUGAUA




AAACUCCGUUGGCAACUGCGGAAGCUACAGCUAUUCGG




GGAACGGCCACUAUAACCCACAACCAAAUUGCUGAAGU




AACAAAAGAGGGUGUUGAUACGACCACAGUUGCGGCUC




AACUUGCUGCAGCAGGGGUUACUGGCGCCGAUAAGGAC




AAUACUAGCCUUGUAAAACUAUCGUUUGAGGAUAAAAA




CGGUAAGGUUAUUGAUGGUGGCUAUGCAGUGAAAAUG




GGCGACGAUUUCUAUGCCGCUACAUAUGAUGAGAAAAC




AGGUGCAAUUACUGCUAAAACCACUACUUAUACAGAUG




GUACUGGCGUUGCUCAAACUGGAGCUGUGAAAUUUGGU




GGCGCAAAUGGUAAAUCUGAAGUUGUUACUGCUACCGA




UGGUAAGACUUACUUAGCAAGCGACCUUGACAAACAUA




ACUUCAGAACAGGCGGUGAGCUUAAAGAGGUUAAUACA




GAUAAGACUGAAAACCCACUGCAGAAAAUUGAUGCUGC




CUUGGCACAGGUUGAUACACUUCGUUCUGACCUGGGUG




CGGUUCAGAACCGUUUCAACUCCGCUAUCACCAACCUG




GGCAAUACCGUAAAUAACCUGUCUUCUGCCCGUAGCCG




UAUCGAAGAUUCCGACUACGCAACCGAAGUCUCCAACA




UGUCUCGCGCGCAGAUUCUGCAGCAGGCCGGUACCUCC




GUUCUGGCGCAGGCGAACCAGGUUCCGCAAAACGUCCU




CUCUUUACUGCGUUGAUAAUAGGCUGGAGCCUCGGUGG





CCAUGCUUCUUGCCCCUUGGGCCUCCCCCCAGCCCCUCC






UCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUA






AAGUCUGAGUGGGCGGCAAAAAAAAAAAAAAAAAAAA





AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA




AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA




AAAAAAUCUAG










The first underlined sequence is representative of the 5′ UTR, which may be included in or omitted from any of the constructs listed in Table 1, or it may be modified or substituted with another 5′ UTR comprising a different sequence.


The second underlined sequence is representative of the 3′ UTR, which may be included in or omitted from any of the constructs listed in Table 1, or it may be modified or substituted with another 3′ UTR comprising a different sequence.









TABLE 24







Flagellin Amino Acid Sequences













SEQ



Name
Sequence
ID NO:






ORF
MAQVINTNSLSLLTQNNLNKSQSAL
488



Sequence,
GTAIERLSSGLRINSAKDDAAGQAI




AA
ANRFTANIKGLTQASRNANDGISIA





QTTEGALNEINNNLQRVRELAVQSA





NGTNSQSDLDSIQAEITQRLNEIDR





VSGQTQFNGVKVLAQDNTLTIQVGA





NDGETIDIDLKEISSKTLGLDKLNV





QDAYTPKETAVTVDKTTYKNGTDPI





TAQSNTDIQTAIGGGATGVTGADIK





FKDGQYYLDVKGGASAGVYKATYDE





TTKKVNIDTTDKTPLATAEATAIRG





TATITHNQIAEVTKEGVDTTTVAAQ





LAAAGVTGADKDNTSLVKLSFEDKN





GKVIDGGYAVKMGDDFYAATYDEKT





GAITAKTTTYTDGTGVAQTGAVKFG





GANGKSEVVTATDGKTYLASDLDKH





NFRTGGELKEVNTDKTENPLQKIDA





ALAQVDTLRSDLGAVQNRFNSAITN





LGNTVNNLSSARSRIEDSDYATEVS





NMSRAQILQQAGTSVLAQANQVPQN





VLSLLR







Flagellin-
MAQVINTNSLSLLTQNNLNKSQSAL
489




GS linker-

GTAIERLSSGLRINSAKDDAAGQAI





circumspor-

ANRFTANIKGLTQASRNANDGISIA





ozoite

QTTEGALNEINNNLQRVRELAVQSA





protein

NSTNSQSDLDSIQAEITQRLNEIDR





(CSP)

VSGQTQFNGVKVLAQDNTLTIQVGA





NDGETIDIDLKQINSQTLGLDTLNV





QQKYKVSDTAATVTGYADTTIALDN





STFKASATGLGGTDQKIDGDLKFDD





TTGKYYAKVTVTGGTGKDGYYEVSV





DKTNGEVTLAGGATSPLTGGLPATA





TEDVKNVQVANADLTEAKAALTAAG





VTGTASVVKMSYTDNNGKTIDGGLA





VKVGDDYYSATQNKDGSISINTTKY





TADDGTSKTALNKLGGADGKTEVVS





IGGKTYAASKAEGHNFKAQPDLAEA





AATTTENPLQKIDAALAQVDTLRSD





LGAVQNRFNSAITNLGNTVNNLTSA





RSRIEDSDYATEVSNMSRAQILQQA





GTSVLAQANQVPQNVLSLLRGGGGS






GGGGSMMAPDPNANPNANPNANPNA







NPNANPNANPNANPNANPNANPNAN







PNANPNANPNANPNANPNANPNANP







NANPNANPNANPNKNNQGNGQGHNM







PNDPNRNVDENANANNAVKNNNNEE







PSDKHIEQYLKKIKNSISTEWSPCS







VTCGNGIQVRIKPGSANKPKDELDY







ENDIEKKICKMEKCSSVFNVVNS








Flagellin-
MMAPDPNANPNANPNANPNANPNAN
490




RPVT

PNANPNANPNANPNANPNANPNANP





linker-

NANPNANPNANPNANPNANPNANPN





circumspor-

ANPNANPNKNNQGNGQGHNMPNDPN





ozoite

RNVDENANANNAVKNNNNEEPSDKH





protein

IEQYLKKIKNSISTEWSPCSVTCGN





(CSP)

GIQVRIKPGSANKPKDELDYENDIE





KKICKMEKCSSVFNVVNSRPVTMAQ






VINTNSLSLLTQNNLNKSQSALGTA







IERLSSGLRINSAKDDAAGQAIANR







FTANIKGLTQASRNANDGISIAQTT







EGALNEINNNLQRVRELAVQSANST







NSQSDLDSIQAEITQRLNEIDRVSG







QTQFNGVKVLAQDNTLTIQVGANDG







ETIDIDLKQINSQTLGLDTLNVQQK







YKVSDTAATVTGYADTTIALDNSTF







KASATGLGGTDQKIDGDLKFDDTTG







KYYAKVTVTGGTGKDGYYEVSVDKT







NGEVTLAGGATSPLTGGLPATATED







VKNVQVANADLTEAKAALTAAGVTG







TASVVKMSYTDNNGKTIDGGLAVKV







GDDYYSATQNKDGSISINTTKYTAD







DGTSKTALNKLGGADGKTEVVSIGG







KTYAASKAEGHNFKAQPDLAEAAAT







TTENPLQKIDAALAQVDTLRSDLGA







VQNRFNSAITNLGNTVNNLTSARSR







IEDSDYATEVSNMSRAQILQQAGTS







VLAQANQVPQNVLSLLR

















TABLE 25







Influenza mRNA Constructs


Influenza mRNA Sequences









Construct

SEQ


Description
ORF
ID NO:





