PIV5-BASED CORONAVIRUS VACCINES AND METHODS OF USE THEREOF

Information

  • Patent Application
  • 20230105376
  • Publication Number
    20230105376
  • Date Filed
    September 20, 2022
    2 years ago
  • Date Published
    April 06, 2023
    a year ago
Abstract
The present invention provides constructs of the parainfluenza virus type-5 (PIV5) virus expressing the SARS-CoV-2 envelope spike (S) and nucleocapsid (N) proteins of SARS-CoV-2 variants for use as safe, stable, efficacious, and cost-effective vaccines against COVID-19.
Description
REFERENCE TO SEQUENCE LISTING

The instant application contains a Sequence Listing which has been submitted electronically in ST26 .XML format and is hereby incorporated by reference in its entirety. Said ST26 .XML copy, created on Sep. 20, 2022, is named “065095002US” and is 473 kilobytes in size.


FIELD OF THE INVENTION

The invention is generally related to the field of immunomodulation, and more particularly to compositions and methods for modulating immune responses in a subject.


BACKGROUND OF THE INVENTION

SARS-CoV-2 is a novel coronavirus that was first identified in Wuhan, China in December 2019 as a cause of pneumonia and has subsequently spread globally to cause the COVID-19 pandemic. According to the World Health Organization (WHO), since 2019, COVID-19 has spread globally, infected more than 519 million people, and caused at least 6 million deaths. SARS-CoV-2 initially infects the upper respiratory tract epithelium (Wolfel, R., et al., Nature, 581(7809):465 (2020)) but can progress to the lower respiratory tract to cause pneumonia and acute respiratory distress syndrome (ARDS) (Huang, C., et al., Lancet, 395(10223):497 (2020)). Since the beginning of the 2019 coronavirus disease (COVID-19) pandemic, numerous SARS-CoV-2 variants have emerged. WHO defines a SARS-CoV-2 variant of concern (VOC) as a variant that affects virus transmissibility and COVID-19 epidemiology, increases virulence and pathogenicity, or decreases the effectiveness of in-place public health measures. Current VOCs include delta and omicron, while previously circulating VOCs include alpha, beta, and gamma.


The global spread of SARS-CoV-2 prompted rapid development of prophylactic vaccines. Vaccines and antibody therapies have been introduced worldwide providing a ray of hope for the end of the COVID-19 pandemic. Currently, three vaccines are approved for use in the United States. The vaccines developed by Pfizer and Moderna are based on mRNA technology, while the vaccine produced by Johnson & Johnson (J&J) utilizes a human adenovirus type 26 vector. A vaccine produced by AstraZeneca employs a Chimpanzee adenovirus vector and is approved for use in the European Union (Ura, T., et al., Vaccine, 39(2): 197 (2021)). Since May 2022, 11 billion vaccine doses have been administered worldwide. However, SARS-CoV-2 variants have demonstrated immune escape in previously infected and fully vaccinated individuals. Compared to neutralization of alpha variant, serum from convalescent individuals was four-fold less effective against delta variant. The same study found that serum from individuals who received two doses of Pfizer's vaccine has delta-neutralizing abilities three- to five-fold lower than its alpha-neutralizing abilities. This immune escape was correlated to epitopes found on the SARS-CoV-2 spike protein (Planas, D., et al., Nature, 596(7871): 276 (2021)). Another study found that the omicron-neutralizing ability of serum from WA1-convalescent individuals is eight-fold lower than its WA1-neutralizing ability (Zhang, L., et al., Emerg Microbes Infect, 11(1): 1 (2022)). Analysis of published reports indicates that for individuals vaccinated with Pfizer, Moderna, J&J, or AstraZeneca vaccines, vaccine efficacy decreased by approximately 21 percentage points within one to six months after full vaccination. This decrease in efficacy was associated with waning immunity (Feikin, D. R., et al., Lancet, 399(10328): 924 (2022)).


Therefore, compounding waning immunity with the emergence of variants capable of immune escape, there is an urgent need for novel SARS-CoV-2 vaccine candidates with long-lasting immunity and protective against variants.