B/Yamagata/16/
AUGAAGGCAAUAAUUGUACUACUCAUGGUAGUAACAUC
491


1988 mHA
CAACGCAGAUCGAAUCUGCACUGGGAUAACAUCUUCAAA




CUCACCUCAUGUGGUCAAAACAGCUACUCAAGGGGAAGU




UAAUGUGACUGGUGUGAUACCACUGACAACAACACCAAC




AAAAUCUCAUUUUGCAAAUCUCAAAGGAACAAAGACCA




GAGGGAAACUAUGCCCAAACUGUCUCAACUGCACAGAUC




UGGAUGUGGCCUUGGGCAGACCAAUGUGUAUGGGGACC




AUACCUUCGGCAAAAGCUUCAAUACUCCACGAAGUCAGA




CCUGUUACAUCCGGGUGCUUUCCUAUAAUGCACGACAGA




ACAAAAAUCAGACAGCUACCCAAUCUUCUCAGAGGAUAU




GAAAAUAUCAGAUUAUCAACCCAUAACGUUAUCAACGC




AGAAAGGGCACCAGGAGGACCCUACAGACUUGGAACCUC




AGGAUCUUGCCCUAACGUUACCAGUAGAAACGGAUUCU




UCGCAACAAUGGCUUGGGCUGUCCCAAGGGACAACAAAA




CAGCAACGAAUCCACUAACAGUAGAAGUACCAUACAUUU




GCACAAAAGGAGAAGACCAAAUUACUGUUUGGGGGUUC




CAUUCUGAUGACAAAACCCAAAUGAAAAACCUCUAUGG




AGACUCAAAUCCUCAAAAGUUCACCUCAUCUGCCAAUGG




AGUAACCACACAUUAUGUUUCUCAGAUUGGUGACUUCCC




AAAUCAAACAGAAGACGGAGGGCUACCACAAAGCGGCA




GAAUUGUUGUUGAUUACAUGGUGCAAAAACCUGGGAAA




ACAGGAACAAUUGUCUAUCAAAGAGGUGUUUUGUUGCC




UCAAAAGGUGUGGUGCGCAAGUGGCAGGAGCAAGGUAA




UAAAAGGGUCCUUGCCUUUAAUUGGUGAAGCAGAUUGC




CUUCACGAAAAAUACGGUGGAUUAAACAAAAGCAAGCC




UUACUACACAGGAGAACAUGCAAAAGCCAUAGGAAAUU




GCCCAAUAUGGGUGAAAACACCUUUGAAGCUUGCCAAU




GGAACCAAAUAUAGACCUCCUGCAAAACUAUUAAAGGA




AAGGGGUUUCUUCGGAGCUAUUGCUGGUUUCUUAGAGG




GAGGAUGGGAAGGAAUGAUUGCAGGUUGGCACGGAUAC




ACAUCUCAUGGAGCACAUGGAGUGGCAGUGGCAGCAGA




CCUUAAGAGCACGCAAGAAGCCAUAAACAAGAUAACAA




AAAAUCUCAAUUCUUUGAGUGAGCUAGAAGUAAAGAAU




CUUCAAAGACUAAGUGGUGCCAUGGAUGAACUCCACAAC




GAAAUACUCGAGCUGGAUGAGAAAGUGGAUGAUCUCAG




AGCUGACACAAUAAGCUCGCAAAUAGAGCUUGCAGUCU




UGCUUUCCAACGAAGGAAUAAUAAACAGUGAAGAUGAG




CAUCUAUUGGCACUUGAGAGAAAACUAAAGAAAAUGCU




GGGUCCCUCUGCUGUAGACAUAGGGAAUGGAUGCUUCG




AAACCAAACACAAGUGCAACCAGACCUGCUUAGACAGGA




UAGCUGCUGGCACCUUUAAUGCAGGAGAAUUUUCUCUU




CCCACUUUUGAUUCACUGAAUAUUACUGCUGCAUCUUUA




AAUGAUGAUGGAUUGGAUAAUCAUACUAUACUGCUCUA




CUACUCAACUGCUGCUUCUAGUUUGGCCGUAACAUUGAU




GAUAGCUAUUUUUAUUGUUUAUAUGGUCUCCAGAGACA




AUGUUUCUUGCUCCAUCUGUCUA






B/Yamagata/16/
AUGAAGGCAAUAAUUGUACUACUCAUGGUAGUAACAUC
492


1988 sHA
CAACGCAGAUCGAAUCUGCACUGGGAUAACAUCUUCAAA




CUCACCUCAUGUGGUCAAAACAGCUACUCAAGGGGAAGU




UAAUGUGACUGGUGUGAUACCACUGACAACAACACCAAC




AAAAUCUCAUUUUGCAAAUCUCAAAGGAACAAAGACCA




GAGGGAAACUAUGCCCAAACUGUCUCAACUGCACAGAUC




UGGAUGUGGCCUUGGGCAGACCAAUGUGUAUGGGGACC




AUACCUUCGGCAAAAGCUUCAAUACUCCACGAAGUCAGA




CCUGUUACAUCCGGGUGCUUUCCUAUAAUGCACGACAGA




ACAAAAAUCAGACAGCUACCCAAUCUUCUCAGAGGAUAU




GAAAAUAUCAGAUUAUCAACCCAUAACGUUAUCAACGC




AGAAAGGGCACCAGGAGGACCCUACAGACUUGGAACCUC




AGGAUCUUGCCCUAACGUUACCAGUAGAAACGGAUUCU




UCGCAACAAUGGCUUGGGCUGUCCCAAGGGACAACAAAA




CAGCAACGAAUCCACUAACAGUAGAAGUACCAUACAUUU




GCACAAAAGGAGAAGACCAAAUUACUGUUUGGGGGUUC




CAUUCUGAUGACAAAACCCAAAUGAAAAACCUCUAUGG




AGACUCAAAUCCUCAAAAGUUCACCUCAUCUGCCAAUGG




AGUAACCACACAUUAUGUUUCUCAGAUUGGUGACUUCCC




AAAUCAAACAGAAGACGGAGGGCUACCACAAAGCGGCA




GAAUUGUUGUUGAUUACAUGGUGCAAAAACCUGGGAAA




ACAGGAACAAUUGUCUAUCAAAGAGGUGUUUUGUUGCC




UCAAAAGGUGUGGUGCGCAAGUGGCAGGAGCAAGGUAA




UAAAAGGGUCCUUGCCUUUAAUUGGUGAAGCAGAUUGC




CUUCACGAAAAAUACGGUGGAUUAAACAAAAGCAAGCC




UUACUACACAGGAGAACAUGCAAAAGCCAUAGGAAAUU




GCCCAAUAUGGGUGAAAACACCUUUGAAGCUUGCCAAU




GGAACCAAAUAUAGACCUCCUGCAAAACUAUUAAAGGA




AAGGGGUUUCUUCGGAGCUAUUGCUGGUUUCUUAGAGG




GAGGAUGGGAAGGAAUGAUUGCAGGUUGGCACGGAUAC




ACAUCUCAUGGAGCACAUGGAGUGGCAGUGGCAGCAGA




CCUUAAGAGCACGCAAGAAGCCAUAAACAAGAUAACAA




AAAAUCUCAAUUCUUUGAGUGAGCUAGAAGUAAAGAAU




CUUCAAAGACUAAGUGGUGCCAUGGAUGAACUCCACAAC




GAAAUACUCGAGCUGGAUGAGAAAGUGGAUGAUCUCAG




AGCUGACACAAUAAGCUCGCAAAUAGAGCUUGCAGUCU




UGCUUUCCAACGAAGGAAUAAUAAACAGUGAAGAUGAG




CAUCUAUUGGCACUUGAGAGAAAACUAAAGAAAAUGCU




GGGUCCCUCUGCUGUAGACAUAGGGAAUGGAUGCUUCG




AAACCAAACACAAGUGCAACCAGACCUGCUUAGACAGGA




UAGCUGCUGGCACCUUUAAUGCAGGAGAAUUUUCUCUU




CCCACUUUUGAUUCACUGAAUAUUACUGCUGCAUCUUUA




AAUGAUGAUGGAUUGGAUAAUCAUACU






B/Victoria/02/
AUGAAGGCAAUAAUUGUACUACUCAUGGUAGUAACAUC
493


1987 mHA
CAAUGCAGAUCGAAUCUGCACUGGGAUAACAUCGUCAA




ACUCACCCCAUGUGGUCAAAACUGCUACUCAAGGGGAAG




UCAAUGUGACUGGUGUGAUACCACUGACAACAACACCCA




CCAAAUCUCAUUUUGCAAAUCUCAAAGGAACAAAAACCA




GAGGGAAACUAUGCCCAAAGUGUCUCAACUGCACAGAUC




UGGACGUGGCCUUGGGCAGACCAAAGUGCACGGGGACCA




UACCUUCGGCAAAAGCUUCAAUACUCCACGAAGUCAAAC




CUGUUACAUCUGGGUGCUUUCCUAUAAUGCACGACAGA




ACAAAAAUUAGACAGCUACCCAAUCUUCUCAGAGGAUAC




GAACAUAUCAGGUUAUCAACCCAUAACGUUAUCAACGCA




GAAACGGCACCAGGAGGACCCUACAAAGUUGGAACCUCA




GGGUCUUGCCCUAACGUUACCAAUGGAAACGGAUUCUUC




GCAACAAUGGCUUGGGCUGUCCCAAAAAACGACAACAAC




AAAACAGCAACAAAUCCAUUAACAGUAGAAGUACCAUA




CAUUUGUACAGAAGGAGAAGACCAAAUUACUGUUUGGG




GGUUCCACUCUGAUAACGAAGCCCAAAUGGUAAAACUCU




AUGGAGACUCAAAGCCUCAGAAGUUCACCUCAUCUGCCA




ACGGAGUGACCACACAUUACGUUUCACAGAUUGGUGGC




UUCCCAAAUCAAGCAGAAGACGGAGGGCUACCACAAAGC




GGUAGAAUUGUUGUUGAUUACAUGGUGCAAAAAUCUGG




AAAAACAGGAACAAUUACCUACCAAAGAGGUAUUUUAU




UGCCUCAAAAAGUGUGGUGCGCAAGUGGCAGGAGCAAG




GUAAUAAAAGGGUCCUUGCCUUUAAUUGGCGAAGCAGA




UUGCCUCCACGAAAAAUACGGUGGAUUAAACAAAAGCA




AGCCUUACUACACAGGGGAACAUGCAAAAGCCAUAGGA




AAUUGCCCAAUAUGGGUGAAAACACCCUUGAAGCUGGCC




AAUGGAACCAAAUAUAGACCUCCUGCAAAACUAUUAAA




GGAAAAGGGUUUCUUCGGAGCUAUUGCUGGUUUCUUAG




AAGGAGGAUGGGAAGGAAUGAUUGCAGGUUGGCACGGA




UACACAUCCCAUGGAGCACAUGGAGUAGCAGUGGCAGCA




GACCUUAAGAGUACGCAAGAAGCCAUAAACAAGAUAAC




AAAAAAUCUCAAUUCUUUGAGUGAGCUGGAAGUAAAGA




AUCUUCAAAGACUAAGCGGUGCCAUGGAUGAACUCCACA




ACAAAAUACUCGAACUGGAUGAGAAAGUGGAUGAUCUC




AGAGCUGAUACAAUAAGCUCGCAAAUAGAGCUCGCAGU




CUUGCUUUCCAACGAAGGAAUAAUAAACAGUGAAGAUG




AGCAUCUCUUGGCGCUUGAAAGAAAACUGAAGAAAAUG




CUGGGCCCCUCUGCUGUAGAGAUAGGGAAUGGAUGCUU




CGAAACCAAACACAAGUGCAACCAGACCUGCCUCGACAG




AAUAGCUGCUGGCACCUUUAAUGCAGGAGAAUUUUCUC




UCCCCACCUUUGAUUCACUAAAUAUUACUGCUGCAUCUU




UAAAUGAUGAUGGAUUGGAUAAUCAUACUAUACUGCUU




UACUACUCAACUGCUGCUUCCAGUUUGGCUGUAACAUUG




AUGAUAGCUAUCUUUAUUGUUUAUAUGGUCUCCAGAGA




CAAUGUUUCUUGCUCCAUCUGUCUA






B/Victoria/02/
AUGAAGGCAAUAAUUGUACUACUCAUGGUAGUAACAUC
494


1987 sHA
CAAUGCAGAUCGAAUCUGCACUGGGAUAACAUCGUCAA




ACUCACCCCAUGUGGUCAAAACUGCUACUCAAGGGGAAG




UCAAUGUGACUGGUGUGAUACCACUGACAACAACACCCA




CCAAAUCUCAUUUUGCAAAUCUCAAAGGAACAAAAACCA




GAGGGAAACUAUGCCCAAAGUGUCUCAACUGCACAGAUC




UGGACGUGGCCUUGGGCAGACCAAAGUGCACGGGGACCA




UACCUUCGGCAAAAGCUUCAAUACUCCACGAAGUCAAAC




CUGUUACAUCUGGGUGCUUUCCUAUAAUGCACGACAGA




ACAAAAAUUAGACAGCUACCCAAUCUUCUCAGAGGAUAC




GAACAUAUCAGGUUAUCAACCCAUAACGUUAUCAACGCA




GAAACGGCACCAGGAGGACCCUACAAAGUUGGAACCUCA




GGGUCUUGCCCUAACGUUACCAAUGGAAACGGAUUCUUC




GCAACAAUGGCUUGGGCUGUCCCAAAAAACGACAACAAC




AAAACAGCAACAAAUCCAUUAACAGUAGAAGUACCAUA




CAUUUGUACAGAAGGAGAAGACCAAAUUACUGUUUGGG




GGUUCCACUCUGAUAACGAAGCCCAAAUGGUAAAACUCU




AUGGAGACUCAAAGCCUCAGAAGUUCACCUCAUCUGCCA




ACGGAGUGACCACACAUUACGUUUCACAGAUUGGUGGC




UUCCCAAAUCAAGCAGAAGACGGAGGGCUACCACAAAGC




GGUAGAAUUGUUGUUGAUUACAUGGUGCAAAAAUCUGG




AAAAACAGGAACAAUUACCUACCAAAGAGGUAUUUUAU




UGCCUCAAAAAGUGUGGUGCGCAAGUGGCAGGAGCAAG




GUAAUAAAAGGGUCCUUGCCUUUAAUUGGCGAAGCAGA




UUGCCUCCACGAAAAAUACGGUGGAUUAAACAAAAGCA




AGCCUUACUACACAGGGGAACAUGCAAAAGCCAUAGGA




AAUUGCCCAAUAUGGGUGAAAACACCCUUGAAGCUGGCC




AAUGGAACCAAAUAUAGACCUCCUGCAAAACUAUUAAA




GGAAAAGGGUUUCUUCGGAGCUAUUGCUGGUUUCUUAG




AAGGAGGAUGGGAAGGAAUGAUUGCAGGUUGGCACGGA




UACACAUCCCAUGGAGCACAUGGAGUAGCAGUGGCAGCA




GACCUUAAGAGUACGCAAGAAGCCAUAAACAAGAUAAC




AAAAAAUCUCAAUUCUUUGAGUGAGCUGGAAGUAAAGA




AUCUUCAAAGACUAAGCGGUGCCAUGGAUGAACUCCACA




ACAAAAUACUCGAACUGGAUGAGAAAGUGGAUGAUCUC




AGAGCUGAUACAAUAAGCUCGCAAAUAGAGCUCGCAGU




CUUGCUUUCCAACGAAGGAAUAAUAAACAGUGAAGAUG




AGCAUCUCUUGGCGCUUGAAAGAAAACUGAAGAAAAUG




CUGGGCCCCUCUGCUGUAGAGAUAGGGAAUGGAUGCUU




CGAAACCAAACACAAGUGCAACCAGACCUGCCUCGACAG




AAUAGCUGCUGGCACCUUUAAUGCAGGAGAAUUUUCUC




UCCCCACCUUUGAUUCACUAAAUAUUACUGCUGCAUCUU




UAAAUGAUGAUGGAUUGGAUAAUCAUACU






B/Brisbane/60/
AUGAAGGCAAUAAUUGUACUACUCAUGGUAGUAACAUC
495


2008 mHA
CAAUGCAGAUCGAAUCUGCACUGGGAUAACAUCGUCAA




ACUCACCACAUGUCGUCAAAACUGCUACUCAAGGGGAGG




UCAAUGUGACUGGUGUAAUACCACUGACAACAACACCCA




CCAAAUCUCAUUUUGCAAAUCUCAAAGGAACAGAAACCA




GGGGGAAACUAUGCCCAAAAUGCCUCAACUGCACAGAUC




UGGACGUAGCCUUGGGCAGACCAAAAUGCACGGGGAAA




AUACCCUCGGCAAGAGUUUCAAUACUCCAUGAAGUCAGA




CCUGUUACAUCUGGGUGCUUUCCUAUAAUGCACGACAGA




ACAAAAAUUAGACAGCUGCCUAACCUUCUCCGAGGAUAC




GAACAUAUCAGGUUAUCAACCCAUAACGUUAUCAAUGC




AGAAAAUGCACCAGGAGGACCCUACAAAAUUGGAACCUC




AGGGUCUUGCCCUAACAUUACCAAUGGAAACGGAUUUU




UCGCAACAAUGGCUUGGGCCGUCCCAAAAAACGACAAAA




ACAAAACAGCAACAAAUCCAUUAACAAUAGAAGUACCA




UACAUUUGUACAGAAGGAGAAGACCAAAUUACCGUUUG




GGGGUUCCACUCUGACGACGAGACCCAAAUGGCAAAGCU




CUAUGGGGACUCAAAGCCCCAGAAGUUCACCUCAUCUGC




CAACGGAGUGACCACACAUUACGUUUCACAGAUUGGUG




GCUUCCCAAAUCAAACAGAAGACGGAGGACUACCACAAA




GUGGUAGAAUUGUUGUUGAUUACAUGGUGCAAAAAUCU




GGGAAAACAGGAACAAUUACCUAUCAAAGGGGUAUUUU




AUUGCCUCAAAAGGUGUGGUGCGCAAGUGGCAGGAGCA




AGGUAAUAAAAGGAUCCUUGCCUUUAAUUGGAGAAGCA




GAUUGCCUCCACGAAAAAUACGGUGGAUUAAACAAAAG




CAAGCCUUACUACACAGGGGAACAUGCAAAGGCCAUAGG




AAAUUGCCCAAUAUGGGUGAAAACACCCUUGAAGCUGG




CCAAUGGAACCAAAUAUAGACCUCCUGCAAAACUAUUAA




AGGAAAGGGGUUUCUUCGGAGCUAUUGCUGGUUUCUUA




GAAGGAGGAUGGGAAGGAAUGAUUGCAGGUUGGCACGG




AUACACAUCCCAUGGGGCACAUGGAGUAGCGGUGGCAGC




AGACCUUAAGAGCACUCAAGAGGCCAUAAACAAGAUAA




CAAAAAAUCUCAACUCUUUGAGUGAGCUGGAAGUAAAG




AAUCUUCAAAGACUAAGCGGUGCCAUGGAUGAACUCCAC




AACGAAAUACUAGAACUAGAUGAGAAAGUGGAUGAUCU




CAGAGCUGAUACAAUAAGCUCACAAAUAGAACUCGCAG




UCCUGCUUUCCAAUGAAGGAAUAAUAAACAGUGAAGAU




GAACAUCUCUUGGCGCUUGAAAGAAAGCUGAAGAAAAU




GCUGGGCCCCUCUGCUGUAGAGAUAGGGAAUGGAUGCU




UUGAAACCAAACACAAGUGCAACCAGACCUGUCUCGACA




GAAUAGCUGCUGGUACCUUUGAUGCAGGAGAAUUUUCU




CUCCCCACCUUUGAUUCACUGAAUAUUACUGCUGCAUCU




UUAAAUGACGAUGGAUUGGAUAAUCAUACUAUACUGCU




UUACUACUCAACUGCUGCCUCCAGUUUGGCUGUAACACU




GAUGAUAGCUAUCUUUGUUGUUUAUAUGGUCUCCAGAG




ACAAUGUUUCUUGCUCCAUCUGUCUA






B/Brisbane/60/
AUGAAGGCAAUAAUUGUACUACUCAUGGUAGUAACAUC
496


2008 sHA
CAAUGCAGAUCGAAUCUGCACUGGGAUAACAUCGUCAA




ACUCACCACAUGUCGUCAAAACUGCUACUCAAGGGGAGG




UCAAUGUGACUGGUGUAAUACCACUGACAACAACACCCA




CCAAAUCUCAUUUUGCAAAUCUCAAAGGAACAGAAACCA




GGGGGAAACUAUGCCCAAAAUGCCUCAACUGCACAGAUC




UGGACGUAGCCUUGGGCAGACCAAAAUGCACGGGGAAA




AUACCCUCGGCAAGAGUUUCAAUACUCCAUGAAGUCAGA




CCUGUUACAUCUGGGUGCUUUCCUAUAAUGCACGACAGA




ACAAAAAUUAGACAGCUGCCUAACCUUCUCCGAGGAUAC




GAACAUAUCAGGUUAUCAACCCAUAACGUUAUCAAUGC




AGAAAAUGCACCAGGAGGACCCUACAAAAUUGGAACCUC




AGGGUCUUGCCCUAACAUUACCAAUGGAAACGGAUUUU




UCGCAACAAUGGCUUGGGCCGUCCCAAAAAACGACAAAA




ACAAAACAGCAACAAAUCCAUUAACAAUAGAAGUACCA




UACAUUUGUACAGAAGGAGAAGACCAAAUUACCGUUUG




GGGGUUCCACUCUGACGACGAGACCCAAAUGGCAAAGCU




CUAUGGGGACUCAAAGCCCCAGAAGUUCACCUCAUCUGC




CAACGGAGUGACCACACAUUACGUUUCACAGAUUGGUG




GCUUCCCAAAUCAAACAGAAGACGGAGGACUACCACAAA




GUGGUAGAAUUGUUGUUGAUUACAUGGUGCAAAAAUCU




GGGAAAACAGGAACAAUUACCUAUCAAAGGGGUAUUUU




AUUGCCUCAAAAGGUGUGGUGCGCAAGUGGCAGGAGCA




AGGUAAUAAAAGGAUCCUUGCCUUUAAUUGGAGAAGCA




GAUUGCCUCCACGAAAAAUACGGUGGAUUAAACAAAAG




CAAGCCUUACUACACAGGGGAACAUGCAAAGGCCAUAGG




AAAUUGCCCAAUAUGGGUGAAAACACCCUUGAAGCUGG




CCAAUGGAACCAAAUAUAGACCUCCUGCAAAACUAUUAA




AGGAAAGGGGUUUCUUCGGAGCUAUUGCUGGUUUCUUA




GAAGGAGGAUGGGAAGGAAUGAUUGCAGGUUGGCACGG




AUACACAUCCCAUGGGGCACAUGGAGUAGCGGUGGCAGC




AGACCUUAAGAGCACUCAAGAGGCCAUAAACAAGAUAA




CAAAAAAUCUCAACUCUUUGAGUGAGCUGGAAGUAAAG




AAUCUUCAAAGACUAAGCGGUGCCAUGGAUGAACUCCAC




AACGAAAUACUAGAACUAGAUGAGAAAGUGGAUGAUCU




CAGAGCUGAUACAAUAAGCUCACAAAUAGAACUCGCAG




UCCUGCUUUCCAAUGAAGGAAUAAUAAACAGUGAAGAU




GAACAUCUCUUGGCGCUUGAAAGAAAGCUGAAGAAAAU




GCUGGGCCCCUCUGCUGUAGAGAUAGGGAAUGGAUGCU




UUGAAACCAAACACAAGUGCAACCAGACCUGUCUCGACA




GAAUAGCUGCUGGUACCUUUGAUGCAGGAGAAUUUUCU




CUCCCCACCUUUGAUUCACUGAAUAUUACUGCUGCAUCU




UUAAAUGACGAUGGAUUGGAUAAUCAUACU






B/Phuket/3073/
AUGAAGGCAAUAAUUGUACUACUCAUGGUAGUAACAUC
497


2013 mHA
CAAUGCAGAUCGAAUCUGCACUGGGAUAACAUCUUCAA




ACUCACCUCAUGUGGUCAAAACAGCUACUCAAGGGGAGG




UCAAUGUGACUGGCGUGAUACCACUGACAACAACACCAA




CAAAAUCUUAUUUUGCAAAUCUCAAAGGAACAAGGACC




AGAGGGAAACUAUGCCCGGACUGUCUCAACUGUACAGA




UCUGGAUGUGGCCUUGGGCAGGCCAAUGUGUGUGGGGA




CCACACCUUCUGCUAAAGCUUCAAUACUCCACGAGGUCA




GACCUGUUACAUCCGGGUGCUUUCCUAUAAUGCACGACA




GAACAAAAAUCAGGCAACUACCCAAUCUUCUCAGAGGAU




AUGAAAAGAUCAGGUUAUCAACCCAAAACGUUAUCGAU




GCAGAAAAAGCACCAGGAGGACCCUACAGACUUGGAACC




UCAGGAUCUUGCCCUAACGCUACCAGUAAAAUCGGAUUU




UUCGCAACAAUGGCUUGGGCUGUCCCAAAGGACAACUAC




AAAAAUGCAACGAACCCACUAACAGUAGAAGUACCAUAC




AUUUGUACAGAAGGGGAAGACCAAAUUACUGUUUGGGG




GUUCCAUUCAGACAACAAAACCCAAAUGAAGAGCCUCUA




UGGAGACUCAAAUCCUCAAAAGUUCACCUCAUCUGCUAA




UGGAGUAACCACACAUUAUGUUUCUCAGAUUGGCGACU




UCCCAGAUCAAACAGAAGACGGAGGACUACCACAAAGCG




GCAGAAUUGUUGUUGAUUACAUGAUGCAAAAACCUGGG




AAAACAGGAACAAUUGUCUAUCAAAGAGGUGUUUUGUU




GCCUCAAAAGGUGUGGUGCGCGAGUGGCAGGAGCAAAG




UAAUAAAAGGGUCAUUGCCUUUAAUUGGUGAAGCAGAU




UGCCUUCAUGAAAAAUACGGUGGAUUAAACAAAAGCAA




GCCUUACUACACAGGAGAACAUGCAAAAGCCAUAGGAA




AUUGCCCAAUAUGGGUAAAAACACCUUUGAAGCUUGCC




AAUGGAACCAAAUAUAGACCUCCUGCAAAACUAUUGAA




GGAAAGGGGUUUCUUCGGAGCUAUUGCUGGUUUCCUAG




AAGGAGGAUGGGAAGGAAUGAUUGCAGGUUGGCACGGA




UACACAUCUCACGGAGCACAUGGAGUGGCAGUGGCGGCA




GACCUUAAGAGUACACAAGAAGCUAUAAAUAAGAUAAC




AAAAAAUCUCAAUUCUUUGAGUGAGCUAGAAGUAAAGA




ACCUUCAAAGACUAAGUGGUGCCAUGGAUGAACUCCACA




ACGAAAUACUCGAGCUGGAUGAGAAAGUGGAUGAUCUC




AGAGCUGACACUAUAAGCUCACAAAUAGAACUUGCAGU




CUUGCUUUCCAACGAAGGAAUAAUAAACAGUGAAGACG




AGCAUCUAUUGGCACUUGAGAGAAAACUAAAGAAAAUG




CUGGGUCCCUCUGCUGUAGACAUAGGAAACGGAUGCUUC




GAAACCAAACACAAAUGCAACCAGACCUGCUUAGACAGG




AUAGCUGCUGGCACCUUUGAUGCAGGAGAAUUUUCUCU




CCCCACUUUUGAUUCAUUGAACAUUACUGCUGCAUCUUU




AAAUGAUGAUGGAUUGGAUAACCAUACUAUACUGCUCU




AUUACUCAACUGCUGCUUCUAGUUUGGCUGUAACAUUA




AUGCUAGCUAUUUUUAUUGUUUAUAUGGUCUCCAGAGA




CAACGUUUCAUGCUCCAUCUGUCUA






H1
AGCAAAAGCAGGGGAAAAUAAAAACAACCAAAAUGAAG
498



GCAAACCUACUGGUCCUGUUAUGUGCACUUGCAGCUGCA




GAUGCAGACACAAUAUGUAUAGGCUACCAUGCGAACAA




UUCAACCGACACUGUUGACACAGUGCUCGAGAAGAAUG




UGACAGUGACACACUCUGUUAACCUGCUCGAAGACAGCC




ACAACGGAAAACUAUGUAGAUUAAAAGGAAUAGCCCCA




CUACAAUUGGGGAAAUGUAACAUCGCCGGAUGGCUCUU




GGGAAACCCAGAAUGCGACCCACUGCUUCCAGUGAGAUC




AUGGUCCUACAUUGUAGAAACACCAAACUCUGAGAAUG




GAAUAUGUUAUCCAGGAGAUUUCAUCGACUAUGAGGAG




CUGAGGGAGCAAUUGAGCUCAGUGUCAUCAUUCGAAAG




AUUCGAAAUAUUUCCCAAAGAAAGCUCAUGGCCCAACCA




CAACACAACCAAAGGAGUAACGGCAGCAUGCUCCCAUGC




GGGGAAAAGCAGUUUUUACAGAAAUUUGCUAUGGCUGA




CGGAGAAGGAGGGCUCAUACCCAAAGCUGAAAAAUUCU




UAUGUGAACAAGAAAGGGAAAGAAGUCCUUGUACUGUG




GGGUAUUCAUCACCCGUCUAACAGUAAGGAUCAACAGA




AUAUCUAUCAGAAUGAAAAUGCUUAUGUCUCUGUAGUG




ACUUCAAAUUAUAACAGGAGAUUUACCCCGGAAAUAGC




AGAAAGACCCAAAGUAAGAGAUCAAGCUGGGAGGAUGA




ACUAUUACUGGACCUUGCUAAAACCCGGAGACACAAUAA




UAUUUGAGGCAAAUGGAAAUCUAAUAGCACCAAGGU




AUGCUUUCGCACUGAGUAGAGGCUUUGGGUCCGGCAUC




AUCACCUCAAACGCAUCAAUGCAUGAGUGUAACACGAAG




UGUCAAACACCCCUGGGAGCUAUAAACAGCAGUCUCCCU




UUCCAGAAUAUACACCCAGUCACAAUAGGAGAGUGCCCA




AAAUACGUCAGGAGUGCCAAAUUGAGGAUGGUUACAGG




ACUAAGGAACAUUCCGUCCAUUCAAUCCAGAGGUCUAUU




UGGAGCCAUUGCCGGUUUUAUUGAAGGGGGAUGGACUG




GAAUGAUAGAUGGAUGGUACGGUUAUCAUCAUCAGAAU




GAACAGGGAUCAGGCUAUGCAGCGGAUCAAAAAAGCAC




ACAAAAUGCCAUUAACGGGAUUACAAACAAGGUGAACU




CUGUUAUCGAGAAAAUGAACAUUCAAUUCACAGCUGUG




GGUAAAGAAUUCAACAAAUUAGAAAAAAGGAUGGAAAA




UUUAAAUAAAAAAGUUGAUGAUGGAUUUCUGGACAUUU




GGACAUAUAAUGCAGAAUUGUUAGUUCUACUGGAAAAU




GAAAGGACUCUGGAUUUCCAUGACUCAAAUGUGAAGAA




UCUGUAUGAGAAAGUAAAAAGCCAAUUAAAGAAUAAUG




CCAAAGAAAUCGGAAAUGGAUGUUUUGAGUUCUACCAC




AAGUGUGACAAUGAAUGCAUGGAAAGUGUAAGAAAUGG




GACUUAUGAUUAUCCCAAAUAUUCAGAAGAGUCAAAGU




UGAACAGGGAAAAGGUAGAUGGAGUGAAAUUGGAAUCA




AUGGGGAUCUAUCAGAUUCUGGCGAUCUACUCAACUGU




CGCCAGUUCACUGGUGCUUUUGGUCUCCCUGGGGGCAAU




CAGUUUCUGGAUGUGUUCUAAUGGAUCUUUGCAGUGCA




GAAUAUGCAUCUGAGAUUAGAAUUUCAGAAAUAUGAGG




AAAAACACCCUUGUUUCUACU






H7
AGCGAAAGCAGGGGAUACAAAAUGAACACUCAAAUCCU
499



GGUAUUCGCUCUGAUUGCGAUCAUUCCAACAAAUGCAG




ACAAAAUCUGCCUCGGACAUCAUGCCGUGUCAAACGGAA




CCAAAGUAAACACAUUAACUGAAAGAGGAGUGGAAGUC




GUCAAUGCAACUGAAACAGUGGAACGAACAAACAUCCCC




AGGAUCUGCUCAAAAGGGAAAAGGACAGUUGACCUCGG




UCAAUGUGGACUCCUGGGGACAAUCACUGGACCACCUCA




AUGUGACCAAUUCCUAGAAUUUUCAGCCGAUUUAAUUA




UUGAGAGGCGAGAAGGAAGUGAUGUCUGUUAUCCUGGG




AAAUUCGUGAAUGAAGAAGCUCUGAGGCAAAUUCUCAG




AGAAUCAGGCGGAAUUGACAAGGAAGCAAUGGGAUUCA




CAUACAGUGGAAUAAGAACUAAUGGAGCAACCAGUGCA




UGUAGGAGAUCAGGAUCUUCAUUCUAUGCAGAAAUGAA




AUGGCUCCUGUCAAACACAGAUGAUGCUGCAUUCCCGCA




GAUGACUAAGUCAUAUAAAAAUACAAGAAAAAGCCCAG




CUCUAAUAGUAUGGGGGAUCCAUCAUUCCGUAUCAACU




GCAGAGCAAACCAAGCUAUAUGGGAGUGGAAACAAACU




GGUGACAGUUGGGAGUUCUAAUUAUCAACAAUCUUUUG




UACCGAGUCCAGGAGCGAGACCACAAGUUAAUGGUCUA




UCUGGAAGAAUUGACUUUCAUUGGCUAAUGCUAAAUCC




CAAUGAUACAGUCACUUUCAGUUUCAAUGGGGCUUUCA




UAGCUCCAGACCGUGCAAGCUUCCUGAGAGGAAAAUCUA




UGGGAAUCCAGAGUGGAGUACAGGUUGAUGCCAAUUGU




GAAGGGGACUGCUAUCAUAGUGGAGGGACAAUAAUAAG




UAACUUGCCAUUUCAGAACAUAGAUAGCAGGGCAGUUG




GAAAAUGUCCGAGAUAUGUUAAGCAAAGGAGUCUGCUG




CUAGCAACAGGGAUGAAGAAUGUUCCUGAGAUUCCAAA




GGGAAGAGGCCUAUUUGGUGCUAUAGCGGGUUUCAUUG




AAAAUGGAUGGGAAGGCCUAAUUGAUGGUUGGUAUGGU




UUCAGACACCAGAAUGCACAGGGAGAGGGAACUGCUGC




AGAUUACAAAAGCACUCAAUCGGCAAUUGAUCAAAUAA




CAGGAAAAUUAAACCGGCUUAUAGAAAAAACCAACCAA




CAAUUUGAGUUGAUAGACAAUGAAUUCAAUGAGGUAGA




GAAGCAAAUCGGUAAUGUGAUAAAUUGGACCAGAGAUU




CUAUAACAGAAGUGUGGUCAUACAAUGCUGAACUCUUG




GUAGCAAUGGAGAACCAGCAUACAAUUGAUCUGGCUGA




UUCAGAAAUGGACAAACUGUACGAACGAGUGAAAAGAC




AGCUGAGAGAGAAUGCUGAAGAAGAUGGCACUGGUUGC




UUUGAAAUAUUUCACAAGUGUGAUGAUGACUGUAUGGC




CAGUAUUAGAAAUAACACCUAUGAUCACAGCAAAUACA




GGGAAGAGGCAAUGCAAAAUAGAAUACAGAUUGACCCA




GUCAAACUAAGCAGCGGCUACAAAGAUGUGAUACUUUG




GUUUAGCUUCGGGGCAUCAUGUUUCAUACUUCUAGCCA




UUGUAAUGGGCCUUGUCUUCAUAUGUGUAAAGAAUGGA




AACAUGCGGUGCACUAUUUGUAUAUAAGUUUGGAAAAA




AACACCCUUGUUUCUAC






H10
AUGUACAAAAUAGUAGUGAUAAUCGCGCUCCUUGGAGC
500



UGUGAAAGGUCUUGAUAAAAUCUGUCUAGGACAUCAUG




CAGUGGCUAAUGGGACCAUCGUAAAGACUCUCACAAACG




AACAGGAAGAGGUAACCAACGCUACUGAAACAGUGGAG




AGUACAGGCAUAAACAGAUUAUGUAUGAAAGGAAGAAA




ACAUAAAGACCUGGGCAACUGCCAUCCAAUAGGGAUGCU




AAUAGGGACUCCAGCUUGUGAUCUGCACCUUACAGGGA




UGUGGGACACUCUCAUUGAACGAGAGAAUGCUAUUGCU




UACUGCUACCCUGGAGCUACUGUAAAUGUAGAAGCACU




AAGGCAGAAGAUAAUGGAGAGUGGAGGGAUCAACAAGA




UAAGCACUGGCUUCACUUAUGGAUCUUCCAUAAACUCGG




CCGGGACCACUAGAGCGUGCAUGAGGAAUGGAGGGAAU




AGCUUUUAUGCAGAGCUUAAGUGGCUGGUAUCAAAGAG




CAAAGGACAAAACUUCCCUCAGACCACGAACACUUACAG




AAAUACAGACACGGCUGAACACCUCAUAAUGUGGGGAA




UUCAUCACCCUUCUAGCACUCAAGAGAAGAAUGAUCUAU




AUGGAACACAAUCACUGUCCAUAUCAGUCGGGAGUUCCA




CUUACCGGAACAAUUUUGUUCCGGUUGUUGGAGCAAGA




CCUCAGGUCAAUGGACAAAGUGGCAGAAUUGAUUUUCA




CUGGACACUAGUACAGCCAGGUGACAACAUCACCUUCUC




ACACAAUGGGGGCCUGAUAGCACCGAGCCGAGUUAGCAA




AUUAAUUGGGAGGGGAUUGGGAAUCCAAUCAGACGCAC




CAAUAGACAAUAAUUGUGAGUCCAAAUGUUUUUGGAGA




GGGGGUUCUAUAAAUACAAGGCUUCCCUUUCAAAAUUU




GUCACCAAGAACAGUGGGUCAGUGUCCUAAAUAUGUGA




ACAGAAGAAGCUUGAUGCUUGCAACAGGAAUGAGAAAC




GUACCAGAACUAAUACAAGGGAGAGGUCUAUUUGGUGC




AAUAGCAGGGUUUUUAGAGAAUGGGUGGGAAGGAAUGG




UAGAUGGCUGGUAUGGUUUCAGACAUCAAAAUGCUCAG




GGCACAGGCCAGGCCGCUGAUUACAAGAGUACUCAGGCA




GCUAUUGAUCAAAUCACUGGGAAACUGAAUAGACUUGU




UGAAAAAACCAAUACUGAGUUCGAGUCAAUAGAAUCUG




AGUUCAGUGAGAUCGAACACCAAAUCGGUAACGUCAUC




AAUUGGACUAAGGAUUCAAUAACCGACAUUUGGACUUA




UCAGGCUGAGCUGUUGGUGGCAAUGGAGAACCAGCAUA




CAAUCGACAUGGCUGACUCAGAGAUGUUGAAUCUAUAU




GAAAGAGUGAGGAAACAACUAAGGCAGAAUGCAGAAGA




AGAUGGGAAAGGAUGUUUUGAGAUAUAUCAUGCUUGUG




AUGAUUCAUGCAUGGAGAGCAUAAGAAACAACACCUAU




GACCAUUCACAGUACAGAGAGGAAGCUCUUUUGAACAG




AUUGAAUAUCAACCCAGUGACACUCUCUUCUGGAUAUA




AAGACAUCAUUCUCUGGUUUAGCUUCGGGGCAUCAUGU




UUUGUUCUUCUAGCCGUUGUCAUGGGUCUUUUCUUUUU




CUGUCUGAAGAAUGGAAACAUGCGAUGCACAAUCUGUA




UUUAG






MRK_LZ_NP-
AUGGCCAGCCAGGGCACCAAGAGAAGCUACGAGCAGAUG
501


H3N2
GAGACCGACGGCGAGAGACAGAACGCCACCGAGAUCAGA



SQ-031687
GCCAGCGUGGGCAAGAUGAUCGACGGCAUCGGCAGAUUC



CX-003145
UACAUCCAGAUGUGCACCGAGCUCAAGCUGAGCGACUAC




GAGGGCAGACUGAUCCAGAACAGCCUGACCAUCGAAAGA




AUGGUUCUGAGCGCCUUCGACGAGAGAAGAAACAGAUA




CCUGGAGGAGCACCCCAGCGCCGGCAAGGACCCCAAGAA




GACCGGCGGCCCCAUCUACAAGAGAGUGGACGGCAGAUG




GAUGAGAGAGCUGGUGCUGUACGACAAGGAGGAGAUCA




GAAGAAUCUGGAGACAGGCCAACAACGGCGACGACGCCA




CCGCCGGCCUGACCCACAUGAUGAUCUGGCACAGCAACC




UGAACGACACCACCUACCAGAGAACCAGAGCCCUGGUGA




GAACCGGCAUGGACCCCAGAAUGUGCAGCUUAAUGCAGG




GCAGCACCCUGCCCAGAAGAUCCGGCGCCGCUGGUGCCG




CCGUCAAGGGCAUCGGCACCAUGGUGAUGGAGCUGAUCC




GCAUGAUCAAGCGCGGCAUCAACGACAGAAACUUCUGGA




GAGGCGAAAACGGCAGAAAGACCAGAAGCGCCUACGAG




AGAAUGUGCAACAUCCUGAAGGGCAAGUUCCAGACCGCC




GCCCAAAGAGCCAUGAUGGACCAGGUGAGAGAGAGCAG




AAACCCCGGCAACGCCGAGAUCGAAGACCUGAUCUUCAG




CGCCAGAUCGGCCCUGAUCCUGAGAGGCAGCGUGGCCCA




CAAGAGCUGCCUGCCCGCCUGCGUGUAUGGCCCCGCCGU




GAGCAGCGGCUACAACUUCGAGAAGGAGGGCUACAGCCU




GGUGGGCAUCGACCCCUUCAAGCUGCUGCAGAACUCUCA




GGUGUAUAGCCUGAUCAGACCCAACGAGAACCCCGCCCA




CAAGAGCCAGCUGGUGUGGAUGGCCUGCCACAGCGCCGC




CUUCGAGGACCUGAGACUGCUGAGCUUCAUCAGAGGUAC




CAAGGUGUCCCCCAGAGGCAAGCUGAGCACCAGAGGUGU




GCAGAUCGCCAGCAAUGAGAACAUGGACAAUAUGGAGA




GCAGCACCCUGGAGCUAAGAAGCAGGUACUGGGCCAUCC




GGACCAGAAGCGGCGGCAAUACCAACCAGCAGAGAGCCA




GCGCCGGCCAGAUCAGCGUGCAGCCCACCUUCAGCGUGC




AGAGAAACCUGCCCUUUGAGAAGAGCACCGUGAUGGCCG




CCUUCACCGGCAACACCGAGGGCAGAACCAGCGACAUGA




GAGCCGAGAUCAUCAGAAUGAUGGAGGGCGCCAAGCCCG




AGGAGGUGAGCUUUAGAGGCAGAGGCGUGUUCGAGCUG




AGCGACGAGAAGGCCACCAACCCAAUUGUGCCCAGCUUC




GACAUGUCGAACGAGGGCAGCUACUUCUUCGGCGACAAC




GCCGAGGAGUACGACAAC






MRK_LZ_NIHG
AUGGAGACCCCCGCCCAGCUGCUGUUCCUGCUGCUGCUG
502


en6HASS-TM2
UGGCUGCCCGACACCACCGGCGACACCAUCUGCAUCGGC



SQ-034074
UACCACGCCAACAACAGCACCGACACCGUGGACACCGUG



CX-000553
CUGGAGAAGAACGUGACCGUGACCCACAGCGUGAACCUG




GGCAGCGGCCUGAGGAUGGUGACCGGCCUGAGGAACAUC




CCCCAGAGGGAGACCAGGGGCCUGUUCGGCGCCAUCGCC




GGCUUCAUCGAGGGCGGCUGGACCGGCAUGGUGGACGGC




UGGUACGGCUACCACCACCAGAACGAGCAGGGCAGCGGC




UACGCCGCCGACCAGAAGAGCACCCAGAACGCCAUCAAC




GGCAUCACCAACAUGGUGAACAGCGUGAUCGAGAAGAU




GGGCAGCGGCGGCAGCGGCACCGACCUGGCCGAGCUGCU




GGUGCUGCUGCUGAACGAGAGGACCCUGGACUUCCACGA




CAGCAACGUGAAGAACCUGUACGAGAAGGUGAAGAGCC




AGCUGAAGAACAACGCCAAGGAGAUCGGCAACGGCUGCU




UCGAGUUCUACCACAAGUGCAACAACGAGUGCAUGGAG




AGCGUGAAGAACGGCACCUACGACUACCCCAAGUACAGC




GAGGAGAGCAAGCUGAACAGGGAGAAGAUCGACGGAGU




GAAAUUGGAAUCAAUGGGGGUCUAUCAGAUCCUGGCCA




UCUACAGCACCGUGGCCAGCAGCCUGGUGCUGCUGGUGA




GCCUGGGCGCCAUCAGCUUCUGGAUGUGCAGCAACGGCA




GCCUGCAGUGCAGAAUCUGCAUC






MRK_LZ_NIHG
AUGGAGACCCCCGCCCAGCUGCUGUUCCUGCUGCUGCUG
503


en6HASS-foldon
UGGCUGCCCGACACCACCGGCGACACCAUCUGCAUCGGC



SQ-032106
UACCACGCCAACAACAGCACCGACACCGUGGACACCGUG



CX-000596
CUGGAGAAGAACGUGACCGUGACCCACAGCGUGAACCUG




GGCAGCGGCCUGAGGAUGGUGACCGGCCUGAGGAACAUC




CCCCAGAGGGAGACCAGGGGCCUGUUCGGCGCCAUCGCC




GGCUUCAUCGAGGGCGGCUGGACCGGCAUGGUGGACGGC




UGGUACGGCUACCACCACCAGAACGAGCAGGGCAGCGGC




UACGCCGCCGACCAGAAGAGCACCCAGAACGCCAUCAAC




GGCAUCACCAACAUGGUGAACAGCGUGAUCGAGAAGAU




GGGCAGCGGCGGCAGCGGCACCGACCUGGCCGAGCUGCU




GGUGCUGCUGCUGAACGAGAGGACCCUGGACUUCCACGA




CAGCAACGUGAAGAACCUGUACGAGAAGGUGAAGAGCC




AGCUGAAGAACAACGCCAAGGAGAUCGGCAACGGCUGCU




UCGAGUUCUACCACAAGUGCAACAACGAGUGCAUGGAG




AGCGUGAAGAACGGCACCUACGACUACCCCAAGUACAGC




GAGGAGAGCAAGCUGAACAGGGAGAAGAUCGACCCCGG




CAGCGGCUACAUCCCCGAGGCCCCCAGGGACGGCCAGGC




CUACGUGAGGAAGGACGGCGAGUGGGUGCUGCUGAGCA




CCUUCCUG









It should be understood that each of the ORF sequences provided herein may be combined with a 5′ and/or 3′ UTR, such as those described herein.