SUMMARY OF THE INVENTION

The present disclosure presents an intranasal viral-vectored vaccine against SARS-CoV-2 variants. The disclosure includes a viral expression vector having a parainfluenza virus 5 (PIV5) genome having a heterologous nucleic acid sequence with at least 98% sequence identity to SEQ ID NOs: 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, or 80, wherein the viral expression vector expresses a heterologous polypeptide comprising a coronavirus spike (S) and/or nucleocapsid (N) proteins.


In some aspects of the viral expression vector, the coronavirus S protein includes the coronavirus S protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the coronavirus N protein is the coronavirus N protein of SARS-CoV-2, a variant of interest or a variant of concern of SARS-CoV-2.


In some aspects of the viral expression vector, the coronavirus S protein is the coronavirus S protein of a SARS-CoV-2 beta variant, a SARS-CoV-2 gamma variant, a SARS-CoV-2 delta variant, or a SARS-CoV-2 omicron variant and the coronavirus N protein is the coronavirus N protein of a SARS-CoV-2 beta variant, a SARS-CoV-2 gamma variant, a SARS-CoV-2 delta variant, or a SARS-CoV-2 omicron variant.


In some aspects of the viral expression vector, the coronavirus S protein comprises the coronavirus S protein of SARS-CoV-2 and wherein the cytoplasmic tail of the coronavirus S protein has been replaced with the cytoplasmic tail of the fusion (F) protein of PINS.


In some aspects of the viral expression vector, the coronavirus S protein of a variant of SARS-CoV-2 has been inserted between the PIV5 small hydrophobic (SH) and hemagglutinin (HN) genes and the coronavirus N protein of a variant of SARS-CoV-2 has been inserted between the PIV5 HN and polymerase (L) genes.


In some aspects of the viral expression vector, the coronavirus S protein of a variant of SARS-CoV-2 has been inserted between the PIV5 HN and polymerase (L) genes.


In some aspects of the viral expression vector, the coronavirus S protein is a S protein from a variant of interest or a variant of concern of SARS-CoV-2 and the coronavirus N protein is a N protein from different variant of interest or a variant of concern of SARS-CoV-2.


In some aspects of the viral expression vector, the PIV5 small hydrophobic (SH) gene has been replaced with the coronavirus N protein of SARS-CoV-2.


In some aspects of the viral expression vector, the PIV5 genome further comprises one or more mutations comprising a mutation of the V/P gene, a mutation of the shared N-terminus of the V and P proteins, a mutation of residues 26, 32, 33, 50, 102, and/or 157 of the shared N-terminus of the V and P proteins, a mutation lacking the C-terminus of the V protein, a mutation lacking the small hydrophobic (SH) protein, a mutation of the fusion (F) protein, a mutation of the phosphoprotein (P), a mutation of the large RNA polymerase (L) protein, a mutation incorporating residues from canine parainfluenza virus, a mutation inducing apoptosis, or a combination thereof.


In some aspects of the viral expression vector, one or more mutations comprise PIV5VΔC, PIV5ΔSH, PIV5-P-S308G, or a combination thereof.


In some aspects of the viral expression vector, the heterologous polypeptide comprises a CPI V/P gene that contains mutations at amino acid residue S157 or S308, or the combination thereof, wherein serine (S) is substituted with an amino acid residue selected from a group consisting of alanine (A), asparagine (B), cysteine (C), aspartic acid (D), glutamic acid (E), phenylalanine (F), glycine (G), histidine (H), isoleucine (I), lysine (K), leucine (L), methionine (M), asparagine (N), proline (P), glutamine (Q), arginine (R), selenocysteine (U), valine (V), tryptophan (W), tyrosine (Y), and glutamine (Z).


In some aspects of the viral expression vector, the amino acid substitution at amino acid residue S157 comprises a substitution of serine (S) to phenylalanine (F) and the amino acid substitution at amino acid residue S308 comprises a substitution of serine (S) to alanine (A) or Glycine (G).


In some aspects of the viral expression vector, a viral particle comprises the viral expression vector.


The present disclosure also presents a composition comprising the viral expression vector presented above, a viral particle presented above, or a combination thereof.


In some aspects of the composition, a heterologous coronavirus spike (S) and nucleocapsid (N) proteins are expressed in a cell by contacting the cell with the composition.