TABLE 26







Additional Influenza mRNA Vaccine Constructs









Name of

SEQ


antigen
Open Reading Frame (ORF) Sequences
ID NO













MRK_pH1_
DNA
ATGAAGGTGAAGCTGCTGGTGCTGCTGTGCACCTTCACCGCC
505


Con_RBD

ACCTACGCCGGCGTGGCCCCTCTGCACCTGGGCAAGTGCAAC





ATCGCCGGCTGGATCCTGGGCAACCCTGAGTGCGAGAGCCTT





AGCACAGCCTCCTCCTGGAGCTACATCGTGGAGACGAGCAGC





AGCGATAACGGGACCTGCTACCCTGGCGACTTCATCGACTAC





GAGGAGCTGAGAGAGCAGCTGAGCAGCGTGAGCAGCTTCGA





GAGATTCGAGATCTTCCCTAAGACCAGCAGCTGGCCTAACCA





CGACAGCAACAAGGGCGTGACCGCCGCCTGCCCACACGCCG





GGGCCAAGAGCTTCTACAAGAACCTGATCTGGCTGGTGAAGA





AGGGCAACAGCTACCCTAAACTGAGCAAGTCCTACATCAACG





ACAAAGGCAAGGAGGTCCTCGTGCTCTGGGGCATCCACCACC





CTAGCACCAGCGCCGATCAGCAGAGCCTGTACCAGAACGCCG





ACGCGTACGTGTTCGTGGGCACCAGCAGATACAGCAAGAAGT





TCAAGCCTGAGATCGCCATCAGACCTAAGGTGAGGGACCAGG





AGGGCAGAATGAACTACTACTGGACCCTGGTGGAGCCCGGA





GATAAGATCACATTTGAGGCCACCGGCAACCTGGTGGTGCCT





AGATACGCCTTCGCCATGGAGAGAAACGCC




mRNA
AUGAAGGUGAAGCUGCUGGUGCUGCUGUGCACCUUCACCGC
524




CACCUACGCCGGCGUGGCCCCUCUGCACCUGGGCAAGUGCA





ACAUCGCCGGCUGGAUCCUGGGCAACCCUGAGUGCGAGAGC





CUUAGCACAGCCUCCUCCUGGAGCUACAUCGUGGAGACGAG





CAGCAGCGAUAACGGGACCUGCUACCCUGGCGACUUCAUCG





ACUACGAGGAGCUGAGAGAGCAGCUGAGCAGCGUGAGCAG





CUUCGAGAGAUUCGAGAUCUUCCCUAAGACCAGCAGCUGGC





CUAACCACGACAGCAACAAGGGCGUGACCGCCGCCUGCCCA





CACGCCGGGGCCAAGAGCUUCUACAAGAACCUGAUCUGGCU





GGUGAAGAAGGGCAACAGCUACCCUAAACUGAGCAAGUCCU





ACAUCAACGACAAAGGCAAGGAGGUCCUCGUGCUCUGGGGC





AUCCACCACCCUAGCACCAGCGCCGAUCAGCAGAGCCUGUA





CCAGAACGCCGACGCGUACGUGUUCGUGGGCACCAGCAGAU





ACAGCAAGAAGUUCAAGCCUGAGAUCGCCAUCAGACCUAAG





GUGAGGGACCAGGAGGGCAGAAUGAACUACUACUGGACCC





UGGUGGAGCCCGGAGAUAAGAUCACAUUUGAGGCCACCGGC





AACCUGGUGGUGCCUAGAUACGCCUUCGCCAUGGAGAGAAA





CGCC




Protein
MKVKLLVLLCTFTATYAGVAPLHLGKCNIAGWILGNPECESLST
543




ASSWSYIVETSSSDNGTCYPGDFIDYEELREQLSSVSSFERFEIFPK





TSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPKLS





KSYINDKGKEVLVLWGIHHPSTSADQQSLYQNADAYVFVGTSR





YSKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGNLV





VPRYAFAMERNA






MRK_pH1_
DNA
ATGAAGGCCATCCTCGTGGTGCTGCTGTACACCTTTGCCACCG
506


Con_ecto

CCAACGCCGATACCCTGTGTATCGGCTACCACGCCAACAACA





GCACCGACACCGTGGATACTGTCCTGGAGAAGAACGTGACCG





TGACCCACAGCGTGAACCTGCTGGAGGACAAGCACAACGGC





AAGCTGTGCAAGCTGAGAGGCGTGGCCCCTCTGCACCTGGGC





AAGTGCAACATCGCCGGCTGGATCCTGGGCAACCCTGAGTGC





GAGAGCCTTAGCACAGCCTCCTCCTGGAGCTACATCGTGGAG





ACGAGCAGCAGCGATAACGGGACCTGCTACCCTGGCGACTTC





ATCGACTACGAGGAGCTGAGAGAGCAGCTGAGCAGCGTGAG





CAGCTTCGAGAGATTCGAGATCTTCCCTAAGACCAGCAGCTG





GCCTAACCACGACAGCAACAAGGGCGTGACCGCCGCCTGCCC





ACACGCCGGGGCCAAGAGCTTCTACAAGAACCTGATCTGGCT





GGTGAAGAAGGGCAACAGCTACCCTAAACTGAGCAAGTCCT





ACATCAACGACAAAGGCAAGGAGGTCCTCGTGCTCTGGGGCA





TCCACCACCCTAGCACCAGCGCCGATCAGCAGAGCCTGTACC





AGAACGCCGACGCGTACGTGTTCGTGGGCACCAGCAGATACA





GCAAGAAGTTCAAGCCTGAGATCGCCATCAGACCTAAGGTGA





GGGACCAGGAGGGCAGAATGAACTACTACTGGACCCTGGTG





GAGCCCGGAGATAAGATCACATTTGAGGCCACCGGCAACCTG





GTGGTGCCTAGATACGCCTTCGCCATGGAGAGAAACGCCGGC





AGCGGCATCATCATCAGCGACACCCCTGTGCACGACTGCAAC





ACCACCTGCCAGACCCCTAAGGGCGCCATCAACACGAGCCTG





CCTTTCCAGAACATCCACCCTATCACCATCGGCAAGTGCCCTA





AGTACGTGAAGTCAACCAAACTGAGACTCGCCACCGGCCTCA





GAAACGTGCCTAGCATCCAGAGCAGAGGCCTCTTCGGCGCCA





TCGCGGGATTCATCGAGGGCGGCTGGACCGGCATGGTGGACG





GCTGGTACGGCTACCACCATCAGAACGAGCAGGGCAGCGGG





TACGCGGCCGACCTCAAGAGCACCCAGAACGCCATCGACAA





GATCACCAACAAGGTGAACAGCGTGATCGAGAAGATGAACA





CCCAGTTCACCGCCGTGGGCAAGGAGTTCAACCACCTGGAGA





AGAGAATCGAGAACCTGAACAAGAAGGTGGACGACGGCTTC





CTGGACATCTGGACCTACAACGCAGAACTGCTCGTGCTTCTG





GAGAACGAGAGAACCCTGGACTACCACGACTCCAACGTGAA





GAACCTGTACGAGAAGGTGAGAAGCCAGCTGAAGAACAACG





CCAAGGAGATCGGCAACGGCTGCTTCGAGTTCTACCACAAGT





GCGACAACACCTGCATGGAGAGCGTGAAGAACGGCACCTAC





GACTACCCTAAGTACAGCGAGGAGGCCAAGCTGAACAGAGA





GGAGATCGACGGCGTGAAGCTGGAGAGCACCAGAATCGGCT





CAGCCGGGAGCGCCGGCTACATCCCTGAGGCCCCTAGAGACG





GCCAGGCCTACGTGAGAAAGGACGGCGAGTGGGTGCTGCTG





AGCACCTTCCTG




mRNA
AUGAAGGCCAUCCUCGUGGUGCUGCUGUACACCUUUGCCAC
525




CGCCAACGCCGAUACCCUGUGUAUCGGCUACCACGCCAACA





ACAGCACCGACACCGUGGAUACUGUCCUGGAGAAGAACGUG





ACCGUGACCCACAGCGUGAACCUGCUGGAGGACAAGCACAA





CGGCAAGCUGUGCAAGCUGAGAGGCGUGGCCCCUCUGCACC





UGGGCAAGUGCAACAUCGCCGGCUGGAUCCUGGGCAACCCU





GAGUGCGAGAGCCUUAGCACAGCCUCCUCCUGGAGCUACAU





CGUGGAGACGAGCAGCAGCGAUAACGGGACCUGCUACCCUG





GCGACUUCAUCGACUACGAGGAGCUGAGAGAGCAGCUGAGC





AGCGUGAGCAGCUUCGAGAGAUUCGAGAUCUUCCCUAAGAC





CAGCAGCUGGCCUAACCACGACAGCAACAAGGGCGUGACCG





CCGCCUGCCCACACGCCGGGGCCAAGAGCUUCUACAAGAAC





CUGAUCUGGCUGGUGAAGAAGGGCAACAGCUACCCUAAACU





GAGCAAGUCCUACAUCAACGACAAAGGCAAGGAGGUCCUCG





UGCUCUGGGGCAUCCACCACCCUAGCACCAGCGCCGAUCAG





CAGAGCCUGUACCAGAACGCCGACGCGUACGUGUUCGUGGG





CACCAGCAGAUACAGCAAGAAGUUCAAGCCUGAGAUCGCCA





UCAGACCUAAGGUGAGGGACCAGGAGGGCAGAAUGAACUA





CUACUGGACCCUGGUGGAGCCCGGAGAUAAGAUCACAUUUG





AGGCCACCGGCAACCUGGUGGUGCCUAGAUACGCCUUCGCC





AUGGAGAGAAACGCCGGCAGCGGCAUCAUCAUCAGCGACAC





CCCUGUGCACGACUGCAACACCACCUGCCAGACCCCUAAGG





GCGCCAUCAACACGAGCCUGCCUUUCCAGAACAUCCACCCU





AUCACCAUCGGCAAGUGCCCUAAGUACGUGAAGUCAACCAA





ACUGAGACUCGCCACCGGCCUCAGAAACGUGCCUAGCAUCC





AGAGCAGAGGCCUCUUCGGCGCCAUCGCGGGAUUCAUCGAG





GGCGGCUGGACCGGCAUGGUGGACGGCUGGUACGGCUACCA





CCAUCAGAACGAGCAGGGCAGCGGGUACGCGGCCGACCUCA





AGAGCACCCAGAACGCCAUCGACAAGAUCACCAACAAGGUG





AACAGCGUGAUCGAGAAGAUGAACACCCAGUUCACCGCCGU





GGGCAAGGAGUUCAACCACCUGGAGAAGAGAAUCGAGAAC





CUGAACAAGAAGGUGGACGACGGCUUCCUGGACAUCUGGAC





CUACAACGCAGAACUGCUCGUGCUUCUGGAGAACGAGAGAA





CCCUGGACUACCACGACUCCAACGUGAAGAACCUGUACGAG





AAGGUGAGAAGCCAGCUGAAGAACAACGCCAAGGAGAUCG





GCAACGGCUGCUUCGAGUUCUACCACAAGUGCGACAACACC





UGCAUGGAGAGCGUGAAGAACGGCACCUACGACUACCCUAA





GUACAGCGAGGAGGCCAAGCUGAACAGAGAGGAGAUCGAC





GGCGUGAAGCUGGAGAGCACCAGAAUCGGCUCAGCCGGGAG





CGCCGGCUACAUCCCUGAGGCCCCUAGAGACGGCCAGGCCU





ACGUGAGAAAGGACGGCGAGUGGGUGCUGCUGAGCACCUU





CCUG




Protein
MKAILVVLLYTFATANADTLCIGYHANNSTDTVDTVLEKNVTV
544




THSVNLLEDKHNGKLCKLRGVAPLHLGKCNIAGWILGNPECESL





STASSWSYIVETSSSDNGTCYPGDFIDYEELREQLSSVSSFERFEIF





PKTSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPK





LSKSYINDKGKEVLVLWGIHHPSTSADQQSLYQNADAYVFVGT





SRYSKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGN





LVVPRYAFAMERNAGSGIIISDTPVHDCNTTCQTPKGAINTSLPF





QNIHPITIGKCPKYVKSTKLRLATGLRNVPSIQSRGLFGAIAGFIE





GGWTGMVDGWYGYHHQNEQGSGYAADLKSTQNAIDKITNKV





NSVIEKMNTQFTAVGKEFNHLEKRIENLNKKVDDGFLDIWTYN





AELLVLLENERTLDYHDSNVKNLYEKVRSQLKNNAKEIGNGCF





EFYHKCDNTCMESVKNGTYDYPKYSEEAKLNREEIDGVKLEST





RIGSAGSAGYIPEAPRDGQAYVRKDGEWVLLSTFL






MRK_sH1_
DNA
ATGAAGGTGAAGCTGCTGGTGCTGCTGTGCACCTTCACCGCC
507


Con_RBD

ACCTACGCCGGAATCGCTCCCCTGCAGCTCGGCAACTGCAGC





GTGGCCGGCTGGATTCTGGGCAACCCCGAGTGCGAACTGCTG





ATTAGCAAAGAGTCCTGGAGCTACATCGTGGAAACCCCGAAT





CCCGAGAACGGCACCTGCTACCCCGGCTACTTCGCCGACTAC





GAGGAGCTAAGAGAGCAGCTGAGTAGCGTGAGCTCATTCGA





GAGATTCGAGATCTTTCCCAAGGAGTCTAGCTGGCCCAATCA





CACCGTCACCGGCGTGTCCGCCAGCTGTAGCCACAACGGCAA





GAGCAGCTTCTACAGAAACCTGCTGTGGCTGACCGGCAAGAA





CGGACTGTACCCTAACCTGAGCAAGAGCTACGCGAACAATAA





GGAGAAGGAGGTGCTAGTGCTGTGGGGCGTGCACCATCCGCC





CAACATCGGCGACCAGAGAGCCCTGTACCACACCGAGAACG





CCTACGTGAGCGTGGTGAGCAGCCACTATAGCAGAAGATTCA





CCCCTGAGATCGCCAAGAGGCCAAAGGTGAGAGATCAGGAA





GGAAGAATAAACTACTACTGGACCCTCCTGGAGCCCGGCGAC





ACCATCATCTTCGAGGCTAACGGCAACCTGATCGCCCCTAGA





TACGCCTTCGCCCTGAGCAGAGGC




mRNA
AUGAAGGUGAAGCUGCUGGUGCUGCUGUGCACCUUCACCGC
526




CACCUACGCCGGAAUCGCUCCCCUGCAGCUCGGCAACUGCA





GCGUGGCCGGCUGGAUUCUGGGCAACCCCGAGUGCGAACUG





CUGAUUAGCAAAGAGUCCUGGAGCUACAUCGUGGAAACCCC





GAAUCCCGAGAACGGCACCUGCUACCCCGGCUACUUCGCCG





ACUACGAGGAGCUAAGAGAGCAGCUGAGUAGCGUGAGCUC





AUUCGAGAGAUUCGAGAUCUUUCCCAAGGAGUCUAGCUGG





CCCAAUCACACCGUCACCGGCGUGUCCGCCAGCUGUAGCCA





CAACGGCAAGAGCAGCUUCUACAGAAACCUGCUGUGGCUGA





CCGGCAAGAACGGACUGUACCCUAACCUGAGCAAGAGCUAC





GCGAACAAUAAGGAGAAGGAGGUGCUAGUGCUGUGGGGCG





UGCACCAUCCGCCCAACAUCGGCGACCAGAGAGCCCUGUAC





CACACCGAGAACGCCUACGUGAGCGUGGUGAGCAGCCACUA





UAGCAGAAGAUUCACCCCUGAGAUCGCCAAGAGGCCAAAGG





UGAGAGAUCAGGAAGGAAGAAUAAACUACUACUGGACCCU





CCUGGAGCCCGGCGACACCAUCAUCUUCGAGGCUAACGGCA





ACCUGAUCGCCCCUAGAUACGCCUUCGCCCUGAGCAGAGGC




Protein
MKVKLLVLLCTFTATYAGIAPLQLGNCSVAGWILGNPECELLIS
545




KESWSYIVETPNPENGTCYPGYFADYEELREQLSSVSSFERFEIFP





KESSWPNHTVTGVSASCSHNGKSSFYRNLLWLTGKNGLYPNLS





KSYANNKEKEVLVLWGVHHPPNIGDQRALYHTENAYVSVVSSH





YSRRFTPEIAKRPKVRDQEGRINYYWTLLEPGDTIIFEANGNLIAP





RYAFALSRG






MRK_sH1_
DNA
ATGAAGGTGAAGCTGCTGGTGCTGCTGTGTACCTTCACTGCC
508


Con_ecto

ACTTACGCCGACACCATTTGCATCGGCTACCACGCCAACAAC





AGCACCGATACCGTGGACACCGTGCTGGAGAAGAACGTCACC





GTGACCCACAGCGTGAACCTGCTGGAGGATAGCCATAACGGC





AAGCTGTGCCTGCTGAAGGGAATCGCTCCCCTGCAGCTCGGC





AACTGCAGCGTGGCCGGCTGGATTCTGGGCAACCCCGAGTGC





GAACTGCTGATTAGCAAAGAGTCCTGGAGCTACATCGTGGAA





ACCCCGAATCCCGAGAACGGCACCTGCTACCCCGGCTACTTC





GCCGACTACGAGGAGCTAAGAGAGCAGCTGAGTAGCGTGAG





CTCATTCGAGAGATTCGAGATCTTTCCCAAGGAGTCTAGCTG





GCCCAATCACACCGTCACCGGCGTGTCCGCCAGCTGTAGCCA





CAACGGCAAGAGCAGCTTCTACAGAAACCTGCTGTGGCTGAC





CGGCAAGAACGGACTGTACCCTAACCTGAGCAAGAGCTACGC





GAACAATAAGGAGAAGGAGGTGCTAGTGCTGTGGGGCGTGC





ACCATCCGCCCAACATCGGCGACCAGAGAGCCCTGTACCACA





CCGAGAACGCCTACGTGAGCGTGGTGAGCAGCCACTATAGCA





GAAGATTCACCCCTGAGATCGCCAAGAGGCCAAAGGTGAGA





GATCAGGAAGGAAGAATAAACTACTACTGGACCCTCCTGGAG





CCCGGCGACACCATCATCTTCGAGGCTAACGGCAACCTGATC





GCCCCTAGATACGCCTTCGCCCTGAGCAGAGGCTTCGGCAGC





GGCATCATCACCAGCAACGCTCCCATGGACGAGTGCGACGCC





AAGTGCCAGACCCCGCAGGGCGCCATCAACTCGAGCCTGCCC





TTCCAGAACGTGCACCCCGTGACCATCGGCGAGTGCCCCAAG





TACGTGAGAAGCGCCAAGCTGAGAATGGTGACCGGCCTGAG





AAACATCCCAAGCATCCAGAGCAGAGGGCTGTTCGGCGCCAT





CGCTGGCTTCATCGAGGGCGGCTGGACCGGCATGGTGGACGG





CTGGTACGGTTATCACCACCAGAACGAGCAGGGCAGCGGCTA





CGCCGCCGACCAGAAGTCCACCCAGAACGCCATCAACGGCAT





TACAAACAAGGTGAACAGCGTTATCGAGAAGATGAACACCC





AATTCACCGCCGTGGGCAAGGAGTTCAACAAGCTGGAGAGA





AGAATGGAGAACCTGAACAAGAAGGTGGACGACGGCTTCCT





GGACATCTGGACCTACAACGCCGAACTGCTGGTCCTGCTGGA





GAACGAGAGAACCCTGGACTTCCACGACTCCAACGTGAAGA





ACTTATACGAGAAGGTCAAATCCCAGCTGAAGAACAACGCCA





AAGAAATCGGAAACGGCTGCTTCGAATTCTACCACAAGTGCA





ACGACGAGTGCATGGAGAGCGTGAAGAACGGAACCTACGAC





TACCCCAAGTACAGCGAGGAAAGCAAACTGAACAGAGAGAA





GATCGACGGCGTGAAGTTAGAGAGCATGGGCGTGGGCAGCG





CCGGCTCTGCTGGATACATCCCTGAGGCCCCTAGAGACGGCC





AGGCCTACGTGAGAAAGGACGGCGAGTGGGTGCTGCTGAGC





ACCTTCCTG




mRNA
AUGAAGGUGAAGCUGCUGGUGCUGCUGUGUACCUUCACUG
527




CCACUUACGCCGACACCAUUUGCAUCGGCUACCACGCCAAC





AACAGCACCGAUACCGUGGACACCGUGCUGGAGAAGAACGU





CACCGUGACCCACAGCGUGAACCUGCUGGAGGAUAGCCAUA





ACGGCAAGCUGUGCCUGCUGAAGGGAAUCGCUCCCCUGCAG





CUCGGCAACUGCAGCGUGGCCGGCUGGAUUCUGGGCAACCC





CGAGUGCGAACUGCUGAUUAGCAAAGAGUCCUGGAGCUAC





AUCGUGGAAACCCCGAAUCCCGAGAACGGCACCUGCUACCC





CGGCUACUUCGCCGACUACGAGGAGCUAAGAGAGCAGCUGA





GUAGCGUGAGCUCAUUCGAGAGAUUCGAGAUCUUUCCCAA





GGAGUCUAGCUGGCCCAAUCACACCGUCACCGGCGUGUCCG





CCAGCUGUAGCCACAACGGCAAGAGCAGCUUCUACAGAAAC





CUGCUGUGGCUGACCGGCAAGAACGGACUGUACCCUAACCU





GAGCAAGAGCUACGCGAACAAUAAGGAGAAGGAGGUGCUA





GUGCUGUGGGGCGUGCACCAUCCGCCCAACAUCGGCGACCA





GAGAGCCCUGUACCACACCGAGAACGCCUACGUGAGCGUGG





UGAGCAGCCACUAUAGCAGAAGAUUCACCCCUGAGAUCGCC





AAGAGGCCAAAGGUGAGAGAUCAGGAAGGAAGAAUAAACU





ACUACUGGACCCUCCUGGAGCCCGGCGACACCAUCAUCUUC





GAGGCUAACGGCAACCUGAUCGCCCCUAGAUACGCCUUCGC





CCUGAGCAGAGGCUUCGGCAGCGGCAUCAUCACCAGCAACG





CUCCCAUGGACGAGUGCGACGCCAAGUGCCAGACCCCGCAG





GGCGCCAUCAACUCGAGCCUGCCCUUCCAGAACGUGCACCC





CGUGACCAUCGGCGAGUGCCCCAAGUACGUGAGAAGCGCCA





AGCUGAGAAUGGUGACCGGCCUGAGAAACAUCCCAAGCAUC





CAGAGCAGAGGGCUGUUCGGCGCCAUCGCUGGCUUCAUCGA





GGGCGGCUGGACCGGCAUGGUGGACGGCUGGUACGGUUAU





CACCACCAGAACGAGCAGGGCAGCGGCUACGCCGCCGACCA





GAAGUCCACCCAGAACGCCAUCAACGGCAUUACAAACAAGG





UGAACAGCGUUAUCGAGAAGAUGAACACCCAAUUCACCGCC





GUGGGCAAGGAGUUCAACAAGCUGGAGAGAAGAAUGGAGA





ACCUGAACAAGAAGGUGGACGACGGCUUCCUGGACAUCUGG





ACCUACAACGCCGAACUGCUGGUCCUGCUGGAGAACGAGAG





AACCCUGGACUUCCACGACUCCAACGUGAAGAACUUAUACG





AGAAGGUCAAAUCCCAGCUGAAGAACAACGCCAAAGAAAUC





GGAAACGGCUGCUUCGAAUUCUACCACAAGUGCAACGACGA





GUGCAUGGAGAGCGUGAAGAACGGAACCUACGACUACCCCA





AGUACAGCGAGGAAAGCAAACUGAACAGAGAGAAGAUCGA





CGGCGUGAAGUUAGAGAGCAUGGGCGUGGGCAGCGCCGGC





UCUGCUGGAUACAUCCCUGAGGCCCCUAGAGACGGCCAGGC





CUACGUGAGAAAGGACGGCGAGUGGGUGCUGCUGAGCACC





UUCCUG




Protein
MKVKLLVLLCTFTATYADTICIGYHANNSTDTVDTVLEKNVTVT
546




HSVNLLEDSHNGKLCLLKGIAPLQLGNCSVAGWILGNPECELLIS





KESWSYIVETPNPENGTCYPGYFADYEELREQLSSVSSFERFEIFP





KESSWPNHTVTGVSASCSHNGKSSFYRNLLWLTGKNGLYPNLS





KSYANNKEKEVLVLWGVHHPPNIGDQRALYHTENAYVSVVSSH





YSRRFTPEIAKRPKVRDQEGRINYYWTLLEPGDTIIFEANGNLIAP





RYAFALSRGFGSGIITSNAPMDECDAKCQTPQGAINSSLPFQNVH





PVTIGECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGFIEGGW





TGMVDGWYGYHHQNEQGSGYAADQKSTQNAINGITNKVNSVI





EKMNTQFTAVGKEFNKLERRMENLNKKVDDGFLDIWTYNAEL





LVLLENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGCFEFY





HKCNDECMESVKNGTYDYPKYSEESKLNREKIDGVKLESMGVG





SAGSAGYIPEAPRDGQAYVRKDGEWVLLSTFL






MRK_sH1_
DNA
ATGAAGGTGAAACTCCTCGTCCTGCTGTGCACCTTCACCGCC
509


Con_v2

ACCTACGCCGATACCATCTGTATTGGCTACCACGCCAACAAC





TCCACCGACACCGTGGATACCGTGCTCGAGAAGAACGTGACC





GTGACCCACAGCGTGAACCTGCTGGAGAACAGCCACAACGG





CAAGCTGTGCCTGCTGAAGGGCATCGCGCCCCTGCAGTTGGG





TAACTGCTCCGTGGCCGGCTGGATCCTGGGCAACCCTGAGTG





CGAGCTGCTGATCAGCAAGGAGAGCTGGAGCTACATCGTGGA





GAAGCCTAACCCCGAGAACGGCACCTGCTACCCTGGCCACTT





CGCCGACTACGAGGAGCTGAGAGAGCAACTCAGCAGCGTGA





GCAGCTTCGAGAGATTCGAGATCTTCCCTAAGGAGAGCAGCT





GGCCCAATCACACTGTGACCGGCGTGTCCGCTTCTTGCAGCC





ATAACGGGGAAAGCTCCTTCTACAGAAATCTCCTTTGGCTGA





CGGGGAAGAACGGCCTGTACCCTAACCTGAGCAAGAGCTAC





GCCAACAACAAGGAGAAGGAGGTGCTGGTGCTGTGGGGCGT





GCACCACCCTCCTAACATCGGCGACCAGAAGGCCCTGTACCA





CACCGAGAACGCCTACGTCAGCGTGGTGTCCAGCCACTACAG





CAGAAAGTTCACCCCTGAGATCGCCAAGAGGCCTAAGGTGCG





GGACCAGGAGGGCAGAATCAACTACTACTGGACCCTGCTGGA





GCCTGGCGACACCATCATCTTCGAGGCCAACGGCAACCTGAT





CGCCCCTAGATACGCCTTCGCCCTGAGCAGAGGCTTCGGCAG





CGGCATCATCAACAGCAACGCCCCTATGGACAAGTGCGACGC





CAAGTGCCAGACTCCGCAGGGCGCTATCAACAGCTCCCTGCC





TTTCCAGAACGTGCACCCTGTGACCATCGGCGAGTGCCCTAA





GTACGTGAGAAGCGCCAAGCTGAGAATGGTGACCGGCCTGA





GAAACATCCCTAGCATCCAGAGCAGAGGCCTGTTCGGCGCCA





TCGCCGGGTTTATCGAGGGCGGCTGGACCGGCATGGTGGACG





GCTGGTACGGCTACCACCACCAGAACGAGCAGGGCTCCGGCT





ACGCCGCCGACCAGAAATCCACCCAGAACGCCATCAACGGC





ATCACCAACAAGGTGAACAGCGTCATCGAGAAGATGAACAC





CCAGTTCACCGCCGTGGGCAAGGAGTTCAACAAGCTGGAGAG





AAGAATGGAGAACCTGAACAAGAAGGTGGACGACGGCTTCA





TCGACATCTGGACCTACAACGCCGAGCTTCTGGTGCTCCTGG





AGAACGAGAGAACCCTGGACTTCCACGACAGCAACGTGAAG





AACCTGTACGAGAAGGTGAAGTCCCAGCTGAAGAACAACGC





CAAGGAGATCGGCAACGGCTGCTTCGAGTTCTACCACAAGTG





CAACGACGAGTGCATGGAGAGCGTGAAGAACGGCACCTACG





ATTACCCCAAGTACAGCGAGGAGAGCAAGCTGAACAGAGAG





AAGATCGACGGCGTGAAGCTGGAGAGCATGGGCGTGTACCA





GATCCTGGCCATCTACTCCACCGTGGCCAGTAGCCTGGTGCT





GCTGGTGAGCCTGGGCGCAATCAGCTTCTGGATGTGCAGCAA





CGGCAGCCTGCAGTGCAGAATCTGCATC




mRNA
AUGAAGGUGAAACUCCUCGUCCUGCUGUGCACCUUCACCGC
528




CACCUACGCCGAUACCAUCUGUAUUGGCUACCACGCCAACA





ACUCCACCGACACCGUGGAUACCGUGCUCGAGAAGAACGUG





ACCGUGACCCACAGCGUGAACCUGCUGGAGAACAGCCACAA





CGGCAAGCUGUGCCUGCUGAAGGGCAUCGCGCCCCUGCAGU





UGGGUAACUGCUCCGUGGCCGGCUGGAUCCUGGGCAACCCU





GAGUGCGAGCUGCUGAUCAGCAAGGAGAGCUGGAGCUACA





UCGUGGAGAAGCCUAACCCCGAGAACGGCACCUGCUACCCU





GGCCACUUCGCCGACUACGAGGAGCUGAGAGAGCAACUCAG





CAGCGUGAGCAGCUUCGAGAGAUUCGAGAUCUUCCCUAAGG





AGAGCAGCUGGCCCAAUCACACUGUGACCGGCGUGUCCGCU





UCUUGCAGCCAUAACGGGGAAAGCUCCUUCUACAGAAAUCU





CCUUUGGCUGACGGGGAAGAACGGCCUGUACCCUAACCUGA





GCAAGAGCUACGCCAACAACAAGGAGAAGGAGGUGCUGGU





GCUGUGGGGCGUGCACCACCCUCCUAACAUCGGCGACCAGA





AGGCCCUGUACCACACCGAGAACGCCUACGUCAGCGUGGUG





UCCAGCCACUACAGCAGAAAGUUCACCCCUGAGAUCGCCAA





GAGGCCUAAGGUGCGGGACCAGGAGGGCAGAAUCAACUAC





UACUGGACCCUGCUGGAGCCUGGCGACACCAUCAUCUUCGA





GGCCAACGGCAACCUGAUCGCCCCUAGAUACGCCUUCGCCC





UGAGCAGAGGCUUCGGCAGCGGCAUCAUCAACAGCAACGCC





CCUAUGGACAAGUGCGACGCCAAGUGCCAGACUCCGCAGGG





CGCUAUCAACAGCUCCCUGCCUUUCCAGAACGUGCACCCUG





UGACCAUCGGCGAGUGCCCUAAGUACGUGAGAAGCGCCAAG





CUGAGAAUGGUGACCGGCCUGAGAAACAUCCCUAGCAUCCA





GAGCAGAGGCCUGUUCGGCGCCAUCGCCGGGUUUAUCGAGG





GCGGCUGGACCGGCAUGGUGGACGGCUGGUACGGCUACCAC





CACCAGAACGAGCAGGGCUCCGGCUACGCCGCCGACCAGAA





AUCCACCCAGAACGCCAUCAACGGCAUCACCAACAAGGUGA





ACAGCGUCAUCGAGAAGAUGAACACCCAGUUCACCGCCGUG





GGCAAGGAGUUCAACAAGCUGGAGAGAAGAAUGGAGAACC





UGAACAAGAAGGUGGACGACGGCUUCAUCGACAUCUGGACC





UACAACGCCGAGCUUCUGGUGCUCCUGGAGAACGAGAGAAC





CCUGGACUUCCACGACAGCAACGUGAAGAACCUGUACGAGA





AGGUGAAGUCCCAGCUGAAGAACAACGCCAAGGAGAUCGGC





AACGGCUGCUUCGAGUUCUACCACAAGUGCAACGACGAGUG





CAUGGAGAGCGUGAAGAACGGCACCUACGAUUACCCCAAGU





ACAGCGAGGAGAGCAAGCUGAACAGAGAGAAGAUCGACGG





CGUGAAGCUGGAGAGCAUGGGCGUGUACCAGAUCCUGGCCA





UCUACUCCACCGUGGCCAGUAGCCUGGUGCUGCUGGUGAGC





CUGGGCGCAAUCAGCUUCUGGAUGUGCAGCAACGGCAGCCU





GCAGUGCAGAAUCUGCAUC




Protein
MKVKLLVLLCTFTATYADTICIGYHANNSTDTVDTVLEKNVTVT
547




HSVNLLENSHNGKLCLLKGIAPLQLGNCSVAGWILGNPECELLIS





KESWSYIVEKPNPENGTCYPGHFADYEELREQLSSVSSFERFEIFP





KESSWPNHTVTGVSASCSHNGESSFYRNLLWLTGKNGLYPNLS





KSYANNKEKEVLVLWGVHHPPNIGDQKALYHTENAYVSVVSS





HYSRKFTPEIAKRPKVRDQEGRINYYWTLLEPGDTIIFEANGNLI





APRYAFALSRGFGSGIINSNAPMDKCDAKCQTPQGAINSSLPFQN





VHPVTIGECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGFIEGG





WTGMVDGWYGYHHQNEQGSGYAADQKSTQNAINGITNKVNS





VIEKMNTQFTAVGKEFNKLERRMENLNKKVDDGFIDIWTYNAE





LLVLLENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGCFEFY





HKCNDECMESVKNGTYDYPKYSEESKLNREKIDGVKLESMGVY





QILAIYSTVASSLVLLVSLGAISFWMCSNGSLQCRICI






MRK_RBS-
DNA
ATGAAGGTCAAACTTCTCGTGCTCCTGTGCACCTTCACCGCCA
510


HA129

CCTACGCGGGCGTGGCTCCGCTTCACCTGGGCAAGTGCAACA





TCGCCGGTTGGCTGCTGGGTAACCCAGAGTGCGAGCTACTGC





TGACCGTGAGCAGCTGGAGCTACATCGTGGAAACCAGCAACA





GCGACAACGGCACCTGCTACCCTGGCGACTTCATCAACTACG





AGGAGCTGAGAGAGCAGCTCAGCAGCGTGTCCAGCTTCGAG





AGATTCGAGATCTTCCCTAAGACTAGCAGCTGGCCCGACCAC





GAAACAAACAGAGGCGTGACCGCCGCTTGTCCATACGCCGGC





GCCAACAGCTTCTACAGAAACCTGATCTGGCTGGTGAAGAAG





GGCAACAGCTACCCTAAGCTGAGCAAGAGCTACGTGAACAA





CAAGGGCAAGGAGGTGCTTGTGCTGTGGGGCATCCACCACCC





TCCTACCAGCACCGACCAGCAGAGCCTGTACCAGAACGCCGA





CGCCTACGTGTTCGTGGGCAGCAGCAGATACAGCAAGAAGTT





CAAGCCTGAGATCGCCATCAGACCTAAGGTGAGGGACCAGG





AGGGCAGAATGAACTACTACTGGACTCTGGTGGAGCCCGGCG





ACAAGATCACCTTCGAGGCCACCGGCAACCTGGTGGTGCCTA





GATACGCCTTCGCCATGGAGAGAAACGCC




mRNA
AUGAAGGUCAAACUUCUCGUGCUCCUGUGCACCUUCACCGC
529




CACCUACGCGGGCGUGGCUCCGCUUCACCUGGGCAAGUGCA





ACAUCGCCGGUUGGCUGCUGGGUAACCCAGAGUGCGAGCUA





CUGCUGACCGUGAGCAGCUGGAGCUACAUCGUGGAAACCAG





CAACAGCGACAACGGCACCUGCUACCCUGGCGACUUCAUCA





ACUACGAGGAGCUGAGAGAGCAGCUCAGCAGCGUGUCCAGC





UUCGAGAGAUUCGAGAUCUUCCCUAAGACUAGCAGCUGGCC





CGACCACGAAACAAACAGAGGCGUGACCGCCGCUUGUCCAU





ACGCCGGCGCCAACAGCUUCUACAGAAACCUGAUCUGGCUG





GUGAAGAAGGGCAACAGCUACCCUAAGCUGAGCAAGAGCU





ACGUGAACAACAAGGGCAAGGAGGUGCUUGUGCUGUGGGG





CAUCCACCACCCUCCUACCAGCACCGACCAGCAGAGCCUGU





ACCAGAACGCCGACGCCUACGUGUUCGUGGGCAGCAGCAGA





UACAGCAAGAAGUUCAAGCCUGAGAUCGCCAUCAGACCUAA





GGUGAGGGACCAGGAGGGCAGAAUGAACUACUACUGGACU





CUGGUGGAGCCCGGCGACAAGAUCACCUUCGAGGCCACCGG





CAACCUGGUGGUGCCUAGAUACGCCUUCGCCAUGGAGAGAA





ACGCC




Protein
MKVKLLVLLCTFTATYAGVAPLHLGKCNIAGWLLGNPECELLL
548




TVSSWSYIVETSNSDNGTCYPGDFINYEELREQLSSVSSFERFEIF





PKTSSWPDHETNRGVTAACPYAGANSFYRNLIWLVKKGNSYPK





LSKSYVNNKGKEVLVLWGIHHPPTSTDQQSLYQNADAYVFVGS





SRYSKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGN





LVVPRYAFAMERNA






MRK_H1_
DNA
ATGAAGGCCATCCTGGTCGTGCTGCTCTACACATTCGCCACC
511


cot_all

GCCAACGCAGACACTCTGTGCATCGGCTACCACGCCAACAAC





AGCACCGACACCGTGGATACCGTGCTGGAGAAGAACGTGAC





CGTGACCCACAGCGTGAACCTGCTGGAGGACAAGCACAACG





GCAAGCTGTGCAAGCTGAGAGGCGTGGCCCCTCTGCACCTGG





GCAAGTGCAACATCGCCGGCTGGATCCTGGGAAACCCCGAGT





GCGAGAGCCTGTCAACCGCCTCGAGCTGGTCCTACATCGTGG





AAACCAGCAGCAGCGATAACGGGACGTGCTACCCGGGCGAC





TTCATCAACTACGAGGAGCTGAGAGAACAGCTGAGCAGCGTC





AGTAGCTTCGAGAGATTCGAGATCTTCCCTAAGACCAGCAGC





TGGCCTAACCACGACAGCAACAAGGGCGTGACCGCCGCTTGC





CCGCACGCAGGCGCCAAGAGCTTCTACAAGAACCTGATCTGG





CTGGTGAAGAAGGGCAACAGCTACCCTAAGCTGAGCAAGAG





CTACATCAACGACAAGGGGAAGGAGGTGCTAGTCCTGTGGG





GCATCCATCACCCTAGCACCACAGCCGACCAGCAAAGCCTGT





ACCAGAACGCGGACGCCTACGTGTTCGTCGGCACCAGCAGAT





ACAGCAAGAAGTTCAAGCCTGAGATCGCCATCAGACCTAAGG





TGCGAGATCAGGAGGGCAGAATGAACTACTACTGGACCCTGG





TGGAGCCCGGAGACAAGATTACTTTCGAAGCGACCGGCAACC





TGGTGGTGCCTAGATACGCCTTCGCCATGGAGAGAAACGCCG





GCAGCGGCATCATCATCAGCGACACCCCTGTGCACGACTGCA





ACACCACCTGCCAGACCCCTAAAGGCGCCATCAACACAAGCC





TGCCTTTTCAGAACATCCACCCTATCACCATCGGCAAGTGCCC





TAAGTACGTGAAGTCCACCAAGCTCCGCCTGGCAACCGGCCT





CAGGAACGTGCCTAGCATCCAGAGCAGAGGCCTGTTCGGGGC





CATAGCCGGCTTCATAGAGGGTGGCTGGACCGGCATGGTTGA





CGGGTGGTACGGATACCATCACCAGAACGAGCAAGGCAGCG





GCTACGCCGCAGACCTGAAGTCAACCCAGAACGCCATCGACA





AGATCACCAACAAGGTGAACAGCGTGATCGAGAAGATGAAC





ACCCAGTTCACCGCCGTGGGCAAGGAGTTCAACCACCTAGAG





AAGAGGATCGAGAACCTGAATAAGAAGGTGGACGACGGCTT





CCTGGACATCTGGACCTACAACGCCGAGCTGCTCGTCCTCCT





GGAGAACGAGAGAACCCTGGACTACCACGATAGCAACGTGA





AGAACCTGTACGAGAAGGTGAGAAACCAGCTGAAGAATAAC





GCCAAGGAGATCGGCAACGGCTGCTTCGAGTTCTACCACAAG





TGCGACAACACCTGCATGGAGAGCGTGAAGAACGGCACCTA





CGACTACCCTAAGTACAGCGAGGAGGCCAAGCTGAACAGAG





AGAAGATCGACGGCGTGAAGCTGGAGAGCACCAGAATCTAC





CAGATCCTGGCCATCTACAGCACCGTGGCCAGCAGCCTCGTG





CTCGTGGTGAGCCTGGGCGCCATCTCCTTCTGGATGTGCAGC





AACGGCAGCCTGCAGTGCAGAATCTGCATC




mRNA
AUGAAGGCCAUCCUGGUCGUGCUGCUCUACACAUUCGCCAC
530




CGCCAACGCAGACACUCUGUGCAUCGGCUACCACGCCAACA





ACAGCACCGACACCGUGGAUACCGUGCUGGAGAAGAACGUG





ACCGUGACCCACAGCGUGAACCUGCUGGAGGACAAGCACAA





CGGCAAGCUGUGCAAGCUGAGAGGCGUGGCCCCUCUGCACC





UGGGCAAGUGCAACAUCGCCGGCUGGAUCCUGGGAAACCCC





GAGUGCGAGAGCCUGUCAACCGCCUCGAGCUGGUCCUACAU





CGUGGAAACCAGCAGCAGCGAUAACGGGACGUGCUACCCGG





GCGACUUCAUCAACUACGAGGAGCUGAGAGAACAGCUGAGC





AGCGUCAGUAGCUUCGAGAGAUUCGAGAUCUUCCCUAAGAC





CAGCAGCUGGCCUAACCACGACAGCAACAAGGGCGUGACCG





CCGCUUGCCCGCACGCAGGCGCCAAGAGCUUCUACAAGAAC





CUGAUCUGGCUGGUGAAGAAGGGCAACAGCUACCCUAAGCU





GAGCAAGAGCUACAUCAACGACAAGGGGAAGGAGGUGCUA





GUCCUGUGGGGCAUCCAUCACCCUAGCACCACAGCCGACCA





GCAAAGCCUGUACCAGAACGCGGACGCCUACGUGUUCGUCG





GCACCAGCAGAUACAGCAAGAAGUUCAAGCCUGAGAUCGCC





AUCAGACCUAAGGUGCGAGAUCAGGAGGGCAGAAUGAACU





ACUACUGGACCCUGGUGGAGCCCGGAGACAAGAUUACUUUC





GAAGCGACCGGCAACCUGGUGGUGCCUAGAUACGCCUUCGC





CAUGGAGAGAAACGCCGGCAGCGGCAUCAUCAUCAGCGACA





CCCCUGUGCACGACUGCAACACCACCUGCCAGACCCCUAAA





GGCGCCAUCAACACAAGCCUGCCUUUUCAGAACAUCCACCC





UAUCACCAUCGGCAAGUGCCCUAAGUACGUGAAGUCCACCA





AGCUCCGCCUGGCAACCGGCCUCAGGAACGUGCCUAGCAUC





CAGAGCAGAGGCCUGUUCGGGGCCAUAGCCGGCUUCAUAGA





GGGUGGCUGGACCGGCAUGGUUGACGGGUGGUACGGAUAC





CAUCACCAGAACGAGCAAGGCAGCGGCUACGCCGCAGACCU





GAAGUCAACCCAGAACGCCAUCGACAAGAUCACCAACAAGG





UGAACAGCGUGAUCGAGAAGAUGAACACCCAGUUCACCGCC





GUGGGCAAGGAGUUCAACCACCUAGAGAAGAGGAUCGAGA





ACCUGAAUAAGAAGGUGGACGACGGCUUCCUGGACAUCUG





GACCUACAACGCCGAGCUGCUCGUCCUCCUGGAGAACGAGA





GAACCCUGGACUACCACGAUAGCAACGUGAAGAACCUGUAC





GAGAAGGUGAGAAACCAGCUGAAGAAUAACGCCAAGGAGA





UCGGCAACGGCUGCUUCGAGUUCUACCACAAGUGCGACAAC





ACCUGCAUGGAGAGCGUGAAGAACGGCACCUACGACUACCC





UAAGUACAGCGAGGAGGCCAAGCUGAACAGAGAGAAGAUC





GACGGCGUGAAGCUGGAGAGCACCAGAAUCUACCAGAUCCU





GGCCAUCUACAGCACCGUGGCCAGCAGCCUCGUGCUCGUGG





UGAGCCUGGGCGCCAUCUCCUUCUGGAUGUGCAGCAACGGC





AGCCUGCAGUGCAGAAUCUGCAUC




Protein
MKAILVVLLYTFATANADTLCIGYHANNSTDTVDTVLEKNVTV
549




THSVNLLEDKHNGKLCKLRGVAPLHLGKCNIAGWILGNPECESL





STASSWSYIVETSSSDNGTCYPGDFINYEELREQLSSVSSFERFEIF





PKTSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPK





LSKSYINDKGKEVLVLWGIHHPSTTADQQSLYQNADAYVFVGT





SRYSKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGN





LVVPRYAFAMERNAGSGIIISDTPVHDCNTTCQTPKGAINTSLPF





QNIHPITIGKCPKYVKSTKLRLATGLRNVPSIQSRGLFGAIAGFIE





GGWTGMVDGWYGYHHQNEQGSGYAADLKSTQNAIDKITNKV





NSVIEKMNTQFTAVGKEFNHLEKRIENLNKKVDDGFLDIWTYN





AELLVLLENERTLDYHDSNVKNLYEKVRNQLKNNAKEIGNGCF





EFYHKCDNTCMESVKNGTYDYPKYSEEAKLNREKIDGVKLEST





RIYQILAIYSTVASSLVLVVSLGAISFWMCSNGSLQCRICI






MRK_H3_
DNA
ATGAAGACCATCATCGCCCTGAGCTACATCCTGTGCCTGGTG
512


ConA

TTCGCGCAGAAACTCCCCGGCAACGACAATAGCACTGCCACC





CTGTGTCTGGGCCATCACGCCGTGCCTAACGGAACCCTCGTG





AAGACGATCACCAACGACCAGATCGAGGTGACCAACGCCAC





CGAGCTGGTCCAGAGTTCGAGCACCGGCAGAATCTGCGACAG





CCCTCACCGGATCCTGGACGGCGAGAACTGCACCCTGATTGA





CGCACTGCTAGGCGACCCACACTGTGACGGCTTCCAGAACAA





GGAGTGGGACCTGTTCGTGGAGAGAAGCAAGGCCTACAGCA





ACTGCTACCCTTACGACGTGCCTGACTACGCCAGCCTGAGAT





CCCTCGTGGCCTCCAGCGGCACCCTCGAGTTCAATAACGAGA





GCTTCAACTGGACCGGAGTCGCCCAGAACGGGACATCCTACG





CCTGCAAGAGAGGAAGCGTCAAGAGCTTCTTCAGCAGACTGA





ACTGGCTGCACCAGCTGAAGTACAAGTACCCTGCCCTGAACG





TGACCATGCCTAACAACGACAAGTTCGACAAGCTGTACATCT





GGGGCGTGCACCATCCCAGCACCGACAGCGACCAGACCTCCC





TGTACGTCCAGGCATCCGGCAGGGTCACCGTGAGCACCAAGA





GAAGCCAGCAGACCGTGATCCCTAACATCGGCAGCAGACCTT





GGGTCAGAGGCGTCTCTAGCAGAATCAGCATCTACTGGACCA





TAGTGAAGCCCGGCGACATCCTGCTGATCAACTCGACCGGCA





ACCTGATCGCTCCTAGGGGCTACTTCAAGATCAGAAGCGGCA





AGAGCAGCATCATGAGAAGCGACGCGCCCATCGGGAAGTGC





AACTCCGAGTGCATCACCCCTAACGGCAGCATCCCCAACGAC





AAGCCTTTCCAGAACGTGAACAGAATCACCTACGGCGCCTGC





CCTAGATACGTGAAGCAGAACACACTGAAGCTGGCCACCGGC





ATGAGGAACGTGCCTGAGAAGCAGACCAGAGGCATCTTCGG





GGCTATTGCCGGCTTCATCGAGAACGGTTGGGAGGGAATGGT





CGACGGGTGGTACGGCTTCAGACACCAGAACAGCGAAGGCA





CGGGACAGGCCGCCGACCTCAAGTCCACCCAGGCTGCCATCA





ATCAGATCAACGGGAAGCTGAACAGACTGATCGAGAAGACC





AACGAGAAGTTCCACCAGATCGAGAAGGAGTTCAGCGAGGT





GGAGGGCAGAATCCAGGACCTGGAGAAGTACGTGGAGGACA





CGAAGATCGACCTGTGGAGCTACAACGCAGAGCTGTTGGTGG





CACTGGAGAACCAGCACACCATCGACCTGACCGACAGCGAG





ATGAACAAGCTGTTCGAGAGGACCAGGAAGCAGTTACGAGA





GAACGCCGAGGACATGGGAAACGGCTGTTTTAAGATCTACCA





CAAGTGCGACAACGCCTGCATCGGGAGCATCAGGAACGGGA





CCTACGACCACGACGTGTACAGAGACGAGGCCCTGAACAAC





AGATTCCAGATCAAGGGCGTGGAGCTGAAGTCCGGCTACAAG





GACTGGATCCTGTGGATCAGCTTCGCCATCAGCTGCTTCCTGC





TGTGCGTGGTCCTCCTGGGCTTTATAATGTGGGCCTGCCAGAA





GGGCAACATCAGGTGCAACATCTGCATC




mRNA
AUGAAGACCAUCAUCGCCCUGAGCUACAUCCUGUGCCUGGU
531




GUUCGCGCAGAAACUCCCCGGCAACGACAAUAGCACUGCCA





CCCUGUGUCUGGGCCAUCACGCCGUGCCUAACGGAACCCUC





GUGAAGACGAUCACCAACGACCAGAUCGAGGUGACCAACGC





CACCGAGCUGGUCCAGAGUUCGAGCACCGGCAGAAUCUGCG





ACAGCCCUCACCGGAUCCUGGACGGCGAGAACUGCACCCUG





AUUGACGCACUGCUAGGCGACCCACACUGUGACGGCUUCCA





GAACAAGGAGUGGGACCUGUUCGUGGAGAGAAGCAAGGCC





UACAGCAACUGCUACCCUUACGACGUGCCUGACUACGCCAG





CCUGAGAUCCCUCGUGGCCUCCAGCGGCACCCUCGAGUUCA





AUAACGAGAGCUUCAACUGGACCGGAGUCGCCCAGAACGGG





ACAUCCUACGCCUGCAAGAGAGGAAGCGUCAAGAGCUUCUU





CAGCAGACUGAACUGGCUGCACCAGCUGAAGUACAAGUACC





CUGCCCUGAACGUGACCAUGCCUAACAACGACAAGUUCGAC





AAGCUGUACAUCUGGGGCGUGCACCAUCCCAGCACCGACAG





CGACCAGACCUCCCUGUACGUCCAGGCAUCCGGCAGGGUCA





CCGUGAGCACCAAGAGAAGCCAGCAGACCGUGAUCCCUAAC





AUCGGCAGCAGACCUUGGGUCAGAGGCGUCUCUAGCAGAAU





CAGCAUCUACUGGACCAUAGUGAAGCCCGGCGACAUCCUGC





UGAUCAACUCGACCGGCAACCUGAUCGCUCCUAGGGGCUAC





UUCAAGAUCAGAAGCGGCAAGAGCAGCAUCAUGAGAAGCG





ACGCGCCCAUCGGGAAGUGCAACUCCGAGUGCAUCACCCCU





AACGGCAGCAUCCCCAACGACAAGCCUUUCCAGAACGUGAA





CAGAAUCACCUACGGCGCCUGCCCUAGAUACGUGAAGCAGA





ACACACUGAAGCUGGCCACCGGCAUGAGGAACGUGCCUGAG





AAGCAGACCAGAGGCAUCUUCGGGGCUAUUGCCGGCUUCAU





CGAGAACGGUUGGGAGGGAAUGGUCGACGGGUGGUACGGC





UUCAGACACCAGAACAGCGAAGGCACGGGACAGGCCGCCGA





CCUCAAGUCCACCCAGGCUGCCAUCAAUCAGAUCAACGGGA





AGCUGAACAGACUGAUCGAGAAGACCAACGAGAAGUUCCAC





CAGAUCGAGAAGGAGUUCAGCGAGGUGGAGGGCAGAAUCC





AGGACCUGGAGAAGUACGUGGAGGACACGAAGAUCGACCU





GUGGAGCUACAACGCAGAGCUGUUGGUGGCACUGGAGAAC





CAGCACACCAUCGACCUGACCGACAGCGAGAUGAACAAGCU





GUUCGAGAGGACCAGGAAGCAGUUACGAGAGAACGCCGAG





GACAUGGGAAACGGCUGUUUUAAGAUCUACCACAAGUGCG





ACAACGCCUGCAUCGGGAGCAUCAGGAACGGGACCUACGAC





CACGACGUGUACAGAGACGAGGCCCUGAACAACAGAUUCCA





GAUCAAGGGCGUGGAGCUGAAGUCCGGCUACAAGGACUGG





AUCCUGUGGAUCAGCUUCGCCAUCAGCUGCUUCCUGCUGUG





CGUGGUCCUCCUGGGCUUUAUAAUGUGGGCCUGCCAGAAGG





GCAACAUCAGGUGCAACAUCUGCAUC




Protein
MKTIIALSYILCLVFAQKLPGNDNSTATLCLGHHAVPNGTLVKTI
550




TNDQIEVTNATELVQSSSTGRICDSPHRILDGENCTLIDALLGDPH





CDGFQNKEWDLFVERSKAYSNCYPYDVPDYASLRSLVASSGTL





EFNNESFNWTGVAQNGTSYACKRGSVKSFFSRLNWLHQLKYKY





PALNVTMPNNDKFDKLYIWGVHHPSTDSDQTSLYVQASGRVTV





STKRSQQTVIPNIGSRPWVRGVSSRISIYWTIVKPGDILLINSTGNL





IAPRGYFKIRSGKSSIMRSDAPIGKCNSECITPNGSIPNDKPFQNV





NRITYGACPRYVKQNTLKLATGMRNVPEKQTRGIFGAIAGFIEN





GWEGMVDGWYGFRHQNSEGTGQAADLKSTQAAINQINGKLNR





LIEKTNEKFHQIEKEFSEVEGRIQDLEKYVEDTKIDLWSYNAELL





VALENQHTIDLTDSEMNKLFERTRKQLRENAEDMGNGCFKIYH





KCDNACIGSIRNGTYDHDVYRDEALNNRFQIKGVELKSGYKDW





ILWISFAISCFLLCVVLLGFIMWACQKGNIRCNICI






MRK_H3_
DNA
ATGAAGACCATCATCGCCCTGAGCTACATCCTGTGCCTGGTG
513


ConB

TTCGCGCAGAAACTCCCCGGCAACGACAATAGCACTGCCACC





CTGTGTCTGGGCCATCACGCCGTGCCTAACGGAACCATCGTG





AAGACGATCACCAACGACCAGATCGAGGTGACCAACGCCAC





CGAGCTGGTCCAGAATTCGAGCACCGGCGAAATCTGCGACAG





CCCTCACCAGATCCTGGACGGCGAGAACTGCACCCTGATTGA





CGCACTGCTAGGCGACCCACAGTGTGACGGCTTCCAGAACAA





GAAGTGGGACCTGTTCGTGGAGAGAAGCAAGGCCTACAGCA





ACTGCTACCCTTACGACGTGCCTGACTACGCCAGCCTGAGAT





CCCTCGTGGCCTCCAGCGGCACCCTCGAGTTCAATAACGAGA





GCTTCAACTGGACCGGAGTCACCCAGAACGGGACATCCAGCG





CCTGCATCAGAAGAAGCAACAGCAGCTTCTTCAGCAGACTGA





ACTGGCTGACCCACCTGAACTTCAAGTACCCTGCCCTGAACG





TGACCATGCCTAACAACGAGCAGTTCGACAAGCTGTACATCT





GGGGCGTGCACCATCCCGGCACCGACAAGGACCAGATCTTCC





TGTACGCCCAGAGCTCCGGCAGGATCACCGTGAGCACCAAGA





GAAGCCAGCAGGCCGTGATCCCTAACATCGGCAGCAGACCTA





GAATCAGAAACATCCCTAGCAGAATCAGCATCTACTGGACCA





TAGTGAAGCCCGGCGACATCCTGCTGATCAACTCGACCGGCA





ACCTGATCGCTCCTAGGGGCTACTTCAAGATCAGAAGCGGCA





AGAGCAGCATCATGAGAAGCGACGCGCCCATCGGGAAGTGC





AACTCCGAGTGCATCACCCCTAACGGCAGCATCCCCAACGAC





AAGCCTTTCCAGAACGTGAACAGAATCACCTACGGCGCCTGC





CCTAGATACGTGAAGCAGAGCACACTGAAGCTGGCCACCGGC





ATGAGGAACGTGCCTGAGAAGCAGACCAGAGGCATCTTCGG





GGCTATTGCCGGCTTCATCGAGAACGGTTGGGAGGGAATGGT





CGACGGGTGGTACGGCTTCAGACACCAGAACAGCGAAGGCA





GGGGACAGGCCGCCGACCTCAAGTCCACCCAGGCTGCCATCG





ATCAGATCAACGGGAAGCTGAACAGACTGATCGGCAAGACC





AACGAGAAGTTCCACCAGATCGAGAAGGAGTTCAGCGAGGT





GGAGGGCAGAATCCAGGACCTGGAGAAGTACGTGGAGGACA





CGAAGATCGACCTGTGGAGCTACAACGCAGAGCTGTTGGTGG





CACTGGAGAACCAGCACACCATCGACCTGACCGACAGCGAG





ATGAACAAGCTGTTCGAGAAGACCAAGAAGCAGTTACGAGA





GAACGCCGAGGACATGGGAAACGGCTGTTTTAAGATCTACCA





CAAGTGCGACAACGCCTGCATCGGGAGCATCAGGAACGGGA





CCTACGACCACGACGTGTACAGAGACGAGGCCCTGAACAAC





AGATTCCAGATCAAGGGCGTGGAGCTGAAGTCCGGCTACAAG





GACTGGATCCTGTGGATCAGCTTCGCCATCAGCTGCTTCCTGC





TGTGCGTGGCCCTCCTGGGCTTTATAATGTGGGCCTGCCAGA





AGGGCAACATCAGGTGCAACATCTGCATC




mRNA
AUGAAGACCAUCAUCGCCCUGAGCUACAUCCUGUGCCUGGU
532




GUUCGCGCAGAAACUCCCCGGCAACGACAAUAGCACUGCCA





CCCUGUGUCUGGGCCAUCACGCCGUGCCUAACGGAACCAUC





GUGAAGACGAUCACCAACGACCAGAUCGAGGUGACCAACGC





CACCGAGCUGGUCCAGAAUUCGAGCACCGGCGAAAUCUGCG





ACAGCCCUCACCAGAUCCUGGACGGCGAGAACUGCACCCUG





AUUGACGCACUGCUAGGCGACCCACAGUGUGACGGCUUCCA





GAACAAGAAGUGGGACCUGUUCGUGGAGAGAAGCAAGGCC





UACAGCAACUGCUACCCUUACGACGUGCCUGACUACGCCAG





CCUGAGAUCCCUCGUGGCCUCCAGCGGCACCCUCGAGUUCA





AUAACGAGAGCUUCAACUGGACCGGAGUCACCCAGAACGGG





ACAUCCAGCGCCUGCAUCAGAAGAAGCAACAGCAGCUUCUU





CAGCAGACUGAACUGGCUGACCCACCUGAACUUCAAGUACC





CUGCCCUGAACGUGACCAUGCCUAACAACGAGCAGUUCGAC





AAGCUGUACAUCUGGGGCGUGCACCAUCCCGGCACCGACAA





GGACCAGAUCUUCCUGUACGCCCAGAGCUCCGGCAGGAUCA





CCGUGAGCACCAAGAGAAGCCAGCAGGCCGUGAUCCCUAAC





AUCGGCAGCAGACCUAGAAUCAGAAACAUCCCUAGCAGAAU





CAGCAUCUACUGGACCAUAGUGAAGCCCGGCGACAUCCUGC





UGAUCAACUCGACCGGCAACCUGAUCGCUCCUAGGGGCUAC





UUCAAGAUCAGAAGCGGCAAGAGCAGCAUCAUGAGAAGCG





ACGCGCCCAUCGGGAAGUGCAACUCCGAGUGCAUCACCCCU





AACGGCAGCAUCCCCAACGACAAGCCUUUCCAGAACGUGAA





CAGAAUCACCUACGGCGCCUGCCCUAGAUACGUGAAGCAGA





GCACACUGAAGCUGGCCACCGGCAUGAGGAACGUGCCUGAG





AAGCAGACCAGAGGCAUCUUCGGGGCUAUUGCCGGCUUCAU





CGAGAACGGUUGGGAGGGAAUGGUCGACGGGUGGUACGGC





UUCAGACACCAGAACAGCGAAGGCAGGGGACAGGCCGCCGA





CCUCAAGUCCACCCAGGCUGCCAUCGAUCAGAUCAACGGGA





AGCUGAACAGACUGAUCGGCAAGACCAACGAGAAGUUCCAC





CAGAUCGAGAAGGAGUUCAGCGAGGUGGAGGGCAGAAUCC





AGGACCUGGAGAAGUACGUGGAGGACACGAAGAUCGACCU





GUGGAGCUACAACGCAGAGCUGUUGGUGGCACUGGAGAAC





CAGCACACCAUCGACCUGACCGACAGCGAGAUGAACAAGCU





GUUCGAGAAGACCAAGAAGCAGUUACGAGAGAACGCCGAG





GACAUGGGAAACGGCUGUUUUAAGAUCUACCACAAGUGCG





ACAACGCCUGCAUCGGGAGCAUCAGGAACGGGACCUACGAC





CACGACGUGUACAGAGACGAGGCCCUGAACAACAGAUUCCA





GAUCAAGGGCGUGGAGCUGAAGUCCGGCUACAAGGACUGG





AUCCUGUGGAUCAGCUUCGCCAUCAGCUGCUUCCUGCUGUG





CGUGGCCCUCCUGGGCUUUAUAAUGUGGGCCUGCCAGAAGG





GCAACAUCAGGUGCAACAUCUGCAUC




Protein
MKTIIALSYILCLVFAQKLPGNDNSTATLCLGHHAVPNGTIVKTI
551




TNDQIEVTNATELVQNSSTGEICDSPHQILDGENCTLIDALLGDP