The present disclosure also presents a method of inducing an immune response in a subject having coronavirus disease 2019 (COVID-19) to coronavirus spike (S) and nucleocapsid (N) proteins, the method comprising administering the composition presented above to the subject, wherein the immune response comprises a humoral immune response and/or a cellular immune response.


In some aspects of the method, the subject is vaccinated against COVID-19), the method comprising administering the composition to the subject.


In some aspects of the method, the composition is administered intranasally, intramuscularly, topically, or orally.


The present disclosure also presents a method of inducing in a subject an immune response comprising administering a PIV-5 booster vaccine composition comprising a viral expression vector or a viral particle having a PIV5 genome comprising a heterologous nucleic acid sequence with at least 98% sequence identity to SEQ ID NOs: 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, or 80, wherein said subject has previously received a primary vaccination against SARS-COV-2.





BRIEF DESCRIPTION OF THE DRAWINGS


FIG. 1 shows a schematic of the vaccine virus indicating the location of SARS-CoV-2 genes and their corresponding variant of origin.



FIG. 2 shows an outline of hamster immunization and challenge.



FIGS. 3A-3B show hamster study 1. Following challenge with SARS-CoV-2 WA1 (FIG. 3A) or CA1/alpha (FIG. 3B), the hamster weights were monitored. Weights are graphed as percent of weight on the day of immunization, or 0 dpi.



FIGS. 4A-4B show infectious SARS-CoV-2 in hamster lungs post-WA1 (FIG. 4A) or CA1/alpha (FIG. 4B) challenge. 5 dpc, lungs were harvested and lung homogenate was plagued on Vero cells. The limit of detection (LOD) is indicated by the dotted line.



FIGS. 5A-5D show SARS-CoV-2 RNA in hamster lungs post-WA1 (FIGS. 5A-5B) or CA1/alpha (FIGS. 5C-5D) challenge. CT values for each sample are plotted. The standard curves for challenge variant were used to calculate the CT value indicative of PCR-negative and 1 PFU/reaction (rxn).



FIG. 6 is a schematic of the study showing the efficacy of CVXGA1 and CVXGA3 in African green monkeys.



FIGS. 7A-7B show SARS-CoV-2 S-specific cellular immune response in immunized African green monkeys (AGMs). Prior vaccine dosing at day −1, and 7, 14, and 28 dpi, PBMCs were isolated from immunized AGMs. The PBMCs were stimulated with SARS-CoV-2 S peptide, and the number of IFN-γ spots were quantified. Graphed are the number of spots per 200,000 PBMCs.



FIG. 8 shows Anti-SARS-CoV-2 S IgG antibody response in immunized AGMs. Prior dosing at day −1 and 28 dpi, serum was collected from immunized AGMs, serially diluted and incubated on T96 plates coated with 1 μg/mL purified SARS-CoV-2 S protein. The wells were washed and incubated with anti-monkey IgG antibody conjugated to HRP. The wells were washed and incubated with KPL SureBlue RMB substrate. The antibody titer was calculated as log 10 of the highest serum dilution at which the OD450 was greater than two standard deviations above the mean OD450 of naïve serum. The dotted line indicates the limit of detection (LOD).



FIGS. 9A-9B show infectious SARS-CoV-2 challenge virus titer in nasal wash (FIG. 9A) and BAL (FIG. 9B). NW and BAL were collected at 2, 4, and 7 dpc. The samples were serially diluted and incubated on Vero cells. 1 hr post-infection, a methylcellulose overlay was added onto the cells. Three days post-infection, the cells were fixed and stained, and the plaques were counted.



FIGS. 10A-10B shows SARS-CoV-2 challenge virus RNA load in nasal wash (FIG. 10A) and BAL (FIG. 10B) qRT-PCR. 2, 4, and 7 dpc, NW and BAL were collected. The samples were mixed 1:10 in Trizol, and RNA was extracted. qRT-PCR was performed on the RNA samples. To calculate the PCR negative and theoretical 1 PFU/rxn values, a standard curve was generated with RNA extracted from SARS-CoV-2 alpha virus.