QCDGFQNKKWDLFVERSKAYSNCYPYDVPDYASLRSLVASSGT





LEFNNESFNWTGVTQNGTSSACIRRSNSSFFSRLNWLTHLNFKYP





ALNVTMPNNEQFDKLYIWGVHHPGTDKDQIFLYAQSSGRITVST





KRSQQAVIPNIGSRPRIRNIPSRISIYWTIVKPGDILLINSTGNLIAP





RGYFKIRSGKSSIMRSDAPIGKCNSECITPNGSIPNDKPFQNVNRI





TYGACPRYVKQSTLKLATGMRNVPEKQTRGIFGAIAGFIENGWE





GMVDGWYGFRHQNSEGRGQAADLKSTQAAIDQINGKLNRLIGK





TNEKFHQIEKEFSEVEGRIQDLEKYVEDTKIDLWSYNAELLVALE





NQHTIDLTDSEMNKLFEKTKKQLRENAEDMGNGCFKIYHKCDN





ACIGSIRNGTYDHDVYRDEALNNRFQIKGVELKSGYKDWILWIS





FAISCFLLCVALLGFIMWACQKGNIRCNICI






MRK_H3_
DNA
ATGAAGACCATCATCGCCCTGAGCTACATCCTGTGCCTGGTG
514


con_all

TTCGCGCAGAAACTCCCCGGCAACGACAATAGCACTGCCACC





CTGTGTCTGGGCCATCACGCCGTGCCTAACGGAACCATCGTG





AAGACGATCACCAACGACCAGATCGAGGTGACCAACGCCAC





CGAGCTGGTCCAGAGTTCGAGCACCGGCGAAATCTGCGACAG





CCCTCACCAGATCCTGGACGGCGAGAACTGCACCCTGATTGA





CGCACTGCTAGGCGACCCACAGTGTGACGGCTTCCAGAACAA





GAAGTGGGACCTGTTCGTGGAGAGAAGCAAGGCCTACAGCA





ACTGCTACCCTTACGACGTGCCTGACTACGCCAGCCTGAGAT





CCCTCGTGGCCTCCAGCGGCACCCTCGAGTTCAATAACGAGA





GCTTCAACTGGACCGGAGTCACCCAGAACGGGACATCCAGCG





CCTGCATCAGAAGAAGCAACAGCAGCTTCTTCAGCAGACTGA





ACTGGCTGACCCACCTGAACTTCAAGTACCCTGCCCTGAACG





TGACCATGCCTAACAACGAGCAGTTCGACAAGCTGTACATCT





GGGGCGTGCACCATCCCGGCACCGACAAGGACCAGATCTTCC





TGTACGCCCAGGCATCCGGCAGGATCACCGTGAGCACCAAGA





GAAGCCAGCAGGCCGTGATCCCTAACATCGGCAGCAGACCTA





GAGTCAGAAACATCCCTAGCAGAATCAGCATCTACTGGACCA





TAGTGAAGCCCGGCGACATCCTGCTGATCAACTCGACCGGCA





ACCTGATCGCTCCTAGGGGCTACTTCAAGATCAGAAGCGGCA





AGAGCAGCATCATGAGAAGCGACGCGCCCATCGGGAAGTGC





AACTCCGAGTGCATCACCCCTAACGGCAGCATCCCCAACGAC





AAGCCTTTCCAGAACGTGAACAGAATCACCTACGGCGCCTGC





CCTAGATACGTGAAGCAGAACACACTGAAGCTGGCCACCGGC





ATGAGGAACGTGCCTGAGAAGCAGACCAGAGGCATCTTCGG





GGCTATTGCCGGCTTCATCGAGAACGGTTGGGAGGGAATGGT





CGACGGGTGGTACGGCTTCAGACACCAGAACAGCGAAGGCA





GGGGACAGGCCGCCGACCTCAAGTCCACCCAGGCTGCCATCG





ATCAGATCAACGGGAAGCTGAACAGACTGATCGGCAAGACC





AACGAGAAGTTCCACCAGATCGAGAAGGAGTTCAGCGAGGT





GGAGGGCAGAATCCAGGACCTGGAGAAGTACGTGGAGGACA





CGAAGATCGACCTGTGGAGCTACAACGCAGAGCTGTTGGTGG





CACTGGAGAACCAGCACACCATCGACCTGACCGACAGCGAG





ATGAACAAGCTGTTCGAGAAGACCAAGAAGCAGTTACGAGA





GAACGCCGAGGACATGGGAAACGGCTGTTTTAAGATCTACCA





CAAGTGCGACAACGCCTGCATCGGGAGCATCAGGAACGGGA





CCTACGACCACGACGTGTACAGAGACGAGGCCCTGAACAAC





AGATTCCAGATCAAGGGCGTGGAGCTGAAGTCCGGCTACAAG





GACTGGATCCTGTGGATCAGCTTCGCCATCAGCTGCTTCCTGC





TGTGCGTGGCCCTCCTGGGCTTTATAATGTGGGCCTGCCAGA





AGGGCAACATCAGGTGCAACATCTGCATC




mRNA
AUGAAGACCAUCAUCGCCCUGAGCUACAUCCUGUGCCUGGU
533




GUUCGCGCAGAAACUCCCCGGCAACGACAAUAGCACUGCCA





CCCUGUGUCUGGGCCAUCACGCCGUGCCUAACGGAACCAUC





GUGAAGACGAUCACCAACGACCAGAUCGAGGUGACCAACGC





CACCGAGCUGGUCCAGAGUUCGAGCACCGGCGAAAUCUGCG





ACAGCCCUCACCAGAUCCUGGACGGCGAGAACUGCACCCUG





AUUGACGCACUGCUAGGCGACCCACAGUGUGACGGCUUCCA





GAACAAGAAGUGGGACCUGUUCGUGGAGAGAAGCAAGGCC





UACAGCAACUGCUACCCUUACGACGUGCCUGACUACGCCAG





CCUGAGAUCCCUCGUGGCCUCCAGCGGCACCCUCGAGUUCA





AUAACGAGAGCUUCAACUGGACCGGAGUCACCCAGAACGGG





ACAUCCAGCGCCUGCAUCAGAAGAAGCAACAGCAGCUUCUU





CAGCAGACUGAACUGGCUGACCCACCUGAACUUCAAGUACC





CUGCCCUGAACGUGACCAUGCCUAACAACGAGCAGUUCGAC





AAGCUGUACAUCUGGGGCGUGCACCAUCCCGGCACCGACAA





GGACCAGAUCUUCCUGUACGCCCAGGCAUCCGGCAGGAUCA





CCGUGAGCACCAAGAGAAGCCAGCAGGCCGUGAUCCCUAAC





AUCGGCAGCAGACCUAGAGUCAGAAACAUCCCUAGCAGAAU





CAGCAUCUACUGGACCAUAGUGAAGCCCGGCGACAUCCUGC





UGAUCAACUCGACCGGCAACCUGAUCGCUCCUAGGGGCUAC





UUCAAGAUCAGAAGCGGCAAGAGCAGCAUCAUGAGAAGCG





ACGCGCCCAUCGGGAAGUGCAACUCCGAGUGCAUCACCCCU





AACGGCAGCAUCCCCAACGACAAGCCUUUCCAGAACGUGAA





CAGAAUCACCUACGGCGCCUGCCCUAGAUACGUGAAGCAGA





ACACACUGAAGCUGGCCACCGGCAUGAGGAACGUGCCUGAG





AAGCAGACCAGAGGCAUCUUCGGGGCUAUUGCCGGCUUCAU





CGAGAACGGUUGGGAGGGAAUGGUCGACGGGUGGUACGGC





UUCAGACACCAGAACAGCGAAGGCAGGGGACAGGCCGCCGA





CCUCAAGUCCACCCAGGCUGCCAUCGAUCAGAUCAACGGGA





AGCUGAACAGACUGAUCGGCAAGACCAACGAGAAGUUCCAC





CAGAUCGAGAAGGAGUUCAGCGAGGUGGAGGGCAGAAUCC





AGGACCUGGAGAAGUACGUGGAGGACACGAAGAUCGACCU





GUGGAGCUACAACGCAGAGCUGUUGGUGGCACUGGAGAAC





CAGCACACCAUCGACCUGACCGACAGCGAGAUGAACAAGCU





GUUCGAGAAGACCAAGAAGCAGUUACGAGAGAACGCCGAG





GACAUGGGAAACGGCUGUUUUAAGAUCUACCACAAGUGCG





ACAACGCCUGCAUCGGGAGCAUCAGGAACGGGACCUACGAC





CACGACGUGUACAGAGACGAGGCCCUGAACAACAGAUUCCA





GAUCAAGGGCGUGGAGCUGAAGUCCGGCUACAAGGACUGG





AUCCUGUGGAUCAGCUUCGCCAUCAGCUGCUUCCUGCUGUG





CGUGGCCCUCCUGGGCUUUAUAAUGUGGGCCUGCCAGAAGG





GCAACAUCAGGUGCAACAUCUGCAUC




Protein
MKTIIALSYILCLVFAQKLPGNDNSTATLCLGHHAVPNGTIVKTI
552




TNDQIEVTNATELVQSSSTGEICDSPHQILDGENCTLIDALLGDPQ





CDGFQNKKWDLFVERSKAYSNCYPYDVPDYASLRSLVASSGTL





EFNNESFNWTGVTQNGTSSACIRRSNSSFFSRLNWLTHLNFKYP





ALNVTMPNNEQFDKLYIWGVHHPGTDKDQIFLYAQASGRITVST





KRSQQAVIPNIGSRPRVRNIPSRISIYWTIVKPGDILLINSTGNLIAP





RGYFKIRSGKSSIMRSDAPIGKCNSECITPNGSIPNDKPFQNVNRI





TYGACPRYVKQNTLKLATGMRNVPEKQTRGIFGAIAGFIENGW





EGMVDGWYGFRHQNSEGRGQAADLKSTQAAIDQINGKLNRLIG





KTNEKFHQIEKEFSEVEGRIQDLEKYVEDTKIDLWSYNAELLVA





LENQHTIDLTDSEMNKLFEKTKKQLRENAEDMGNGCFKIYHKC





DNACIGSIRNGTYDHDVYRDEALNNRFQIKGVELKSGYKDWIL





WISFAISCFLLCVALLGFIMWACQKGNIRCNICI






MRK_H3_
DNA
ATGAAGACCATCATCGCCCTGAGCTACATCCTGTGCCTGGTG
515


cot_all

TTCGCGCAGAAACTCCCCGGCAACGACAATAGCACTGCCACC





CTGTGTCTGGGCCATCACGCCGTGCCTAACGGAACCATCGTG





AAGACGATCACCAACGACAGAATCGAGGTGACCAACGCCAC





CGAGCTGGTCCAGAATTCGAGCATCGGCGAAATCTGCGACAG





CCCTCACCAGATCCTGGACGGCGAGAACTGCACCCTGATTGA





CGCACTGCTAGGCGACCCACAGTGTGACGGCTTCCAGAACAA





GAAGTGGGACCTGTTCGTGGAGAGAAGCAAGGCCTACAGCA





ACTGCTACCCTTACGACGTGCCTGACTACGCCAGCCTGAGAT





CCCTCGTGGCCTCCAGCGGCACCCTCGAGTTCAATAACGAGA





GCTTCAACTGGACCGGAGTCACCCAGAACGGGACATCCAGCG





CCTGCATCAGAAGAAGCAACAGCAGCTTCTTCAGCAGACTGA





ACTGGCTGACCCACCTGAACTTCAAGTACCCTGCCCTGAACG





TGACCATGCCTAACAACGAGCAGTTCGACAAGCTGTACATCT





GGGGCGTGCACCATCCCGGCACCGACAAGGACCAGATCTTCC





TGTACGCCCAGAGCTCCGGCAGGATCACCGTGAGCACCAAGA





GAAGCCAGCAGGCCGTGATCCCTAACATCGGCAGCAGACCTA





GAATCAGAAACATCCCTAGCAGAATCAGCATCTACTGGACCA





TAGTGAAGCCCGGCGACATCCTGCTGATCAACTCGACCGGCA





ACCTGATCGCTCCTAGGGGCTACTTCAAGATCAGAAGCGGCA





AGAGCAGCATCATGAGAAGCGACGCGCCCATCGGGAAGTGC





AAGTCCGAGTGCATCACCCCTAACGGCAGCATCCCCAACGAC





AAGCCTTTCCAGAACGTGAACAGAATCACCTACGGCGCCTGC





CCTAGATACGTGAAGCAGAGCACACTGAAGCTGGCCACCGGC





ATGAGGAACGTGCCTGAGAAGCAGACCAGAGGCATCTTCGG





GGCTATTGCCGGCTTCATCGAGAACGGTTGGGAGGGAATGGT





CGACGGGTGGTACGGCTTCAGACACCAGAACAGCGAAGGCA





GGGGACAGGCCGCCGACCTCAAGTCCACCCAGGCTGCCATCG





ATCAGATCAACGGGAAGCTGAACAGACTGATCGGCAAGACC





AACGAGAAGTTCCACCAGATCGAGAAGGAGTTCAGCGAGGT





GGAGGGCAGAATCCAGGACCTGGAGAAGTACGTGGAGGACA





CGAAGATCGACCTGTGGAGCTACAACGCAGAGCTGTTGGTGG





CACTGGAGAACCAGCACACCATCGACCTGACCGACAGCGAG





ATGAACAAGCTGTTCGAGAAGACCAAGAAGCAGTTACGAGA





GAACGCCGAGGACATGGGAAACGGCTGTTTTAAGATCTACCA





CAAGTGCGACAACGCCTGCATCGGGAGCATCAGGAACGGGA





CCTACGACCACGACGTGTACAGAGACGAGGCCCTGAACAAC





AGATTCCAGATCAAGGGCGTGGAGCTGAAGTCCGGCTACAAG





GACTGGATCCTGTGGATCAGCTTCGCCATCAGCTGCTTCCTGC





TGTGCGTGGCCCTCCTGGGCTTTATAATGTGGGCCTGCCAGA





AGGGCAACATCAGGTGCAACATCTGCATC




mRNA
AUGAAGACCAUCAUCGCCCUGAGCUACAUCCUGUGCCUGGU
534




GUUCGCGCAGAAACUCCCCGGCAACGACAAUAGCACUGCCA





CCCUGUGUCUGGGCCAUCACGCCGUGCCUAACGGAACCAUC





GUGAAGACGAUCACCAACGACAGAAUCGAGGUGACCAACGC





CACCGAGCUGGUCCAGAAUUCGAGCAUCGGCGAAAUCUGCG





ACAGCCCUCACCAGAUCCUGGACGGCGAGAACUGCACCCUG





AUUGACGCACUGCUAGGCGACCCACAGUGUGACGGCUUCCA





GAACAAGAAGUGGGACCUGUUCGUGGAGAGAAGCAAGGCC





UACAGCAACUGCUACCCUUACGACGUGCCUGACUACGCCAG





CCUGAGAUCCCUCGUGGCCUCCAGCGGCACCCUCGAGUUCA





AUAACGAGAGCUUCAACUGGACCGGAGUCACCCAGAACGGG





ACAUCCAGCGCCUGCAUCAGAAGAAGCAACAGCAGCUUCUU





CAGCAGACUGAACUGGCUGACCCACCUGAACUUCAAGUACC





CUGCCCUGAACGUGACCAUGCCUAACAACGAGCAGUUCGAC





AAGCUGUACAUCUGGGGCGUGCACCAUCCCGGCACCGACAA





GGACCAGAUCUUCCUGUACGCCCAGAGCUCCGGCAGGAUCA





CCGUGAGCACCAAGAGAAGCCAGCAGGCCGUGAUCCCUAAC





AUCGGCAGCAGACCUAGAAUCAGAAACAUCCCUAGCAGAAU





CAGCAUCUACUGGACCAUAGUGAAGCCCGGCGACAUCCUGC





UGAUCAACUCGACCGGCAACCUGAUCGCUCCUAGGGGCUAC





UUCAAGAUCAGAAGCGGCAAGAGCAGCAUCAUGAGAAGCG





ACGCGCCCAUCGGGAAGUGCAAGUCCGAGUGCAUCACCCCU





AACGGCAGCAUCCCCAACGACAAGCCUUUCCAGAACGUGAA





CAGAAUCACCUACGGCGCCUGCCCUAGAUACGUGAAGCAGA





GCACACUGAAGCUGGCCACCGGCAUGAGGAACGUGCCUGAG





AAGCAGACCAGAGGCAUCUUCGGGGCUAUUGCCGGCUUCAU





CGAGAACGGUUGGGAGGGAAUGGUCGACGGGUGGUACGGC





UUCAGACACCAGAACAGCGAAGGCAGGGGACAGGCCGCCGA





CCUCAAGUCCACCCAGGCUGCCAUCGAUCAGAUCAACGGGA





AGCUGAACAGACUGAUCGGCAAGACCAACGAGAAGUUCCAC





CAGAUCGAGAAGGAGUUCAGCGAGGUGGAGGGCAGAAUCC





AGGACCUGGAGAAGUACGUGGAGGACACGAAGAUCGACCU





GUGGAGCUACAACGCAGAGCUGUUGGUGGCACUGGAGAAC





CAGCACACCAUCGACCUGACCGACAGCGAGAUGAACAAGCU





GUUCGAGAAGACCAAGAAGCAGUUACGAGAGAACGCCGAG





GACAUGGGAAACGGCUGUUUUAAGAUCUACCACAAGUGCG





ACAACGCCUGCAUCGGGAGCAUCAGGAACGGGACCUACGAC





CACGACGUGUACAGAGACGAGGCCCUGAACAACAGAUUCCA





GAUCAAGGGCGUGGAGCUGAAGUCCGGCUACAAGGACUGG





AUCCUGUGGAUCAGCUUCGCCAUCAGCUGCUUCCUGCUGUG





CGUGGCCCUCCUGGGCUUUAUAAUGUGGGCCUGCCAGAAGG





GCAACAUCAGGUGCAACAUCUGCAUC




Protein
MKTIIALSYILCLVFAQKLPGNDNSTATLCLGHHAVPNGTIVKTI
553




TNDRIEVTNATELVQNSSIGEICDSPHQILDGENCTLIDALLGDPQ





CDGFQNKKWDLFVERSKAYSNCYPYDVPDYASLRSLVASSGTL





EFNNESFNWTGVTQNGTSSACIRRSNSSFFSRLNWLTHLNFKYP





ALNVTMPNNEQFDKLYIWGVHHPGTDKDQIFLYAQSSGRITVST





KRSQQAVIPNIGSRPRIRNIPSRISIYWTIVKPGDILLINSTGNLIAP





RGYFKIRSGKSSIMRSDAPIGKCKSECITPNGSIPNDKPFQNVNRI





TYGACPRYVKQSTLKLATGMRNVPEKQTRGIFGAIAGFIENGWE





GMVDGWYGFRHQNSEGRGQAADLKSTQAAIDQINGKLNRLIGK





TNEKFHQIEKEFSEVEGRIQDLEKYVEDTKIDLWSYNAELLVALE





NQHTIDLTDSEMNKLFEKTKKQLRENAEDMGNGCFKIYHKCDN





ACIGSIRNGTYDHDVYRDEALNNRFQIKGVELKSGYKDWILWIS





FAISCFLLCVALLGFIMWACQKGNIRCNICI






RBD1-
DNA
ATGAAGGTGAAGCTTCTCGTGCTCTTATGCACCTTCACCGCCA
516


Cal09-PC-

CCTACGCCGGCGTGGCTCCGCTTCACCTTGGCAAGTGCAACA



Cb

TCGCCGGCTGGATCTTGGGAAACCCCGAGTGCGAGAGCTTGA





GCACCGCCAGCAGCTGGAGCAACATCACGGAAACCCCTAGC





AGCGACAACGGCACCTGCTACCCCGGCGACTTCATCGACTAC





GAGGAGCTGCGGGAGCAGCTGAGCAGCGTGAGCAGCTTCGA





GCGGTTCGAGATCTTCCCCAAGACCAGCTCTTGGCCCAACCA





CAGCAGCAACAAGGGCGTGACCGCCGCCTGCCCTCACGCTGG





CGCCAAGAGCTTCTACAAGAACCTGATCTGGCTGGTGAAGAA





GAACGGCAGCTACCCCAAGCTGAACAAGTCTTACATTAACGA





CTCAGGCAAGGAGGTGCTGGTCCTGTGGGGCATCCACCACCC





CAGCAACAGCACCGACCAACAGAGCCTGTACCAGAACGCCG





ACACCTACGTGTTCGTGGGCAGCAGCAACTACAGCAAGAAGT





TCAAGCCCGAGATCGCCATCCGGCCCAAGGTGCGGGACCAGG





AGGGCCGGATGAACTACTACTGGACCCTGGTGGAGCCTGGCG





ACAAGATCACCTTCGAGGCCACCGGCAACCTGGTGGTGCCCC





GGTACGCCTTCGCCATGGAGCGGAACGCC




mRNA
AUGAAGGUGAAGCUUCUCGUGCUCUUAUGCACCUUCACCGC
535




CACCUACGCCGGCGUGGCUCCGCUUCACCUUGGCAAGUGCA





ACAUCGCCGGCUGGAUCUUGGGAAACCCCGAGUGCGAGAGC





UUGAGCACCGCCAGCAGCUGGAGCAACAUCACGGAAACCCC





UAGCAGCGACAACGGCACCUGCUACCCCGGCGACUUCAUCG





ACUACGAGGAGCUGCGGGAGCAGCUGAGCAGCGUGAGCAGC





UUCGAGCGGUUCGAGAUCUUCCCCAAGACCAGCUCUUGGCC





CAACCACAGCAGCAACAAGGGCGUGACCGCCGCCUGCCCUC





ACGCUGGCGCCAAGAGCUUCUACAAGAACCUGAUCUGGCUG





GUGAAGAAGAACGGCAGCUACCCCAAGCUGAACAAGUCUUA





CAUUAACGACUCAGGCAAGGAGGUGCUGGUCCUGUGGGGC





AUCCACCACCCCAGCAACAGCACCGACCAACAGAGCCUGUA





CCAGAACGCCGACACCUACGUGUUCGUGGGCAGCAGCAACU





ACAGCAAGAAGUUCAAGCCCGAGAUCGCCAUCCGGCCCAAG





GUGCGGGACCAGGAGGGCCGGAUGAACUACUACUGGACCCU





GGUGGAGCCUGGCGACAAGAUCACCUUCGAGGCCACCGGCA





ACCUGGUGGUGCCCCGGUACGCCUUCGCCAUGGAGCGGAAC





GCC




Protein
MKVKLLVLLCTFTATYAGVAPLHLGKCNIAGWILGNPECESLST
554




ASSWSNITETPSSDNGTCYPGDFIDYEELREQLSSVSSFERFEIFPK





TSSWPNHSSNKGVTAACPHAGAKSFYKNLIWLVKKNGSYPKLN





KSYINDSGKEVLVLWGIHHPSNSTDQQSLYQNADTYVFVGSSNY





SKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGNLVV





PRYAFAMERNA






RBD1-
DNA
ATGAAGGTGAAGCTTCTCGTGCTCTTATGCACCTTCACCGCCA
517


Cal09-PC

CCTACGCCGGCGTGGCTCCGCTTCACCTTGGCAAGTGCAACA





TCGCCGGCTGGATCTTGGGAAACCCCGAGTGCGAGAGCAACA





GCACCGCCAGCAGCTGGAGCAACATCACGGAAACCCCTAGC





AGCGACAACGGCACCTGCTACCCCGGCGACTTCATCGACTAC





GAGGAGCTGCGGGAGCAGCTGAGCAGCGTGAGCAGCTTCGA





GCGGTTCGAGATCTTCCCCAAGACCAGCTCTTGGCCCAACCA





CAGCAGCAACAAGGGCGTGACCGCCGCCTGCCCTCACGCTGG





CGCCAAGAGCTTCTACAAGAACCTGATCTGGCTGGTGAAGAA





GAACGGCAGCTACCCCAAGCTGAACAAGTCTTACATTAACGA





CTCAGGCAAGGAGGTGCTGGTCCTGTGGGGCATCCACCACCC





CAGCAACAGCACCGACCAACAGAGCCTGTACCAGAACGCCG





ACACCTACGTGTTCGTGGGCAGCAGCAACTACAGCAAGAAGT





TCAAGCCCGAGATCGCCATCCGGCCCAAGGTGCGGGACCAGG





AGGGCCGGATGAACTACTACTGGACCCTGGTGGAGCCTGGCG





ACAAGATCACCTTCGAGGCCACCGGCAACCTGGTGGTGCCCC





GGTACGCCTTCGCCATGGAGCGGAACGCC




mRNA
AUGAAGGUGAAGCUUCUCGUGCUCUUAUGCACCUUCACCGC
536




CACCUACGCCGGCGUGGCUCCGCUUCACCUUGGCAAGUGCA





ACAUCGCCGGCUGGAUCUUGGGAAACCCCGAGUGCGAGAGC





AACAGCACCGCCAGCAGCUGGAGCAACAUCACGGAAACCCC





UAGCAGCGACAACGGCACCUGCUACCCCGGCGACUUCAUCG





ACUACGAGGAGCUGCGGGAGCAGCUGAGCAGCGUGAGCAGC





UUCGAGCGGUUCGAGAUCUUCCCCAAGACCAGCUCUUGGCC





CAACCACAGCAGCAACAAGGGCGUGACCGCCGCCUGCCCUC





ACGCUGGCGCCAAGAGCUUCUACAAGAACCUGAUCUGGCUG





GUGAAGAAGAACGGCAGCUACCCCAAGCUGAACAAGUCUUA





CAUUAACGACUCAGGCAAGGAGGUGCUGGUCCUGUGGGGC





AUCCACCACCCCAGCAACAGCACCGACCAACAGAGCCUGUA





CCAGAACGCCGACACCUACGUGUUCGUGGGCAGCAGCAACU





ACAGCAAGAAGUUCAAGCCCGAGAUCGCCAUCCGGCCCAAG





GUGCGGGACCAGGAGGGCCGGAUGAACUACUACUGGACCCU





GGUGGAGCCUGGCGACAAGAUCACCUUCGAGGCCACCGGCA





ACCUGGUGGUGCCCCGGUACGCCUUCGCCAUGGAGCGGAAC





GCC




Protein
MKVKLLVLLCTFTATYAGVAPLHLGKCNIAGWILGNPECESNST
555




ASSWSNITETPSSDNGTCYPGDFIDYEELREQLSSVSSFERFEIFPK





TSSWPNHSSNKGVTAACPHAGAKSFYKNLIWLVKKNGSYPKLN





KSYINDSGKEVLVLWGIHHPSNSTDQQSLYQNADTYVFVGSSNY





SKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGNLVV





PRYAFAMERNA






RBD1-
DNA
ATGAAGGTGAAGCTTCTCGTGCTCTTATGCACCTTCACCGCCA
518


Cal09

CCTACGCCGGCGTGGCTCCGCTTCACCTTGGCAAGTGCAACA





TCGCCGGCTGGATCTTGGGAAACCCCGAGTGCGAGAGCTTGA





GCACCGCCAGCAGCTGGAGCAACATCACGGAAACCCCTAGC





AGCGACAACGGCACCTGCTACCCCGGCGACTTCATCGACTAC





GAGGAGCTGCGGGAGCAGCTGAGCAGCGTGAGCAGCTTCGA





GCGGTTCGAGATCTTCCCCAAGACCAGCTCTTGGCCCAACCA





CGACAGCAACAAGGGCGTGACCGCCGCCTGCCCTCACGCTGG





CGCCAAGAGCTTCTACAAGAACCTGATCTGGCTGGTGAAGAA





GGGCAACAGCTACCCCAAGCTGTCCAAGTCTTACATTAACGA





CAAGGGCAAGGAGGTGCTGGTCCTGTGGGGCATCCACCACCC





CAGCACCAGCGCCGACCAACAGAGCCTGTACCAGAACGCCG





ACACCTACGTGTTCGTGGGCAGCAGCCGGTACAGCAAGAAGT





TCAAGCCCGAGATCGCCATCCGGCCCAAGGTGCGGGACCAGG





AGGGCCGGATGAACTACTACTGGACCCTGGTGGAGCCTGGCG





ACAAGATCACCTTCGAGGCCACCGGCAACCTGGTGGTGCCCC





GGTACGCCTTCGCCATGGAGCGGAACGCC




mRNA
AUGAAGGUGAAGCUUCUCGUGCUCUUAUGCACCUUCACCGC
537




CACCUACGCCGGCGUGGCUCCGCUUCACCUUGGCAAGUGCA





ACAUCGCCGGCUGGAUCUUGGGAAACCCCGAGUGCGAGAGC





UUGAGCACCGCCAGCAGCUGGAGCAACAUCACGGAAACCCC





UAGCAGCGACAACGGCACCUGCUACCCCGGCGACUUCAUCG





ACUACGAGGAGCUGCGGGAGCAGCUGAGCAGCGUGAGCAGC





UUCGAGCGGUUCGAGAUCUUCCCCAAGACCAGCUCUUGGCC





CAACCACGACAGCAACAAGGGCGUGACCGCCGCCUGCCCUC





ACGCUGGCGCCAAGAGCUUCUACAAGAACCUGAUCUGGCUG





GUGAAGAAGGGCAACAGCUACCCCAAGCUGUCCAAGUCUUA





CAUUAACGACAAGGGCAAGGAGGUGCUGGUCCUGUGGGGC





AUCCACCACCCCAGCACCAGCGCCGACCAACAGAGCCUGUA





CCAGAACGCCGACACCUACGUGUUCGUGGGCAGCAGCCGGU





ACAGCAAGAAGUUCAAGCCCGAGAUCGCCAUCCGGCCCAAG





GUGCGGGACCAGGAGGGCCGGAUGAACUACUACUGGACCCU





GGUGGAGCCUGGCGACAAGAUCACCUUCGAGGCCACCGGCA





ACCUGGUGGUGCCCCGGUACGCCUUCGCCAUGGAGCGGAAC





GCC




Protein
MKVKLLVLLCTFTATYAGVAPLHLGKCNIAGWILGNPECESLST
556




ASSWSNITETPSSDNGTCYPGDFIDYEELREQLSSVSSFERFEIFPK





TSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPKLS





KSYINDKGKEVLVLWGIHHPSTSADQQSLYQNADTYVFVGSSR





YSKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGNLV





VPRYAFAMERNA






MRK_RBD-
DNA
ATGAAGGTGAAGCTTCTCGTGCTCTTATGCACCTTCACCGCCA
519


Cal09-PC-

CCTACGCCGGCGTGGCTCCGCTTCACCTTGGCAAGTGCAACA



Cb

TCGCCGGCTGGATCTTGGGAAACCCCGAGTGCGAGAGCTTGA





GCACCGCCAGCAGCTGGAGCTACATCGTGGAAACCCCTAGCA





GCGACAACGGCACCTGCTACCCCGGCGACTTCATCGACTACG





AGGAGCTGCGGGAGCAGCTGAGCAGCGTGAGCAGCTTCGAG





CGGTTCGAGATCTTCCCCAAGACCAGCTCTTGGCCCAACCAC





AGCAGCAACAAGGGCGTGACCGCCGCCTGCCCTCACGCTGGC





GCCAAGAGCTTCTACAAGAACCTGATCTGGCTGGTGAAGAAG





AACGGCAGCTACCCCAAGCTGAACAAGTCTTACATTAACGAC





TCAGGCAAGGAGGTGCTGGTCCTGTGGGGCATCCACCACCCC





AGCAACAGCACCGACCAACAGAGCCTGTACCAGAACGCCGA





CACCTACGTGTTCGTGGGCAGCAGCAACTACAGCAAGAAGTT





CAAGCCCGAGATCGCCATCCGGCCCAAGGTGCGGGACCAGG





AGGGCCGGATGAACTACTACTGGACCCTGGTGGAGCCTGGCG





ACAAGATCACCTTCGAGGCCACCGGCAACCTGGTGGTGCCCC





GGTACGCCTTCGCCATGGAGCGGAACGCC




mRNA
AUGAAGGUGAAGCUUCUCGUGCUCUUAUGCACCUUCACCGC
538




CACCUACGCCGGCGUGGCUCCGCUUCACCUUGGCAAGUGCA





ACAUCGCCGGCUGGAUCUUGGGAAACCCCGAGUGCGAGAGC





UUGAGCACCGCCAGCAGCUGGAGCUACAUCGUGGAAACCCC





UAGCAGCGACAACGGCACCUGCUACCCCGGCGACUUCAUCG





ACUACGAGGAGCUGCGGGAGCAGCUGAGCAGCGUGAGCAGC





UUCGAGCGGUUCGAGAUCUUCCCCAAGACCAGCUCUUGGCC





CAACCACAGCAGCAACAAGGGCGUGACCGCCGCCUGCCCUC





ACGCUGGCGCCAAGAGCUUCUACAAGAACCUGAUCUGGCUG





GUGAAGAAGAACGGCAGCUACCCCAAGCUGAACAAGUCUUA





CAUUAACGACUCAGGCAAGGAGGUGCUGGUCCUGUGGGGC





AUCCACCACCCCAGCAACAGCACCGACCAACAGAGCCUGUA





CCAGAACGCCGACACCUACGUGUUCGUGGGCAGCAGCAACU





ACAGCAAGAAGUUCAAGCCCGAGAUCGCCAUCCGGCCCAAG





GUGCGGGACCAGGAGGGCCGGAUGAACUACUACUGGACCCU





GGUGGAGCCUGGCGACAAGAUCACCUUCGAGGCCACCGGCA





ACCUGGUGGUGCCCCGGUACGCCUUCGCCAUGGAGCGGAAC





GCC




Protein
MKVKLLVLLCTFTATYAGVAPLHLGKCNIAGWILGNPECESLST
557




ASSWSYIVETPSSDNGTCYPGDFIDYEELREQLSSVSSFERFEIFPK





TSSWPNHSSNKGVTAACPHAGAKSFYKNLIWLVKKNGSYPKLN





KSYINDSGKEVLVLWGIHHPSNSTDQQSLYQNADTYVFVGSSNY





SKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGNLVV





PRYAFAMERNA






MRK_RBD-
DNA
ATGAAGGTGAAGCTTCTCGTGCTCTTATGCACCTTCACCGCCA
520


Cal09-PC

CCTACGCCGGCGTGGCTCCGCTTCACCTTGGCAAGTGCAACA





TCGCCGGCTGGATCTTGGGAAACCCCGAGTGCGAGAGCAACA





GCACCGCCAGCAGCTGGAGCTACATCGTGGAAACCCCTAGCA





GCGACAACGGCACCTGCTACCCCGGCGACTTCATCGACTACG





AGGAGCTGCGGGAGCAGCTGAGCAGCGTGAGCAGCTTCGAG





CGGTTCGAGATCTTCCCCAAGACCAGCTCTTGGCCCAACCAC





AGCAGCAACAAGGGCGTGACCGCCGCCTGCCCTCACGCTGGC





GCCAAGAGCTTCTACAAGAACCTGATCTGGCTGGTGAAGAAG





AACGGCAGCTACCCCAAGCTGAACAAGTCTTACATTAACGAC





TCAGGCAAGGAGGTGCTGGTCCTGTGGGGCATCCACCACCCC





AGCAACAGCACCGACCAACAGAGCCTGTACCAGAACGCCGA





CACCTACGTGTTCGTGGGCAGCAGCAACTACAGCAAGAAGTT





CAAGCCCGAGATCGCCATCCGGCCCAAGGTGCGGGACCAGG





AGGGCCGGATGAACTACTACTGGACCCTGGTGGAGCCTGGCG





ACAAGATCACCTTCGAGGCCACCGGCAACCTGGTGGTGCCCC





GGTACGCCTTCGCCATGGAGCGGAACGCC




mRNA
AUGAAGGUGAAGCUUCUCGUGCUCUUAUGCACCUUCACCGC
539




CACCUACGCCGGCGUGGCUCCGCUUCACCUUGGCAAGUGCA





ACAUCGCCGGCUGGAUCUUGGGAAACCCCGAGUGCGAGAGC





AACAGCACCGCCAGCAGCUGGAGCUACAUCGUGGAAACCCC





UAGCAGCGACAACGGCACCUGCUACCCCGGCGACUUCAUCG





ACUACGAGGAGCUGCGGGAGCAGCUGAGCAGCGUGAGCAGC





UUCGAGCGGUUCGAGAUCUUCCCCAAGACCAGCUCUUGGCC





CAACCACAGCAGCAACAAGGGCGUGACCGCCGCCUGCCCUC





ACGCUGGCGCCAAGAGCUUCUACAAGAACCUGAUCUGGCUG





GUGAAGAAGAACGGCAGCUACCCCAAGCUGAACAAGUCUUA





CAUUAACGACUCAGGCAAGGAGGUGCUGGUCCUGUGGGGC





AUCCACCACCCCAGCAACAGCACCGACCAACAGAGCCUGUA





CCAGAACGCCGACACCUACGUGUUCGUGGGCAGCAGCAACU





ACAGCAAGAAGUUCAAGCCCGAGAUCGCCAUCCGGCCCAAG





GUGCGGGACCAGGAGGGCCGGAUGAACUACUACUGGACCCU





GGUGGAGCCUGGCGACAAGAUCACCUUCGAGGCCACCGGCA





ACCUGGUGGUGCCCCGGUACGCCUUCGCCAUGGAGCGGAAC





GCC




Protein
MKVKLLVLLCTFTATYAGVAPLHLGKCNIAGWILGNPECESNST
558




ASSWSYIVETPSSDNGTCYPGDFIDYEELREQLSSVSSFERFEIFPK





TSSWPNHSSNKGVTAACPHAGAKSFYKNLIWLVKKNGSYPKLN





KSYINDSGKEVLVLWGIHHPSNSTDQQSLYQNADTYVFVGSSNY





SKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGNLVV





PRYAFAMERNA






MRK_RBD-
DNA
ATGAAGGTGAAGCTTCTCGTGCTCTTATGCACCTTCACCGCCA
521


Cal09

CCTACGCCGGCGTGGCTCCGCTTCACCTTGGCAAGTGCAACA





TCGCCGGCTGGATCTTGGGAAACCCCGAGTGCGAGAGCTTGA





GCACCGCCAGCAGCTGGAGCTACATCGTGGAAACCCCTAGCA





GCGACAACGGCACCTGCTACCCCGGCGACTTCATCGACTACG





AGGAGCTGCGGGAGCAGCTGAGCAGCGTGAGCAGCTTCGAG





CGGTTCGAGATCTTCCCCAAGACCAGCTCTTGGCCCAACCAC





GACAGCAACAAGGGCGTGACCGCCGCCTGCCCTCACGCTGGC





GCCAAGAGCTTCTACAAGAACCTGATCTGGCTGGTGAAGAAG





GGCAACAGCTACCCCAAGCTGTCCAAGTCTTACATTAACGAC





AAGGGCAAGGAGGTGCTGGTCCTGTGGGGCATCCACCACCCC





AGCACCAGCGCCGACCAACAGAGCCTGTACCAGAACGCCGA





CACCTACGTGTTCGTGGGCAGCAGCCGGTACAGCAAGAAGTT





CAAGCCCGAGATCGCCATCCGGCCCAAGGTGCGGGACCAGG





AGGGCCGGATGAACTACTACTGGACCCTGGTGGAGCCTGGCG





ACAAGATCACCTTCGAGGCCACCGGCAACCTGGTGGTGCCCC





GGTACGCCTTCGCCATGGAGCGGAACGCC




mRNA
AUGAAGGUGAAGCUUCUCGUGCUCUUAUGCACCUUCACCGC
540




CACCUACGCCGGCGUGGCUCCGCUUCACCUUGGCAAGUGCA





ACAUCGCCGGCUGGAUCUUGGGAAACCCCGAGUGCGAGAGC





UUGAGCACCGCCAGCAGCUGGAGCUACAUCGUGGAAACCCC





UAGCAGCGACAACGGCACCUGCUACCCCGGCGACUUCAUCG





ACUACGAGGAGCUGCGGGAGCAGCUGAGCAGCGUGAGCAGC





UUCGAGCGGUUCGAGAUCUUCCCCAAGACCAGCUCUUGGCC





CAACCACGACAGCAACAAGGGCGUGACCGCCGCCUGCCCUC





ACGCUGGCGCCAAGAGCUUCUACAAGAACCUGAUCUGGCUG





GUGAAGAAGGGCAACAGCUACCCCAAGCUGUCCAAGUCUUA





CAUUAACGACAAGGGCAAGGAGGUGCUGGUCCUGUGGGGC





AUCCACCACCCCAGCACCAGCGCCGACCAACAGAGCCUGUA





CCAGAACGCCGACACCUACGUGUUCGUGGGCAGCAGCCGGU





ACAGCAAGAAGUUCAAGCCCGAGAUCGCCAUCCGGCCCAAG





GUGCGGGACCAGGAGGGCCGGAUGAACUACUACUGGACCCU





GGUGGAGCCUGGCGACAAGAUCACCUUCGAGGCCACCGGCA





ACCUGGUGGUGCCCCGGUACGCCUUCGCCAUGGAGCGGAAC





GCC




Protein
MKVKLLVLLCTFTATYAGVAPLHLGKCNIAGWILGNPECESLST
559




ASSWSYIVETPSSDNGTCYPGDFIDYEELREQLSSVSSFERFEIFPK





TSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPKLS





KSYINDKGKEVLVLWGIHHPSTSADQQSLYQNADTYVFVGSSR





YSKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGNLV





VPRYAFAMERNA






FLHA_PR8
DNA
ATGAAGGCCAATTTGTTGGTCCTTCTATGTGCCCTAGCCGCCG
522




CCGACGCCGACACAATCTGCATCGGATATCACGCAAACAACA





GCACCGACACCGTGGATACGGTCTTGGAGAAGAACGTGACCG





TGACCCATTCCGTGAACCTTCTCGAGGATAGCCACAATGGCA





AGCTGTGTAGACTCAAGGGCATTGCCCCGCTGCAGCTGGGAA





AGTGCAATATTGCTGGCTGGCTGTTGGGCAACCCTGAGTGTG





ACCCTCTGTTACCAGTGAGATCTTGGAGCTATATCGTCGAAA





CCCCTAACAGCGAGAACGGCATATGCTACCCAGGCGACTTCA





TCGACTACGAGGAACTGCGCGAGCAGCTGAGCTCTGTGTCGA





GCTTCGAGCGGTTCGAGATCTTCCCTAAGGAATCTAGCTGGC





CTAATCATAACACAAATGGCGTTACTGCTGCCTGTAGCCACG





AGGGAAAGAGCAGTTTCTACCGGAATCTGCTGTGGCTGACAG





AGAAGGAGGGCTCCTACCCTAAGCTGAAGAATAGCTATGTGA





ACAAGAAGGGCAAGGAGGTGCTGGTGCTGTGGGGAATACAC





CACCCACCTAACTCGAAGGAGCAGCAGAATCTGTACCAGAAT





GAGAATGCCTACGTGTCCGTCGTGACCTCCAACTACAACCGG





CGGTTCACGCCTGAGATCGCCGAGAGGCCTAAGGTGAGGGAC





CAGGCCGGACGCATGAACTACTACTGGACCCTGCTGAAGCCT





GGCGATACAATCATCTTCGAGGCTAATGGAAACCTGATCGCG





CCAATGTACGCCTTCGCCCTGTCCAGAGGATTCGGCAGCGGC





ATCATCACATCCAACGCCTCCATGCACGAATGCAACACCAAG





TGCCAGACGCCTCTGGGAGCTATCAATAGCAGCTTGCCTTAC





CAGAATATCCACCCTGTGACCATTGGAGAGTGTCCAAAGTAC





GTGCGCAGCGCAAAGCTGCGGATGGTCACAGGCCTGCGGAAT





ATACCTTCTATCCAGAGCCGAGGCCTGTTCGGTGCCATTGCCG





GCTTCATCGAGGGTGGCTGGACCGGAATGATCGACGGCTGGT





ATGGATACCACCACCAGAATGAACAGGGCAGCGGCTACGCC





GCCGATCAGAAGTCCACCCAGAACGCAATCAATGGTATCACA





AACAAGGTGAACACTGTAATCGAGAAGATGAACATCCAATTC





ACAGCCGTGGGCAAGGAGTTCAATAAGCTGGAGAAGCGGAT





GGAGAACCTCAACAAGAAGGTGGACGACGGCTTCCTGGATAT





CTGGACCTACAACGCAGAGCTGCTGGTGTTGCTGGAGAACGA





GAGAACCCTCGACTTCCATGATAGCAACGTTAAGAACCTATA





CGAGAAGGTGAAGTCACAGCTGAAGAATAACGCCAAGGAGA





TTGGCAACGGCTGCTTCGAATTCTACCACAAGTGCGACAACG





AGTGTATGGAGAGCGTCCGGAATGGCACCTACGACTATCCTA





AGTATAGCGAGGAGAGCAAGCTTAATAGAGAGAAGGTCGAT





GGCGTGAAGCTGGAGTCAATGGGAATCTACCAGATCCTGGCT





ATTTATTCAACCGTGGCATCAAGTCTGGTGCTTCTGGTCAGCC





TGGGCGCCATCAGCTTCTGGATGTGCTCCAATGGCAGCCTGC





AATGCCGCATCTGCATA




mRNA
AUGAAGGCCAAUUUGUUGGUCCUUCUAUGUGCCCUAGCCGC
541




CGCCGACGCCGACACAAUCUGCAUCGGAUAUCACGCAAACA





ACAGCACCGACACCGUGGAUACGGUCUUGGAGAAGAACGUG





ACCGUGACCCAUUCCGUGAACCUUCUCGAGGAUAGCCACAA





UGGCAAGCUGUGUAGACUCAAGGGCAUUGCCCCGCUGCAGC





UGGGAAAGUGCAAUAUUGCUGGCUGGCUGUUGGGCAACCC





UGAGUGUGACCCUCUGUUACCAGUGAGAUCUUGGAGCUAU





AUCGUCGAAACCCCUAACAGCGAGAACGGCAUAUGCUACCC





AGGCGACUUCAUCGACUACGAGGAACUGCGCGAGCAGCUGA





GCUCUGUGUCGAGCUUCGAGCGGUUCGAGAUCUUCCCUAAG





GAAUCUAGCUGGCCUAAUCAUAACACAAAUGGCGUUACUGC





UGCCUGUAGCCACGAGGGAAAGAGCAGUUUCUACCGGAAUC





UGCUGUGGCUGACAGAGAAGGAGGGCUCCUACCCUAAGCUG





AAGAAUAGCUAUGUGAACAAGAAGGGCAAGGAGGUGCUGG





UGCUGUGGGGAAUACACCACCCACCUAACUCGAAGGAGCAG





CAGAAUCUGUACCAGAAUGAGAAUGCCUACGUGUCCGUCGU





GACCUCCAACUACAACCGGCGGUUCACGCCUGAGAUCGCCG





AGAGGCCUAAGGUGAGGGACCAGGCCGGACGCAUGAACUAC





UACUGGACCCUGCUGAAGCCUGGCGAUACAAUCAUCUUCGA





GGCUAAUGGAAACCUGAUCGCGCCAAUGUACGCCUUCGCCC





UGUCCAGAGGAUUCGGCAGCGGCAUCAUCACAUCCAACGCC





UCCAUGCACGAAUGCAACACCAAGUGCCAGACGCCUCUGGG





AGCUAUCAAUAGCAGCUUGCCUUACCAGAAUAUCCACCCUG





UGACCAUUGGAGAGUGUCCAAAGUACGUGCGCAGCGCAAA





GCUGCGGAUGGUCACAGGCCUGCGGAAUAUACCUUCUAUCC





AGAGCCGAGGCCUGUUCGGUGCCAUUGCCGGCUUCAUCGAG





GGUGGCUGGACCGGAAUGAUCGACGGCUGGUAUGGAUACC





ACCACCAGAAUGAACAGGGCAGCGGCUACGCCGCCGAUCAG





AAGUCCACCCAGAACGCAAUCAAUGGUAUCACAAACAAGGU





GAACACUGUAAUCGAGAAGAUGAACAUCCAAUUCACAGCCG





UGGGCAAGGAGUUCAAUAAGCUGGAGAAGCGGAUGGAGAA





CCUCAACAAGAAGGUGGACGACGGCUUCCUGGAUAUCUGGA





CCUACAACGCAGAGCUGCUGGUGUUGCUGGAGAACGAGAG





AACCCUCGACUUCCAUGAUAGCAACGUUAAGAACCUAUACG





AGAAGGUGAAGUCACAGCUGAAGAAUAACGCCAAGGAGAU





UGGCAACGGCUGCUUCGAAUUCUACCACAAGUGCGACAACG





AGUGUAUGGAGAGCGUCCGGAAUGGCACCUACGACUAUCCU





AAGUAUAGCGAGGAGAGCAAGCUUAAUAGAGAGAAGGUCG





AUGGCGUGAAGCUGGAGUCAAUGGGAAUCUACCAGAUCCU





GGCUAUUUAUUCAACCGUGGCAUCAAGUCUGGUGCUUCUG





GUCAGCCUGGGCGCCAUCAGCUUCUGGAUGUGCUCCAAUGG





CAGCCUGCAAUGCCGCAUCUGCAUA




Protein
MKANLLVLLCALAAADADTICIGYHANNSTDTVDTVLEKNVTV
560




THSVNLLEDSHNGKLCRLKGIAPLQLGKCNIAGWLLGNPECDPL





LPVRSWSYIVETPNSENGICYPGDFIDYEELREQLSSVSSFERFEIF





PKESSWPNHNTNGVTAACSHEGKSSFYRNLLWLTEKEGSYPKL





KNSYVNKKGKEVLVLWGIHHPPNSKEQQNLYQNENAYVSVVT





SNYNRRFTPEIAERPKVRDQAGRMNYYWTLLKPGDTIIFEANGN





LIAPMYAFALSRGFGSGIITSNASMHECNTKCQTPLGAINSSLPY





QNIHPVTIGECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGFIE





GGWTGMIDGWYGYHHQNEQGSGYAADQKSTQNAINGITNKVN





TVIEKMNIQFTAVGKEFNKLEKRMENLNKKVDDGFLDIWTYNA





ELLVLLENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGCFEF





YHKCDNECMESVRNGTYDYPKYSEESKLNREKVDGVKLESMGI





YQILAIYSTVASSLVLLVSLGAISFWMCSNGSLQCRICI






FLHA_Cal09
DNA
ATGAAGGCTATCTTGGTGGTGTTGTTGTACACATTCGCCACCG
523




CCAACGCCGACACCCTCTGCATCGGCTACCACGCGAACAATT





CAACCGACACCGTTGACACCGTCCTCGAGAAGAACGTGACCG





TGACTCATAGCGTCAACCTCCTCGAGGACAAGCATAACGGCA





AGCTCTGTAAGCTTAGAGGAGTGGCCCCTCTCCACCTGGGCA





AGTGTAACATTGCAGGCTGGATCCTGGGCAACCCTGAGTGCG





AGAGCCTGTCAACCGCTAGCAGCTGGAGCTACATCGTGGAAA





CCCCATCCAGCGATAACGGCACCTGCTACCCTGGCGATTTCA





TCGACTACGAGGAGCTGCGCGAGCAGTTGAGCAGCGTCTCCA





GCTTCGAGAGATTCGAGATCTTCCCTAAGACTAGCAGCTGGC





CTAATCATGACTCCAATAAGGGCGTGACGGCCGCCTGTCCTC





ACGCTGGAGCCAAGTCGTTCTACAAGAACCTGATCTGGCTGG





TAAAGAAGGGCAACAGCTACCCAAAGCTGAGCAAGTCCTAC





ATCAACGACAAGGGCAAGGAAGTGCTGGTGCTGTGGGGAAT





CCATCACCCAAGCACCTCTGCGGACCAGCAGTCTCTGTATCA





GAACGCCGACACCTATGTGTTCGTAGGCTCCTCCAGATACTC





CAAGAAGTTCAAGCCAGAGATTGCTATCCGCCCAAAGGTGCG





GGATCAAGAGGGTCGCATGAATTATTACTGGACCCTGGTCGA





GCCAGGCGATAAGATCACATTCGAAGCCACGGGAAATCTGGT





GGTGCCTAGATACGCTTTCGCCATGGAGAGAAACGCCGGCAG





CGGCATCATCATATCCGACACACCTGTGCACGACTGCAACAC





AACATGCCAGACGCCAAAGGGAGCCATCAACACATCTCTTCC





ATTCCAGAACATTCACCCAATCACAATCGGCAAGTGTCCAAA





GTACGTGAAGTCCACCAAGCTTAGACTGGCCACCGGCCTGCG





TAACATCCCTAGCATCCAGTCGAGAGGCCTCTTCGGCGCCAT





CGCCGGATTCATTGAAGGTGGCTGGACCGGCATGGTGGACGG





TTGGTATGGCTACCACCACCAGAACGAGCAGGGCAGCGGCTA





CGCCGCGGACCTGAAGTCCACCCAGAACGCTATTGACGAGAT





CACCAACAAGGTGAACAGCGTGATCGAGAAGATGAATACCC





AGTTCACCGCCGTCGGCAAGGAGTTCAACCATCTGGAGAAGA





GAATCGAGAACCTCAACAAGAAGGTCGACGACGGCTTCCTGG





ACATTTGGACTTACAACGCTGAGTTGTTGGTGCTTCTTGAGAA





TGAGCGGACCCTGGACTATCACGACTCAAATGTGAAGAACCT





GTACGAGAAGGTGAGATCCCAGCTGAAGAACAATGCTAAGG





AAATCGGCAACGGCTGCTTCGAGTTCTATCATAAGTGTGACA





ACACCTGCATGGAGTCTGTTAAGAACGGCACATACGACTACC





CGAAGTACTCTGAGGAGGCCAAGCTGAACCGAGAGGAGATA





GACGGCGTTAAGCTAGAAAGTACAAGGATCTACCAGATCCTT





GCCATCTACTCCACCGTGGCCTCCAGCCTGGTGTTGGTGGTGA





GCCTGGGCGCCATCAGCTTCTGGATGTGCAGTAACGGAAGCC





TACAGTGCCGAATCTGCATC




mRNA
AUGAAGGCUAUCUUGGUGGUGUUGUUGUACACAUUCGCCA
542




CCGCCAACGCCGACACCCUCUGCAUCGGCUACCACGCGAAC





AAUUCAACCGACACCGUUGACACCGUCCUCGAGAAGAACGU





GACCGUGACUCAUAGCGUCAACCUCCUCGAGGACAAGCAUA





ACGGCAAGCUCUGUAAGCUUAGAGGAGUGGCCCCUCUCCAC





CUGGGCAAGUGUAACAUUGCAGGCUGGAUCCUGGGCAACCC





UGAGUGCGAGAGCCUGUCAACCGCUAGCAGCUGGAGCUACA





UCGUGGAAACCCCAUCCAGCGAUAACGGCACCUGCUACCCU





GGCGAUUUCAUCGACUACGAGGAGCUGCGCGAGCAGUUGA





GCAGCGUCUCCAGCUUCGAGAGAUUCGAGAUCUUCCCUAAG





ACUAGCAGCUGGCCUAAUCAUGACUCCAAUAAGGGCGUGAC





GGCCGCCUGUCCUCACGCUGGAGCCAAGUCGUUCUACAAGA





ACCUGAUCUGGCUGGUAAAGAAGGGCAACAGCUACCCAAAG





CUGAGCAAGUCCUACAUCAACGACAAGGGCAAGGAAGUGCU





GGUGCUGUGGGGAAUCCAUCACCCAAGCACCUCUGCGGACC





AGCAGUCUCUGUAUCAGAACGCCGACACCUAUGUGUUCGUA





GGCUCCUCCAGAUACUCCAAGAAGUUCAAGCCAGAGAUUGC





UAUCCGCCCAAAGGUGCGGGAUCAAGAGGGUCGCAUGAAU





UAUUACUGGACCCUGGUCGAGCCAGGCGAUAAGAUCACAUU





CGAAGCCACGGGAAAUCUGGUGGUGCCUAGAUACGCUUUCG





CCAUGGAGAGAAACGCCGGCAGCGGCAUCAUCAUAUCCGAC





ACACCUGUGCACGACUGCAACACAACAUGCCAGACGCCAAA





GGGAGCCAUCAACACAUCUCUUCCAUUCCAGAACAUUCACC





CAAUCACAAUCGGCAAGUGUCCAAAGUACGUGAAGUCCACC





AAGCUUAGACUGGCCACCGGCCUGCGUAACAUCCCUAGCAU





CCAGUCGAGAGGCCUCUUCGGCGCCAUCGCCGGAUUCAUUG





AAGGUGGCUGGACCGGCAUGGUGGACGGUUGGUAUGGCUA





CCACCACCAGAACGAGCAGGGCAGCGGCUACGCCGCGGACC





UGAAGUCCACCCAGAACGCUAUUGACGAGAUCACCAACAAG





GUGAACAGCGUGAUCGAGAAGAUGAAUACCCAGUUCACCGC





CGUCGGCAAGGAGUUCAACCAUCUGGAGAAGAGAAUCGAG





AACCUCAACAAGAAGGUCGACGACGGCUUCCUGGACAUUUG





GACUUACAACGCUGAGUUGUUGGUGCUUCUUGAGAAUGAG





CGGACCCUGGACUAUCACGACUCAAAUGUGAAGAACCUGUA





CGAGAAGGUGAGAUCCCAGCUGAAGAACAAUGCUAAGGAA





AUCGGCAACGGCUGCUUCGAGUUCUAUCAUAAGUGUGACA





ACACCUGCAUGGAGUCUGUUAAGAACGGCACAUACGACUAC





CCGAAGUACUCUGAGGAGGCCAAGCUGAACCGAGAGGAGA





UAGACGGCGUUAAGCUAGAAAGUACAAGGAUCUACCAGAU





CCUUGCCAUCUACUCCACCGUGGCCUCCAGCCUGGUGUUGG





UGGUGAGCCUGGGCGCCAUCAGCUUCUGGAUGUGCAGUAAC





GGAAGCCUACAGUGCCGAAUCUGCAUC




Protein
MKAILVVLLYTFATANADTLCIGYHANNSTDTVDTVLEKNVTV
561




THSVNLLEDKHNGKLCKLRGVAPLHLGKCNIAGWILGNPECESL





STASSWSYIVETPSSDNGTCYPGDFIDYEELREQLSSVSSFERFEIF





PKTSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPK





LSKSYINDKGKEVLVLWGIHHPSTSADQQSLYQNADTYVFVGSS





RYSKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGNL





VVPRYAFAMERNAGSGIIISDTPVHDCNTTCQTPKGAINTSLPFQ





NIHPITIGKCPKYVKSTKLRLATGLRNIPSIQSRGLFGAIAGFIEGG





WTGMVDGWYGYHHQNEQGSGYAADLKSTQNAIDEITNKVNSV





IEKMNTQFTAVGKEFNHLEKRIENLNKKVDDGFLDIWTYNAELL





VLLENERTLDYHDSNVKNLYEKVRSQLKNNAKEIGNGCFEFYH





KCDNTCMESVKNGTYDYPKYSEEAKLNREEIDGVKLESTRIYQI





LAIYSTVASSLVLVVSLGAISFWMCSNGSLQCRICI






eH1HA_d5
Protein
METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDTVDTVLEKNV
562


v1

TVTHSVNLLEDSHNGKLCRLKGIAPLQLGKCNIAGWLLGNPECD





PLPPMKSWSYIVETPNSENGICYPGDFIDYEELREQLSSVSSFERF





EIFPKGSSWPNHNTNGVTAACSHEGKNSFYRNLLWLTKKEGLY





PNLENSYVNKKEKEVLVLWGIHHPSNNKEQQNLYQNENAYVSV





VTSNYNRRFTPEIAERPKVRDQAGRMNYYWTLLKPGDTIIFEAN





GNLIAPMYAFALSRGFGSGIITSNASMHECNTKCQTPLGAINSSL





PYQNIHPVTIGECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGF





IEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQNAINGITNK





VNTVIEKMNIQFTAVGKEFNKLEKRMENLNKKVDDGFLDIWTY





NAELLVLLENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGC





FEFYHKCDNECMESVRNGTYDYPKYSEESKLNREKVDGVKLES





MGIGSAGSAGYIPEAPRDGQAYVRKDGEWVLLSTFL






eH1HA_d5
Protein
METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDTVDTVLEKNV
563


v2

TVTHSVNLLEDSHNGKLCRLKG1APLQLGKCN1AGWLLGNPECD





PLPPMKSWSYIVETPNSENGICYPGDFIDYEELREQLSSVSSFERF





EIFPKGSSWPNHTTNGVTAACSHEGKNSFYRNLLWLTKKEGSYP





NLKNSYVNKKEKEVLVLWGIHHPSNSKEQQNLYQNENAHVSV





VTSNYNRRFTPEIAERPKVRDQAGRMNYYWTLLKPGDTIIFEAD





GNLIAPMYAFALSRGFGSGIITSNASMHECNTKCQTPLGAINSSL





PYQNIHPVTIGECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGF





IEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQNAINGITNK





VNTVIEKMNIQFTAVGKEFNKLEKRMENLNKKVDDGFLDIWTY





NAELLVLLENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGC





FEFYHKCDNECMESVRNGTYDYPKYSEESKLNREKVDGVKLES





MGIGSAGSAGYIPEAPRDGQAYVRKDGEWVLLSTFL






eH1HA_d5
Protein
METPAQLLFLLLLWLPDTTGDTICIGYFIANNSTDTVDTVLEKNV
564


v3

TVTHSVNLLEDSHNGKLCRLKGIAPLQLGKCNIAGWLLGNPECD





PLPPMKSWSYIVETPNSENGICYPGDFIDYEELREQLSSVSSFERF





EIFPKGSSWPDHNTNGVTAACSHEGKNSFYRNLLWLTEKKGSYP





NLKNPYVNKKEKEVLVLWGIHHPSNSKEQQNLYRNENAYVSV





VTSNYNRRFTPEIAERPKVRDQAGRMNYYWTLLKPGDTIIFEAN





GNLIAPMYAFALSRGFGSGIITSNASMHECNTKCQTPLGAINSSL





PYQNIHPVTIGECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGF





IEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQNAINGITNK





VNTVIEKMNIQFTAVGKEFNKLEKRMENLNKKVDDGFLDIWTY





NAELLVLLENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGC





FEFYHKCDNECMESVRNGTYDYPKYSEESKLNREKVDGVKLES





MGIGSAGSAGYIPEAPRDGQAYVRKDGEWVLLSTFL






eH1HA_d5
Protein
METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDTVDTVLEKNV
565