FIG. 11 is a schematic of the PIV5 and CVXGA vaccines. The PIV5 genome has 7 genes 3′ to 5′: NP, V/P, M, F, SH, HN, L. The S genes from SARS-CoV-2 WA1 (CVXGA1), beta variant (CVXGA3), gamma variant (CVXGA5), delta variant (CVXGA13), and omicron variant (CVXGA14) had their cytoplasmic tails replaced with the PIV5 F cytoplasmic tail and inserted between PIV5 genes SH and HN. CVXGA2 also has SARS-CoV-2 WA1 N between PIV5 HN and L genes.



FIGS. 12A-12AA show CVXGA vaccine antigen expression panels. Vero cells were infected at MOI 0.01 and fixed with 80% methanol at 3 days post-infection. FIGS. 12A-12S show intracellular expression of PIV5-V/P, SARS-CoV-2-S, and SARS-CoV-2-N. The cells were incubated with anti-PIV5 V/P, -SARS-CoV-2 S, or SARS-CoV-2 N antibodies, followed by Cy3-conjugated secondary antibody. The cells were washed with PBS and imaged at 10× with an EVOS M5000 microscope (Thermo Fisher Scientific). FIGS. 12T-12AA show cell-to-cell fusion induced by SARS-CoV-2 S expression. Infected cells were imaged at 10× with an Evos M5000 microscope. Arrows indicate syncytium, multinucleated cells.



FIGS. 13A-13B show that immunization of hamsters with CVXGA1, CVXGA2, CVXGA3, and CVXGA5 induces anti-SARS-CoV-2 S IgG antibodies. FIG. 13A shows intracellular expression of PIV5-V/P, SARS-CoV-2-S, and SARS-CoV-2-N. The cells were incubated with anti-PIV5 V/P, -SARS-CoV-2 S, or SARS-CoV-2 N antibodies, followed by Cy3-conjugated secondary antibody. The cells were washed with PBS and imaged at 10× with an EVOS M5000 microscope (Thermo Fisher Scientific). FIG. 13B shows cell-to-cell fusion induced by SARS-CoV-2 S expression. Infected cells were imaged at 10× with an Evos M5000 microscope. Arrows indicate syncytium, multinucleated cells.



FIGS. 14A-14F show immunization with CVXGA1 protects hamsters from challenge with SARS-CoV-2 WA1 and alpha variant. Following challenge with WA1 (FIG. 14A) or alpha variant (FIG. 14B), hamster weights were monitored daily for five days and graphed as percent day 0 weight. Statistical significance was calculated for each timepoint between each group and PIV5-immunized hamsters with t tests (* p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001). 5 dpc with WA1 (FIG. 14C) or alpha variant (FIG. 14D), the hamster lungs were harvested and homogenized in 1.7 mL PBS. Viral load was quantified via plaque assay in Vero E6 cells and graphed as PFU/mL lung homogenate. The limit of detection (LOD) is indicated by the dotted line. Error bars represent the standard error of the means. RNA was extracted from lung homogenate and SARS-CoV-2 WA1 (FIG. 14E) or alpha variant (FIG. 14F) vRNA was quantified via RT-qPCR. The cycle threshold (Ct) value for each sample is presented and error bars represent the standard error of the means. The known viral titers of WA1 and alpha variant were used to generate standard curves for FIG. 14E and FIG. 14F, respectively, and calculate the Ct values equating to 1 PFU per reaction (rxn). The Ct value generated from RNA extracted from sterile water is denoted by a dotted line labelled PCR negative. The limit of detection (LOD) is indicated by a dotted line at Ct value=40, the number of PCR cycles. Comparing each group to PIV5-immunized hamsters, statistical significance was calculated with one-way ANOVA (** p<0.01, *** p<0.001).



FIGS. 15A-15F show that immunization with CVXGA1 protects hamsters from challenge with SARS-CoV-2 delta variant. FIG. 15A is an immunization schematic. Golden Syrian hamsters (n=5) were intranasally immunized with 100 μL PBS, 3×105 PFU CVXGA1, 2×105 PFU CVXGA3, or 1.5×105 PFU CVXGA13. Blood was collected at 19 dpi. At 28 dpi, the hamsters were challenged with 104 PFU of SARS-CoV-2 delta variant. Following challenge infection, the hamster weights were monitored daily before terminating the study and harvesting lungs at 5 dpc. 19 dpc, anti-SARS-CoV-2 WA1 S (FIG. 15B) and RBD (FIG. 15C) IgG antibodies were quantified via ELISA. Antibody titer was calculated as log10 of the highest serum dilution at which the OD450 was greater than two standard deviations above the mean OD450 of naïve serum. The limit of detection (LOD) is indicated by the dotted line. Error bars represent the standard error of the means. Comparing each group to the vector control, statistical significance was calculated with one-way ANOVA (** p<0.01, **** p<0.0001). FIG. 15D shows the results following challenge. Hamster weights were monitored daily for five days and graphed as percent day 0 weight. Statistical significance was calculated for each timepoint between each group and PIV5-immunized hamsters with t tests (* p<0.05, ** p<0.01, *** p<0.001). 5 dpc, the hamster lungs were harvested and homogenized in 1.7 mL PBS. FIG. 15E shows viral load which was quantified via plaque assay in Vero TEMPRSS cells and graphed as PFU/mL lung homogenate. The limit of detection (LOD) is indicated by the dotted line. Error bars represent the standard error of the means. FIG. 15F shows RNA was extracted from lung homogenate and SARS-CoV-2 delta vRNA was quantified via RT-qPCR. The cycle threshold (Ct) value for each sample is presented and error bars represent the standard error of the means. The known viral titer of delta variant was used to generate a standard curves and calculate the Ct value equating to 1 PFU per reaction (rxn). The limit of detection (LOD), PCR negative, is indicated by a dotted line at Ct value=40, the number of PCR cycles.



FIGS. 16A-16H show that immunization with a Covid-19 mRNA vaccine, one dose of CVXGA1 or two doses of CVXGA1, protects hamsters against challenge with delta variant. FIG. 16A is a schematic of immunization. Golden Syrian hamsters received 100 μL PBS intranasally (n=5, Group 1), 2 μg mRNA COVID vaccine (n=25, Group 2), or 100 μL 7×104 PFU CVXGA1 (n=10, Groups 3 & 4). At 29 dpi, hamsters that received the mRNA vaccine were boosted with the mRNA vaccine again and group 3 hamsters received another dose of CVXGA1. At 91 dpi following initial immunization, hamsters who received two doses of mRNA received 2 μg mRNA vaccine (n=5, Group 2A), 100 μL 7×104 PFU CVXGA1 (n=5, Group 2B), 100 μL 103 PFU CVXGA13 (n=5, Group 2C), 100 μL PBS i.n. (n=5, Group 2D), or 100 μL 104 PFU CVXGA14 (n=5, Group 2E). Blood was collected at 36 and 108 dpi. At 116 dpi, the hamsters were challenged with 105 PFU SARS-CoV-2 delta variant. Following challenge infection, hamster weights were monitored for 5 days and the hamster lungs were harvested. FIG. 16B shows 36 and 108 days post-immunization, anti-SARS-CoV-2 WA1 S IgG antibodies were quantified via ELISA. Antibody titer was calculated as log10 of the highest serum dilution at which the OD450 was greater than two standard deviations above the mean OD450 of naïve serum. The limit of detection (LOD) is indicated by the dotted line. Error bars represent the standard error of the means. FIGS. 16C-16E show graphs of microneutralization assays performed. Hamster serum was heat-inactivated and serially diluted. The serum was mixed 1:1 with 6×103 focus-forming units (FFU)/mL SARS-CoV-2 WA1, delta, or omicron and incubated on Vero cells for WA1 or Vero TEMPRSS2 cells for delta and omicron. After 24 hr, the number of infected cells were quantified via immunostain. Neutralization titers were calculated as log10 of the highest serum dilution at which the virus infectivity was reduced by at least 50%. The limit of detection (LOD) is indicated by the dotted line. FIG. 16F shows that following challenge, hamster weights were monitored daily for five days and graphed as percent day 0 weight. Statistical significance was calculated for each timepoint between each group and PBS-immunized hamsters with t tests (* p≤0.05). 5 dpc, the hamster lungs were harvested and homogenized in 1.7 mL PBS. FIG. 16G shows a graph where viral load was quantified via plaque assay in Vero TEMPRSS cells and graphed as PFU/mL lung homogenate. The limit of detection (LOD) is indicated by the dotted line. Error bars represent the standard error of the means. FIG. 16H shows a graph where RNA was extracted from lung homogenate and SARS-CoV-2 delta vRNA was quantified via RT-qPCR. The cycle threshold (Ct) value for each sample is presented and error bars represent the standard error of the means. The known viral titer of delta variant was used to generate a standard curve and calculate the Ct value equating to 1 PFU per reaction (rxn). The Ct value generated from RNA extracted from sterile water is denoted by a dotted line labelled PCR negative. The limit of detection (LOD) is indicated by a dotted line at Ct value=40, the number of PCR cycles. Error bars represent the standard error of the means. Statistical significance was calculated with one-way ANOVA (** p<0.01, **** p<0.0001).