v4

TVTHSVNLLEDSHNGKLCKLKGIAPLQLGKCNIAGWLLGNPGC





DPLLPVGSWSYIVETPNSENGICYPGDFIDYEELREQLSSVSSFER





FKIFPKESSWPDHNTNGVTAACSHEGKNSFYRNLLWLTKKESSY





PNLENSYVNKKRKEVLVLWGIHHPSNSKEQQNLYQNENAYVSV





VTSNYNRRFTPEIAERPKVKGQAGRMNYYWTLLKPGDTIIFEAN





GNLIAPMYAFALSRGFGSGIITSNASMHECNTKCQTPLGAINSSL





PYQNIHPVTIGECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGF





IEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQNAINGITNK





VNTVIEKMNIQFTAVGKEFNKLEKRMENLNKKVDDGFLDIWTY





NAELLVLLENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGC





FEFYHKCDNECMESVRNGTYDYPKYSEESKLNREKVDGVKLES





MGIGSAGSAGYIPEAPRDGQAYVRKDGEWVLLSTFL






eH1HA_d5
mRNA
AUGGAGACGCCUGCUCAGCUGCUCUUUCUGCUGCUCCUGUG
566


v1

GUUGCCCGAUACCACUGGGGACACUAUCUGUAUCGGAUACC





ACGCCAACAACUCAACCGAUACCGUGGAUACUGUCCUCGAA





AAGAAUGUGACCGUUACACAUUCAGUAAAUUUGUUAGAGG





AUUCUCACAAUGGGAAGCUGUGUCGACUGAAGGGGAUCGC





UCCCCUGCAACUGGGGAAGUGCAACAUCGCUGGAUGGUUGC





UCGGCAACCCGGAAUGCGAUCCGCUGCCACCCAUGAAGAGU





UGGAGCUAUAUUGUCGAGACCCCUAACUCAGAGAACGGUA





UAUGCUACCCUGGAGAUUUUAUCGAUUACGAAGAGCUGCG





GGAACAGCUGAGCAGCGUCUCCAGUUUCGAACGGUUUGAA





AUAUUCCCCAAGGGCAGUUCCUGGCCCAAUCACAACACUAA





UGGCGUCACCGCCGCCUGCUCACACGAGGGUAAGAACUCUU





UUUACCGCAAUCUGCUUUGGCUUACUAAGAAGGAAGGACU





GUACCCGAAUCUGGAGAACAGUUACGUCAACAAGAAAGAG





AAAGAGGUCCUGGUGCUGUGGGGAAUUCACCACCCUUCCAA





UAACAAGGAACAGCAGAAUCUGUACCAAAACGAAAAUGCU





UACGUGAGUGUGGUGACCUCGAACUAUAAUAGACGAUUCA





CACCUGAGAUUGCCGAGCGUCCCAAAGUUAGGGACCAAGCC





GGUAGGAUGAACUACUACUGGACUCUCCUGAAGCCCGGUGA





CACCAUUAUCUUCGAGGCCAAUGGUAAUCUGAUCGCCCCUA





UGUACGCUUUCGCACUGUCACGCGGGUUCGGAUCUGGGAUA





AUUACUUCGAACGCUAGCAUGCAUGAGUGUAAUACCAAGU





GCCAGACCCCACUUGGAGCAAUCAAUUCCAGCCUACCUUAU





CAGAAUAUUCAUCCCGUGACCAUCGGAGAAUGCCCAAAGUA





CGUUAGGUCCGCUAAACUGAGGAUGGUGACUGGCUUGAGG





AACAUACCAUCUAUCCAAUCUAGGGGCCUGUUUGGCGCUAU





UGCCGGGUUCAUCGAGGGUGGCUGGACAGGCAUGAUUGAC





GGGUGGUACGGUUACCACCACCAGAACGAGCAGGGAUCCGG





CUAUGCAGCUGACCAGAAGUCAACCCAGAACGCAAUCAACG





GCAUCACAAAUAAGGUCAAUACUGUGAUCGAAAAGAUGAA





CAUCCAAUUCACUGCCGUGGGCAAGGAGUUUAAUAAGCUCG





AGAAGCGCAUGGAAAAUCUGAACAAAAAAGUGGACGAUGG





CUUCCUGGAUAUAUGGACUUACAACGCCGAGCUCCUUGUGC





UUCUGGAGAACGAACGUACCUUGGACUUUCAUGAUAGUAA





CGUCAAGAAUUUGUACGAGAAGGUUAAAUCCCAGCUGAAG





AACAAUGCCAAGGAAAUCGGCAACGGCUGUUUUGAAUUUU





ACCAUAAAUGCGACAAUGAGUGCAUGGAAUCCGUACGCAA





UGGGACAUACGAUUACCCUAAAUACUCCGAGGAAAGCAAGC





UCAACCGAGAAAAAGUGGACGGCGUCAAGCUCGAAUCAAU





GGGUAUUGGCAGUGCCGGAUCCGCCGGGUAUAUCCCCGAGG





CCCCUAGAGACGGCCAAGCCUAUGUGCGGAAAGACGGCGAA





UGGGUUCUGCUAUCCACCUUCUUA






eH1HA_d5
5′ UTR
GGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAG
574


v1

AGCCACC






eH1HA_d5
3′ UTR
UGAUAAUAGGCUGGAGCCUCGGUGGCCAUGCUUCUUGCCCC
575


v1

UUGGGCCUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUA





CCCCCGUGGUCUUUGAAUAAAGUCUGAGUGGGCGGC






eH1HA_d5
DNA
ATGGAGACGCCTGCTCAGCTGCTCTTTCTGCTGCTCCTGTGGT
570


v1

TGCCCGATACCACTGGGGACACTATCTGTATCGGATACCACG





CCAACAACTCAACCGATACCGTGGATACTGTCCTCGAAAAGA





ATGTGACCGTTACACATTCAGTAAATTTGTTAGAGGATTCTCA





CAATGGGAAGCTGTGTCGACTGAAGGGGATCGCTCCCCTGCA





ACTGGGGAAGTGCAACATCGCTGGATGGTTGCTCGGCAACCC





GGAATGCGATCCGCTGCCACCCATGAAGAGTTGGAGCTATAT





TGTCGAGACCCCTAACTCAGAGAACGGTATATGCTACCCTGG





AGATTTTATCGATTACGAAGAGCTGCGGGAACAGCTGAGCAG





CGTCTCCAGTTTCGAACGGTTTGAAATATTCCCCAAGGGCAG





TTCCTGGCCCAATCACAACACTAATGGCGTCACCGCCGCCTG





CTCACACGAGGGTAAGAACTCTTTTTACCGCAATCTGCTTTGG





CTTACTAAGAAGGAAGGACTGTACCCGAATCTGGAGAACAGT





TACGTCAACAAGAAAGAGAAAGAGGTCCTGGTGCTGTGGGG





AATTCACCACCCTTCCAATAACAAGGAACAGCAGAATCTGTA





CCAAAACGAAAATGCTTACGTGAGTGTGGTGACCTCGAACTA





TAATAGACGATTCACACCTGAGATTGCCGAGCGTCCCAAAGT





TAGGGACCAAGCCGGTAGGATGAACTACTACTGGACTCTCCT





GAAGCCCGGTGACACCATTATCTTCGAGGCCAATGGTAATCT





GATCGCCCCTATGTACGCTTTCGCACTGTCACGCGGGTTCGGA





TCTGGGATAATTACTTCGAACGCTAGCATGCATGAGTGTAAT





ACCAAGTGCCAGACCCCACTTGGAGCAATCAATTCCAGCCTA





CCTTATCAGAATATTCATCCCGTGACCATCGGAGAATGCCCA





AAGTACGTTAGGTCCGCTAAACTGAGGATGGTGACTGGCTTG





AGGAACATACCATCTATCCAATCTAGGGGCCTGTTTGGCGCT





ATTGCCGGGTTCATCGAGGGTGGCTGGACAGGCATGATTGAC





GGGTGGTACGGTTACCACCACCAGAACGAGCAGGGATCCGG





CTATGCAGCTGACCAGAAGTCAACCCAGAACGCAATCAACGG





CATCACAAATAAGGTCAATACTGTGATCGAAAAGATGAACAT





CCAATTCACTGCCGTGGGCAAGGAGTTTAATAAGCTCGAGAA





GCGCATGGAAAATCTGAACAAAAAAGTGGACGATGGCTTCCT





GGATATATGGACTTACAACGCCGAGCTCCTTGTGCTTCTGGA





GAACGAACGTACCTTGGACTTTCATGATAGTAACGTCAAGAA





TTTGTACGAGAAGGTTAAATCCCAGCTGAAGAACAATGCCAA





GGAAATCGGCAACGGCTGTTTTGAATTTTACCATAAATGCGA





CAATGAGTGCATGGAATCCGTACGCAATGGGACATACGATTA





CCCTAAATACTCCGAGGAAAGCAAGCTCAACCGAGAAAAAG





TGGACGGCGTCAAGCTCGAATCAATGGGTATTGGCAGTGCCG





GATCCGCCGGGTATATCCCCGAGGCCCCTAGAGACGGCCAAG





CCTATGTGCGGAAAGACGGCGAATGGGTTCTGCTATCCACCT





TCTTA






eH1HA_d5
mRNA
AUGGAGACGCCUGCUCAGCUGCUCUUUCUGCUGCUCCUGUG
567


v2

GUUGCCCGAUACCACUGGGGACACUAUCUGUAUCGGAUACC





ACGCCAACAACUCAACCGAUACCGUGGAUACUGUCCUCGAA





AAGAAUGUGACCGUUACACAUUCAGUAAAUUUGUUAGAGG





AUUCUCACAAUGGGAAGCUGUGUCGACUGAAGGGGAUCGC





UCCCCUGCAACUGGGGAAGUGCAACAUCGCUGGAUGGUUGC





UCGGCAACCCGGAAUGCGAUCCGCUGCCACCCAUGAAGAGU





UGGAGCUAUAUUGUCGAGACCCCUAACUCAGAGAACGGUA





UAUGCUACCCUGGAGAUUUUAUCGAUUACGAAGAGCUGCG





GGAACAGCUGAGCAGCGUCUCCAGUUUCGAACGGUUUGAA





AUAUUCCCCAAGGGCAGUUCCUGGCCCAAUCACACCACUAA





UGGCGUCACCGCCGCCUGCUCACACGAGGGUAAGAACUCUU





UUUACCGCAAUCUGCUUUGGCUUACUAAGAAGGAAGGAAG





UUACCCGAAUCUGAAAAACAGUUACGUCAACAAGAAAGAG





AAAGAGGUCCUGGUGCUGUGGGGAAUUCACCACCCUUCCAA





UUCGAAGGAACAGCAGAAUCUGUACCAAAACGAAAAUGCU





CACGUGAGUGUGGUGACCUCGAACUAUAAUAGACGAUUCA





CACCUGAGAUUGCCGAGCGUCCCAAAGUUAGGGACCAAGCC





GGUAGGAUGAACUACUACUGGACUCUCCUGAAGCCCGGUGA





CACCAUUAUCUUCGAGGCCGACGGUAAUCUGAUCGCCCCUA





UGUACGCUUUCGCACUGUCACGCGGGUUCGGAUCUGGGAUA





AUUACUUCGAACGCUAGCAUGCAUGAGUGUAAUACCAAGU





GCCAGACCCCACUUGGAGCAAUCAAUUCCAGCCUACCUUAU





CAGAAUAUUCAUCCCGUGACCAUCGGAGAAUGCCCAAAGUA





CGUUAGGUCCGCUAAACUGAGGAUGGUGACUGGCUUGAGG





AACAUACCAUCUAUCCAAUCUAGGGGCCUGUUUGGCGCUAU





UGCCGGGUUCAUCGAGGGUGGCUGGACAGGCAUGAUUGAC





GGGUGGUACGGUUACCACCACCAGAACGAGCAGGGAUCCGG





CUAUGCAGCUGACCAGAAGUCAACCCAGAACGCAAUCAACG





GCAUCACAAAUAAGGUCAAUACUGUGAUCGAAAAGAUGAA





CAUCCAAUUCACUGCCGUGGGCAAGGAGUUUAAUAAGCUCG





AGAAGCGCAUGGAAAAUCUGAACAAAAAAGUGGACGAUGG





CUUCCUGGAUAUAUGGACUUACAACGCCGAGCUCCUUGUGC





UUCUGGAGAACGAACGUACCUUGGACUUUCAUGAUAGUAA





CGUCAAGAAUUUGUACGAGAAGGUUAAAUCCCAGCUGAAG





AACAAUGCCAAGGAAAUCGGCAACGGCUGUUUUGAAUUUU





ACCAUAAAUGCGACAAUGAGUGCAUGGAAUCCGUACGCAA





UGGGACAUACGAUUACCCUAAAUACUCCGAGGAAAGCAAGC





UCAACCGAGAAAAAGUGGACGGCGUCAAGCUCGAAUCAAU





GGGUAUUGGCAGUGCCGGAUCCGCCGGGUAUAUCCCCGAGG





CCCCUAGAGACGGCCAAGCCUAUGUGCGGAAAGACGGCGAA





UGGGUUCUGCUAUCCACCUUCUUA






eH1HA_d5
5′ UTR
GGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAG
574


v2

AGCCACC






eH1HA_d5
3′ UTR
UGAUAAUAGGCUGGAGCCUCGGUGGCCAUGCUUCUUGCCCC
575


v2

UUGGGCCUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUA





CCCCCGUGGUCUUUGAAUAAAGUCUGAGUGGGCGGC






eH1HA_d5
DNA
ATGGAGACGCCTGCTCAGCTGCTCTTTCTGCTGCTCCTGTGGT
571


v2

TGCCCGATACCACTGGGGACACTATCTGTATCGGATACCACG





CCAACAACTCAACCGATACCGTGGATACTGTCCTCGAAAAGA





ATGTGACCGTTACACATTCAGTAAATTTGTTAGAGGATTCTCA





CAATGGGAAGCTGTGTCGACTGAAGGGGATCGCTCCCCTGCA





ACTGGGGAAGTGCAACATCGCTGGATGGTTGCTCGGCAACCC





GGAATGCGATCCGCTGCCACCCATGAAGAGTTGGAGCTATAT





TGTCGAGACCCCTAACTCAGAGAACGGTATATGCTACCCTGG





AGATTTTATCGATTACGAAGAGCTGCGGGAACAGCTGAGCAG





CGTCTCCAGTTTCGAACGGTTTGAAATATTCCCCAAGGGCAG





TTCCTGGCCCAATCACACCACTAATGGCGTCACCGCCGCCTG





CTCACACGAGGGTAAGAACTCTTTTTACCGCAATCTGCTTTGG





CTTACTAAGAAGGAAGGAAGTTACCCGAATCTGAAAAACAGT





TACGTCAACAAGAAAGAGAAAGAGGTCCTGGTGCTGTGGGG





AATTCACCACCCTTCCAATTCGAAGGAACAGCAGAATCTGTA





CCAAAACGAAAATGCTCACGTGAGTGTGGTGACCTCGAACTA





TAATAGACGATTCACACCTGAGATTGCCGAGCGTCCCAAAGT





TAGGGACCAAGCCGGTAGGATGAACTACTACTGGACTCTCCT





GAAGCCCGGTGACACCATTATCTTCGAGGCCGACGGTAATCT





GATCGCCCCTATGTACGCTTTCGCACTGTCACGCGGGTTCGGA





TCTGGGATAATTACTTCGAACGCTAGCATGCATGAGTGTAAT





ACCAAGTGCCAGACCCCACTTGGAGCAATCAATTCCAGCCTA





CCTTATCAGAATATTCATCCCGTGACCATCGGAGAATGCCCA





AAGTACGTTAGGTCCGCTAAACTGAGGATGGTGACTGGCTTG





AGGAACATACCATCTATCCAATCTAGGGGCCTGTTTGGCGCT





ATTGCCGGGTTCATCGAGGGTGGCTGGACAGGCATGATTGAC





GGGTGGTACGGTTACCACCACCAGAACGAGCAGGGATCCGG





CTATGCAGCTGACCAGAAGTCAACCCAGAACGCAATCAACGG





CATCACAAATAAGGTCAATACTGTGATCGAAAAGATGAACAT





CCAATTCACTGCCGTGGGCAAGGAGTTTAATAAGCTCGAGAA





GCGCATGGAAAATCTGAACAAAAAAGTGGACGATGGCTTCCT





GGATATATGGACTTACAACGCCGAGCTCCTTGTGCTTCTGGA





GAACGAACGTACCTTGGACTTTCATGATAGTAACGTCAAGAA





TTTGTACGAGAAGGTTAAATCCCAGCTGAAGAACAATGCCAA





GGAAATCGGCAACGGCTGTTTTGAATTTTACCATAAATGCGA





CAATGAGTGCATGGAATCCGTACGCAATGGGACATACGATTA





CCCTAAATACTCCGAGGAAAGCAAGCTCAACCGAGAAAAAG





TGGACGGCGTCAAGCTCGAATCAATGGGTATTGGCAGTGCCG





GATCCGCCGGGTATATCCCCGAGGCCCCTAGAGACGGCCAAG





CCTATGTGCGGAAAGACGGCGAATGGGTTCTGCTATCCACCT





TCTTA






eH1HA_d5
mRNA
AUGGAGACGCCUGCUCAGCUGCUCUUUCUGCUGCUCCUGUG
568


v3

GUUGCCCGAUACCACUGGGGACACUAUCUGUAUCGGAUACC





ACGCCAACAACUCAACCGAUACCGUGGAUACUGUCCUCGAA





AAGAAUGUGACCGUUACACAUUCAGUAAAUUUGUUAGAGG





AUUCUCACAAUGGGAAGCUGUGUCGACUGAAGGGGAUCGC





UCCCCUGCAACUGGGGAAGUGCAACAUCGCUGGAUGGUUGC





UCGGCAACCCGGAAUGCGAUCCGCUGCCACCCAUGAAGAGU





UGGAGCUAUAUUGUCGAGACCCCUAACUCAGAGAACGGUA





UAUGCUACCCUGGAGAUUUUAUCGAUUACGAAGAGCUGCG





GGAACAGCUGAGCAGCGUCUCCAGUUUCGAACGGUUUGAA





AUAUUCCCCAAGGGCAGUUCCUGGCCCGACCACAACACUAA





UGGCGUCACCGCCGCCUGCUCACACGAGGGUAAGAACUCUU





UUUACCGCAAUCUGCUUUGGCUUACUGAGAAGAAGGGAAG





UUACCCGAAUCUGAAAAACCCCUACGUCAACAAGAAAGAGA





AAGAGGUCCUGGUGCUGUGGGGAAUUCACCACCCUUCCAAU





UCGAAGGAACAGCAGAAUCUGUACAGAAACGAAAAUGCUU





ACGUGAGUGUGGUGACCUCGAACUAUAAUAGACGAUUCAC





ACCUGAGAUUGCCGAGCGUCCCAAAGUUAGGGACCAAGCCG





GUAGGAUGAACUACUACUGGACUCUCCUGAAGCCCGGUGAC





ACCAUUAUCUUCGAGGCCAAUGGUAAUCUGAUCGCCCCUAU





GUACGCUUUCGCACUGUCACGCGGGUUCGGAUCUGGGAUAA





UUACUUCGAACGCUAGCAUGCAUGAGUGUAAUACCAAGUG





CCAGACCCCACUUGGAGCAAUCAAUUCCAGCCUACCUUAUC





AGAAUAUUCAUCCCGUGACCAUCGGAGAAUGCCCAAAGUAC





GUUAGGUCCGCUAAACUGAGGAUGGUGACUGGCUUGAGGA





ACAUACCAUCUAUCCAAUCUAGGGGCCUGUUUGGCGCUAUU





GCCGGGUUCAUCGAGGGUGGCUGGACAGGCAUGAUUGACG





GGUGGUACGGUUACCACCACCAGAACGAGCAGGGAUCCGGC





UAUGCAGCUGACCAGAAGUCAACCCAGAACGCAAUCAACGG





CAUCACAAAUAAGGUCAAUACUGUGAUCGAAAAGAUGAAC





AUCCAAUUCACUGCCGUGGGCAAGGAGUUUAAUAAGCUCG





AGAAGCGCAUGGAAAAUCUGAACAAAAAAGUGGACGAUGG





CUUCCUGGAUAUAUGGACUUACAACGCCGAGCUCCUUGUGC





UUCUGGAGAACGAACGUACCUUGGACUUUCAUGAUAGUAA





CGUCAAGAAUUUGUACGAGAAGGUUAAAUCCCAGCUGAAG





AACAAUGCCAAGGAAAUCGGCAACGGCUGUUUUGAAUUUU





ACCAUAAAUGCGACAAUGAGUGCAUGGAAUCCGUACGCAA





UGGGACAUACGAUUACCCUAAAUACUCCGAGGAAAGCAAGC





UCAACCGAGAAAAAGUGGACGGCGUCAAGCUCGAAUCAAU





GGGUAUUGGCAGUGCCGGAUCCGCCGGGUAUAUCCCCGAGG





CCCCUAGAGACGGCCAAGCCUAUGUGCGGAAAGACGGCGAA





UGGGUUCUGCUAUCCACCUUCUUA






eH1HA_d5
5′ UTR
GGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAG
574


v3

AGCCACC






eH1HA_d5
3′ UTR
UGAUAAUAGGCUGGAGCCUCGGUGGCCAUGCUUCUUGCCCC
575


v3

UUGGGCCUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUA





CCCCCGUGGUCUUUGAAUAAAGUCUGAGUGGGCGGC






eH1HA_d5
DNA
ATGGAGACGCCTGCTCAGCTGCTCTTTCTGCTGCTCCTGTGGT
572


v3

TGCCCGATACCACTGGGGACACTATCTGTATCGGATACCACG





CCAACAACTCAACCGATACCGTGGATACTGTCCTCGAAAAGA





ATGTGACCGTTACACATTCAGTAAATTTGTTAGAGGATTCTCA





CAATGGGAAGCTGTGTCGACTGAAGGGGATCGCTCCCCTGCA





ACTGGGGAAGTGCAACATCGCTGGATGGTTGCTCGGCAACCC





GGAATGCGATCCGCTGCCACCCATGAAGAGTTGGAGCTATAT





TGTCGAGACCCCTAACTCAGAGAACGGTATATGCTACCCTGG





AGATTTTATCGATTACGAAGAGCTGCGGGAACAGCTGAGCAG





CGTCTCCAGTTTCGAACGGTTTGAAATATTCCCCAAGGGCAG





TTCCTGGCCCGACCACAACACTAATGGCGTCACCGCCGCCTG





CTCACACGAGGGTAAGAACTCTTTTTACCGCAATCTGCTTTGG





CTTACTGAGAAGAAGGGAAGTTACCCGAATCTGAAAAACCCC





TACGTCAACAAGAAAGAGAAAGAGGTCCTGGTGCTGTGGGG





AATTCACCACCCTTCCAATTCGAAGGAACAGCAGAATCTGTA





CAGAAACGAAAATGCTTACGTGAGTGTGGTGACCTCGAACTA





TAATAGACGATTCACACCTGAGATTGCCGAGCGTCCCAAAGT





TAGGGACCAAGCCGGTAGGATGAACTACTACTGGACTCTCCT





GAAGCCCGGTGACACCATTATCTTCGAGGCCAATGGTAATCT





GATCGCCCCTATGTACGCTTTCGCACTGTCACGCGGGTTCGGA





TCTGGGATAATTACTTCGAACGCTAGCATGCATGAGTGTAAT





ACCAAGTGCCAGACCCCACTTGGAGCAATCAATTCCAGCCTA





CCTTATCAGAATATTCATCCCGTGACCATCGGAGAATGCCCA





AAGTACGTTAGGTCCGCTAAACTGAGGATGGTGACTGGCTTG





AGGAACATACCATCTATCCAATCTAGGGGCCTGTTTGGCGCT





ATTGCCGGGTTCATCGAGGGTGGCTGGACAGGCATGATTGAC





GGGTGGTACGGTTACCACCACCAGAACGAGCAGGGATCCGG





CTATGCAGCTGACCAGAAGTCAACCCAGAACGCAATCAACGG





CATCACAAATAAGGTCAATACTGTGATCGAAAAGATGAACAT





CCAATTCACTGCCGTGGGCAAGGAGTTTAATAAGCTCGAGAA





GCGCATGGAAAATCTGAACAAAAAAGTGGACGATGGCTTCCT





GGATATATGGACTTACAACGCCGAGCTCCTTGTGCTTCTGGA





GAACGAACGTACCTTGGACTTTCATGATAGTAACGTCAAGAA





TTTGTACGAGAAGGTTAAATCCCAGCTGAAGAACAATGCCAA





GGAAATCGGCAACGGCTGTTTTGAATTTTACCATAAATGCGA





CAATGAGTGCATGGAATCCGTACGCAATGGGACATACGATTA





CCCTAAATACTCCGAGGAAAGCAAGCTCAACCGAGAAAAAG





TGGACGGCGTCAAGCTCGAATCAATGGGTATTGGCAGTGCCG





GATCCGCCGGGTATATCCCCGAGGCCCCTAGAGACGGCCAAG





CCTATGTGCGGAAAGACGGCGAATGGGTTCTGCTATCCACCT





TCTTA






eH1HA_d5
mRNA
AUGGAGACGCCUGCUCAGCUGCUCUUUCUGCUGCUCCUGUG
569


v4

GUUGCCCGAUACCACUGGGGACACUAUCUGUAUCGGAUACC





ACGCCAACAACUCAACCGAUACCGUGGAUACUGUCCUCGAA





AAGAAUGUGACCGUUACACAUUCAGUAAAUUUGUUAGAGG





AUUCUCACAAUGGGAAGCUGUGUAAGCUGAAGGGGAUCGC





UCCCCUGCAACUGGGGAAGUGCAACAUCGCUGGAUGGUUGC





UCGGCAACCCGGGCUGCGAUCCGCUGCUGCCCGUUGGCAGU





UGGAGCUAUAUUGUCGAGACCCCUAACUCAGAGAACGGUA





UAUGCUACCCUGGAGAUUUUAUCGAUUACGAAGAGCUGCG





GGAACAGCUGAGCAGCGUCUCCAGUUUCGAACGGUUUAAG





AUAUUCCCCAAGGAGAGUUCCUGGCCCGACCACAACACUAA





UGGCGUCACCGCCGCCUGCUCACACGAGGGUAAGAACUCUU





UUUACCGCAAUCUGCUUUGGCUUACUAAGAAGGAAAGCAG





UUACCCGAAUCUGGAGAACAGUUACGUCAACAAGAAACGG





AAAGAGGUCCUGGUGCUGUGGGGAAUUCACCACCCUUCCAA





UUCGAAGGAACAGCAGAAUCUGUACCAAAACGAAAAUGCU





UACGUGAGUGUGGUGACCUCGAACUAUAAUAGACGAUUCA





CACCUGAGAUUGCCGAGCGUCCCAAAGUUAAGGGCCAAGCC





GGUAGGAUGAACUACUACUGGACUCUCCUGAAGCCCGGUGA





CACCAUUAUCUUCGAGGCCAAUGGUAAUCUGAUCGCCCCUA





UGUACGCUUUCGCACUGUCACGCGGGUUCGGAUCUGGGAUA





AUUACUUCGAACGCUAGCAUGCAUGAGUGUAAUACCAAGU





GCCAGACCCCACUUGGAGCAAUCAAUUCCAGCCUACCUUAU





CAGAAUAUUCAUCCCGUGACCAUCGGAGAAUGCCCAAAGUA





CGUUAGGUCCGCUAAACUGAGGAUGGUGACUGGCUUGAGG





AACAUACCAUCUAUCCAAUCUAGGGGCCUGUUUGGCGCUAU





UGCCGGGUUCAUCGAGGGUGGCUGGACAGGCAUGAUUGAC





GGGUGGUACGGUUACCACCACCAGAACGAGCAGGGAUCCGG





CUAUGCAGCUGACCAGAAGUCAACCCAGAACGCAAUCAACG





GCAUCACAAAUAAGGUCAAUACUGUGAUCGAAAAGAUGAA





CAUCCAAUUCACUGCCGUGGGCAAGGAGUUUAAUAAGCUCG





AGAAGCGCAUGGAAAAUCUGAACAAAAAAGUGGACGAUGG





CUUCCUGGAUAUAUGGACUUACAACGCCGAGCUCCUUGUGC





UUCUGGAGAACGAACGUACCUUGGACUUUCAUGAUAGUAA





CGUCAAGAAUUUGUACGAGAAGGUUAAAUCCCAGCUGAAG





AACAAUGCCAAGGAAAUCGGCAACGGCUGUUUUGAAUUUU





ACCAUAAAUGCGACAAUGAGUGCAUGGAAUCCGUACGCAA





UGGGACAUACGAUUACCCUAAAUACUCCGAGGAAAGCAAGC





UCAACCGAGAAAAAGUGGACGGCGUCAAGCUCGAAUCAAU





GGGUAUUGGCAGUGCCGGAUCCGCCGGGUAUAUCCCCGAGG





CCCCUAGAGACGGCCAAGCCUAUGUGCGGAAAGACGGCGAA





UGGGUUCUGCUAUCCACCUUCUUA






eH1HA_d5
5′ UTR
GGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAG
574


v4

AGCCACC






eH1HA_d5
3′ UTR
UGAUAAUAGGCUGGAGCCUCGGUGGCCAUGCUUCUUGCCCC
575


v4

UUGGGCCUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUA





CCCCCGUGGUCUUUGAAUAAAGUCUGAGUGGGCGGC






eH1HA_d5
DNA
ATGGAGACGCCTGCTCAGCTGCTCTTTCTGCTGCTCCTGTGGT
573


v4

TGCCCGATACCACTGGGGACACTATCTGTATCGGATACCACG





CCAACAACTCAACCGATACCGTGGATACTGTCCTCGAAAAGA





ATGTGACCGTTACACATTCAGTAAATTTGTTAGAGGATTCTCA





CAATGGGAAGCTGTGTAAGCTGAAGGGGATCGCTCCCCTGCA





ACTGGGGAAGTGCAACATCGCTGGATGGTTGCTCGGCAACCC





GGGCTGCGATCCGCTGCTGCCCGTTGGCAGTTGGAGCTATAT





TGTCGAGACCCCTAACTCAGAGAACGGTATATGCTACCCTGG





AGATTTTATCGATTACGAAGAGCTGCGGGAACAGCTGAGCAG





CGTCTCCAGTTTCGAACGGTTTAAGATATTCCCCAAGGAGAG





TTCCTGGCCCGACCACAACACTAATGGCGTCACCGCCGCCTG





CTCACACGAGGGTAAGAACTCTTTTTACCGCAATCTGCTTTGG





CTTACTAAGAAGGAAAGCAGTTACCCGAATCTGGAGAACAGT





TACGTCAACAAGAAACGGAAAGAGGTCCTGGTGCTGTGGGG





AATTCACCACCCTTCCAATTCGAAGGAACAGCAGAATCTGTA





CCAAAACGAAAATGCTTACGTGAGTGTGGTGACCTCGAACTA





TAATAGACGATTCACACCTGAGATTGCCGAGCGTCCCAAAGT





TAAGGGCCAAGCCGGTAGGATGAACTACTACTGGACTCTCCT





GAAGCCCGGTGACACCATTATCTTCGAGGCCAATGGTAATCT





GATCGCCCCTATGTACGCTTTCGCACTGTCACGCGGGTTCGGA





TCTGGGATAATTACTTCGAACGCTAGCATGCATGAGTGTAAT





ACCAAGTGCCAGACCCCACTTGGAGCAATCAATTCCAGCCTA





CCTTATCAGAATATTCATCCCGTGACCATCGGAGAATGCCCA





AAGTACGTTAGGTCCGCTAAACTGAGGATGGTGACTGGCTTG





AGGAACATACCATCTATCCAATCTAGGGGCCTGTTTGGCGCT





ATTGCCGGGTTCATCGAGGGTGGCTGGACAGGCATGATTGAC





GGGTGGTACGGTTACCACCACCAGAACGAGCAGGGATCCGG





CTATGCAGCTGACCAGAAGTCAACCCAGAACGCAATCAACGG





CATCACAAATAAGGTCAATACTGTGATCGAAAAGATGAACAT





CCAATTCACTGCCGTGGGCAAGGAGTTTAATAAGCTCGAGAA





GCGCATGGAAAATCTGAACAAAAAAGTGGACGATGGCTTCCT





GGATATATGGACTTACAACGCCGAGCTCCTTGTGCTTCTGGA





GAACGAACGTACCTTGGACTTTCATGATAGTAACGTCAAGAA





TTTGTACGAGAAGGTTAAATCCCAGCTGAAGAACAATGCCAA





GGAAATCGGCAACGGCTGTTTTGAATTTTACCATAAATGCGA





CAATGAGTGCATGGAATCCGTACGCAATGGGACATACGATTA





CCCTAAATACTCCGAGGAAAGCAAGCTCAACCGAGAAAAAG





TGGACGGCGTCAAGCTCGAATCAATGGGTATTGGCAGTGCCG





GATCCGCCGGGTATATCCCCGAGGCCCCTAGAGACGGCCAAG





CCTATGTGCGGAAAGACGGCGAATGGGTTCTGCTATCCACCT





TCTTA









It should be understood that the 5′ and/or 3′ UTR for each construct may be omitted, modified or substituted for a different UTR sequences in any one of the vaccines as provided herein.


EQUIVALENTS

Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the disclosure described herein. Such equivalents are intended to be encompassed by the following claims.


All references, including patent documents, disclosed herein are incorporated by reference in their entirety.

Claims
  • 1-20. (canceled)
  • 21. An influenza virus vaccine, comprising: at least one ribonucleic acid polynucleotide having an open reading frame encoding at least one influenza virus antigenic polypeptide or an immunogenic fragment thereof, formulated in a lipid nanoparticle, wherein(i) the at least one RNA polypeptide is encoded by a nucleic acid sequence identified by any one of SEQ ID NO: 505-523 or 570-573, and/or(ii) the at least one RNA polypeptide comprises a nucleic acid sequence identified by any one of SEQ ID NO: 524-542 or 566-569, and/or(iii) the at least one antigenic polypeptide comprises an amino acid sequence identified by any one of SEQ ID NO: 543-565.
  • 22. The vaccine of claim 21, wherein the vaccine is multivalent.
  • 23. (canceled)
  • 24. A multiple consensus subtype vaccine comprising at least one messenger ribonucleic acid (mRNA) polynucleotide having an open reading frame encoding at least one influenza virus antigenic polypeptide, the influenza virus antigenic polypeptide selected from a nucleoprotein (NP), a neuraminidase (NA) protein, a matrix protein 1 (M1), a matrix protein 2 (M2), a nonstructural 1 (NS1) protein, and nonstructural 2 (NS2) protein, wherein the vaccine provides cross-reactivity against a variety of influenza strains, formulated in a lipid nanoparticle-comprising compounds of Formula (I):
  • 25. The vaccine of claim 24, wherein a subset of compounds of Formula (I) includes those in which when R4 is —(CH2)nQ, —(CH2)nCHQR, —CHQR, or —CQ(R)2, then (i) Q is not —N(R)2 when n is 1, 2, 3, 4 or 5, or (ii) Q is not 5, 6, or 7-membered heterocycloalkyl when n is 1 or 2.
  • 26. The vaccine of claim 24, wherein a subset of compounds of Formula (I) includes those in which R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′R′;R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;R4 is selected from the group consisting of a C3-6 carbocycle, —(CH2)nQ, —(CH2)nCHQR, —CHQR,-CQ(R)2, and unsubstituted C1-6 alkyl, where Q is selected from a C3-6 carbocycle, a 5- to 14-membered heteroaryl having one or more heteroatoms selected from N, O, and S, —OR, —O(CH2)nN(R)2, —C(O)OR, —OC(O)R, —CX3, —CX2H, —CXH2, —CN, —C(O)N(R)2, —N(R)C(O)R, —N(R)S(O)2R, —N(R)C(O)N(R)2, —N(R)C(S)N(R)2, —CRN(R)2C(O)OR, —N(R)R8, —O(CH2)nOR, —N(R)C(═NR9)N(R)2, —N(R)C(═CHR9)N(R)2, —OC(O)N(R)2, —N(R)C(O)OR, —N(OR)C(O)R, —N(OR)S(O)2R, —N(OR)C(O)OR, —N(OR)C(O)N(R)2, —N(OR)C(S)N(R)2, —N(OR)C(═NR9)N(R)2, —N(OR)C(═CHR9)N(R)2, —C(═NR9)N(R)2, —C(═NR9)R, —C(O)N(R)OR, and a 5- to 14-membered heterocycloalkyl having one or more heteroatoms selected from N, O, and S which is substituted with one or more substituents selected from oxo (═O), OH, amino, mono- or di-alkylamino, and C1-3 alkyl, and each n is independently selected from 1, 2, 3, 4, and 5;each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′)C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O)(OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;R8 is selected from the group consisting of C3-6 carbocycle and heterocycle;R9 is selected from the group consisting of H, CN, NO2, C1-6 alkyl, —OR, —S(O)2R, —S(O)2N(R)2, C2-6 alkenyl, C3-6 carbocycle and heterocycle;each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;each Y is independently a C3-6 carbocycle;each X is independently selected from the group consisting of F, Cl, Br, and I; andm is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,or salts or isomers thereof.
  • 27. The vaccine of claim 24, wherein a subset of compounds of Formula (I) includes those in which R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′R′;R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;R4 is selected from the group consisting of a C3-6 carbocycle, —(CH2)nQ, —(CH2)nCHQR, —CHQR,-CQ(R)2, and unsubstituted C1-6 alkyl, where Q is selected from a C3-6 carbocycle, a 5- to 14-membered heterocycle having one or more heteroatoms selected from N, O, and S, —OR, —O(CH2)nN(R)2, —C(O)OR, —OC(O)R, —CX3, —CX2H, —CXH2, —CN, —C(O)N(R)2, —N(R)C(O)R, —N(R)S(O)2R, —N(R)C(O)N(R)2, —N(R)C(S)N(R)2, —CRN(R)2C(O)OR, —N(R)R8, —O(C H2)nOR, —N(R)C(═NR9)N(R)2, —N(R)C(═CHR9)N(R)2, —OC(O)N(R)2, —N(R)C(O)OR, —N(OR)C(O)R, —N(OR)S(O)2R, —N(OR)C(O)OR, —N(OR)C(O)N(R)2, —N(OR)C(S)N(R)2, —N(OR)C(═NR9)N(R)2, —N(OR)C(═CHR9)N(R)2, —C(═NR9)R, —C(O)N(R)OR, and —C(═NR9)N(R)2, and each n is independently selected from 1, 2, 3, 4, and 5; and when Q is a 5- to 14-membered heterocycle and (i) R4 is —(CH2)nQ in which n is 1 or 2, or (ii) R4 is —(CH2)nCHQR in which n is 1, or (iii) R4 is-CHQR, and -CQ(R)2, then Q is either a 5- to 14-membered heteroaryl or 8- to 14-membered heterocycloalkyl;each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′)C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O)(OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;R8 is selected from the group consisting of C3-6 carbocycle and heterocycle;R9 is selected from the group consisting of H, CN, NO2, C1-6 alkyl, —OR, —S(O)2R, —S(O)2N(R)2, C2-6 alkenyl, C3-6 carbocycle and heterocycle;each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;each Y is independently a C3-6 carbocycle;each X is independently selected from the group consisting of F, Cl, Br, and I; andm is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,or salts or isomers thereof.
  • 28. The vaccine of claim 24, wherein a subset of compounds of Formula (I) includes those in which R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′R′;R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;R4 is selected from the group consisting of a C3-6 carbocycle, —(CH2)nQ, —(CH2)nCHQR, —CHQR,-CQ(R)2, and unsubstituted C1-6 alkyl, where Q is selected from a C3-6 carbocycle, a 5- to 14-membered heteroaryl having one or more heteroatoms selected from N, O, and S, —OR, —O(CH2)nN(R)2, —C(O)OR, —OC(O)R, —CX3, —CX2H, —CXH2, —CN, —C(O)N(R)2, —N(R)C(O)R, —N(R)S(O)2R, —N(R)C(O)N(R)2, —N(R)C(S)N(R)2, —CRN(R)2C(O)OR, —N(R)R8, —O(C H2)nOR, —N(R)C(═NR9)N(R)2, —N(R)C(═CHR9)N(R)2, —OC(O)N(R)2, —N(R)C(O)OR, —N(OR)C(O)R, —N(OR)S(O)2R, —N(OR)C(O)OR, —N(OR)C(O)N(R)2, —N(OR)C(S)N(R)2, —N(OR)C(═NR9)N(R)2, —N(OR)C(═CHR9)N(R)2, —C(═NR9)R, —C(O)N(R)OR, and —C(═NR9)N(R)2, and each n is independently selected from 1, 2, 3, 4, and 5;each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′)C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O)(OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;R8 is selected from the group consisting of C3-6 carbocycle and heterocycle;R9 is selected from the group consisting of H, CN, NO2, C1-6 alkyl, —OR, —S(O)2R, —S(O)2N(R)2, C2-6 alkenyl, C3-6 carbocycle and heterocycle;each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;each Y is independently a C3-6 carbocycle;each X is independently selected from the group consisting of F, Cl, Br, and I; andm is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,or salts or isomers thereof.
  • 29. The vaccine of claim 24, wherein subset of compounds of Formula (I) includes those in which R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′R′;R2 and R3 are independently selected from the group consisting of H, C2-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;R4 is —(CH2)nQ or —(CH2)·CHQR, where Q is —N(R)2, and n is selected from 3, 4, and 5;each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′)C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O)(OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;each R* is independently selected from the group consisting of C1-12 alkyl and C1-12 alkenyl;each Y is independently a C3-6 carbocycle;each X is independently selected from the group consisting of F, Cl, Br, and I; andm is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,or salts or isomers thereof.
  • 30. The vaccine of claim 24, wherein a subset of compounds of Formula (I) includes those in which R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′R′;R2 and R3 are independently selected from the group consisting of C1-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;R4 is selected from the group consisting of —(CH2)nQ, —(CH2)nCHQR, —CHQR, and -CQ(R)2, where Q is —N(R)2, and n is selected from 1, 2, 3, 4, and 5;each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′)C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O)(OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;each R* is independently selected from the group consisting of C1-12 alkyl and C1-12 alkenyl;each Y is independently a C3-6 carbocycle;each X is independently selected from the group consisting of F, Cl, Br, and I; andm is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,or salts or isomers thereof.
  • 31. The vaccine of claim 24, wherein a subset of compounds of Formula (I) includes those of Formula (IA):
  • 32. The vaccine of claim 24, wherein the consensus hemagglutinin antigen is selected from the group consisting of influenza hemagglutinin 1 (HA1) and/or hemagglutinin 2 (HA2).
  • 33. The vaccine of claim 24, wherein the vaccine comprises at least two mRNA, each encoding at least one influenza virus antigenic polypeptide and wherein at least one influenza virus antigenic polypeptide is HA1, HA2, or a combination of HA1 and HA2, and at least one influenza virus antigenic polypeptide is selected from the group consisting of neuraminidase (NA), nucleoprotein (NP), matrix protein 1 (M1), matrix protein 2 (M2), non-structural protein 1 (NS1) and non-structural protein 2 (NS2).
  • 34. The vaccine of claim 33, wherein at least one influenza virus antigenic polypeptide is HA1 and at least one influenza virus antigenic polypeptide is selected from the group consisting of NA, NP, M1, M2, NS1 and NS2.
  • 35. The vaccine of claim 34, wherein at least one influenza virus antigenic polypeptide is HA2 and at least one antigenic polypeptides is selected from the group consisting of NA, NP, M1, M2, NS1 and NS2.
  • 36. The vaccine of claim 33, wherein the at least one influenza virus antigenic polypeptide is from influenza virus strain H1/PuertoRico/8/1934, H1/New Caledonia/20/1999, H1/California/04/2009, H5/Vietnam/1194/2004, H2/Japan/305/1957, H9/Hong Kong/1073/99, H3/Aichi/2/1968, H3/Brisbane/10/2007, H7/Anhui/1/2013, H10/Jiangxi-Donghu/346/2013, H3/Wisconsin/67/2005, H1/Vietnam/850/2009, or a combination thereof.
  • 37. (canceled)
  • 38. The vaccine of claim 24, wherein the lipid nanoparticle further comprises a PEG-modified lipid, a sterol, and a non-cationic lipid.
  • 39. The vaccine of claim 38, wherein the lipid nanoparticle comprises a molar ratio of about 20-60% cationic lipid, 0.5-15% PEG-modified lipid, 25-55% sterol, and 5-25% non-cationic lipid.
  • 40. The vaccine of claim 39, wherein the non-cationic lipid is a neutral lipid and the sterol is a cholesterol.
  • 41. The vaccine of claim 24, wherein the nanoparticle has a polydispersity value of less than 0.4.
  • 42. The vaccine of claim 24, wherein the nanoparticle has a net neutral charge at a neutral pH value.
  • 43. The vaccine of claim 24, wherein the at least one RNA polynucleotide comprises at least one chemical modification.
  • 44. The vaccine of claim 43, wherein the chemical modification is selected from pseudouridine, N1-methylpseudouridine, N1-ethylpseudouridine, 2-thiouridine, 4′-thiouridine, 5-methylcytosine, 5-methyluridine, 2-thio-1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine, 2-thio-dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine, 4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine, 4-thio-pseudouridine, 5-aza-uridine, dihydropseudouridine, 5-methoxyuridine and 2′-O-methyl uridine.
  • 45. A method of inducing an immune response in a subject, the method comprising administering to the subject the vaccine of claim 24 in an amount effective to produce an antigen-specific immune response in the subject.
  • 46. The method of claim 45, wherein the antigen specific immune response comprises a T cell response or a B cell response.
  • 47-69. (canceled)
  • 70. A method of inducing cross-reactivity against a variety of influenza strains in a mammal, the method comprising administering to the mammal in need thereof the vaccine of claim 24.
  • 71. The method of claim 70, wherein at least two ribonucleic acid (RNA) polynucleotides having an open reading frame each encoding a consensus hemagglutinin antigen are administered to the mammal separately.
  • 72. The method of claim 70, wherein at least two ribonucleic acid (RNA) polynucleotides having an open reading frame each encoding a consensus hemagglutinin antigen are administered to the mammal simultaneously.
  • 73-75. (canceled)
RELATED APPLICATIONS

This application is a national stage filing under 35 U.S.C. § 371 of international application number PCT/US2018/022605, filed Mar. 15, 2018, which was published under PCT Article 21(2) in English and claims the benefit under 35 U.S.C. § 119(e) of U.S. provisional application No. 62/471,771, filed Mar. 15, 2017, and U.S. provisional application No. 62/490,057, filed Apr. 26, 2017, each of which is incorporated by reference herein in its entirety.

Provisional Applications (2)
Number Date Country
62471771 Mar 2017 US
62490057 Apr 2017 US
Continuations (1)
Number Date Country
Parent 16493986 Sep 2019 US
Child 18055193 US