FIGS. 17A-17E are graphs showing that, following two doses of a Covid-19 mRNA vaccine, CVXGA1 boosts the humoral immune response and elicits protection of hamsters against challenge with delta variant. FIG. 17A is a graph showing, anti-SARS-CoV-2 S IgG antibodies 17 days post-boost which were quantified via ELISA. Antibody titer was calculated as log10 of the highest serum dilution at which the OD450 was greater than two standard deviations above the mean OD450 of naïve serum. The limit of detection (LOD) is indicated by the dotted line. Error bars represent the standard error of the means. Statistical significance was calculated with one-way ANOVA (**** p<0.0001). FIG. 17 B shows microneutralization assays were performed with post-boost sera. Hamster serum was heat-inactivated and serially diluted. The serum was mixed 1:1 with 6×103 focus-forming units (FFU)/mL SARS-CoV-2 WA1, delta, or omicron and incubated on Vero cells for WA1 or Vero TEMPRSS2 cells for delta and omicron. After 24 hr, the number of infected cells were quantified via immunostain. Neutralization titers were calculated as log10 of the highest serum dilution at which the virus infectivity was reduced by at least 50%. The limit of detection (LOD) is indicated by the dotted line. Statistical significance was calculated between each group and the PBS group with one-way ANOVA (* p≤0.05, ** p<0.01, *** p<0.001, **** p<0.0001). FIG. 17C is a line graph showing that, following challenge, hamster weights were monitored daily for five days and graphed as percent day 0 weight. Statistical significance was calculated for each timepoint between each group and PBS-immunized hamsters with t tests (* p≤0.05, ** p<0.01). 5 dpc, the hamster lungs were harvested and homogenized in 1.7 mL PBS. FIG. 17D shows that no detectable infectious virus in their lungs were observed in boosted hamsters. FIG. 17E shows viral load quantified via plaque assay in Vero TEMPRSS cells and graphed as PFU/mL of lung homogenate. The limit of detection (LOD) is indicated by the dotted line. Error bars represent the standard error of the means. FIG. 17F shows RNA was extracted from lung homogenate and SARS-CoV-2 delta vRNA was quantified via RT-qPCR. The cycle threshold (Ct) value for each sample is presented and error bars represent the standard error of the means. The known viral titer of delta variant was used to generate a standard curve and calculate the Ct value equating to 1 PFU per reaction (rxn). The Ct value generated from RNA extracted from sterile water is denoted by a dotted line labelled PCR negative. The limit of detection (LOD) is indicated by a dotted line at Ct value=40, the number of PCR cycles. Error bars represent the standard error of the means. Statistical significance was calculated with one-way ANOVA (** p<0.01, **** p<0.0001).



FIGS. 18A-18C show RT-qPCR standard curves. RNA was extracted from SARS-CoV-2 WA1 (FIG. 18A), alpha variant (FIG. 18B), and delta variant (FIG. 18C) viral stocks of known titer. The RNA was serially diluted and vRNA was quantified via RT-qPCR. To generate a standard curve, the Ct value was plotted on the y-axis and the PFU per reaction (rxn) was plotted on the x-axis. Dotted lines indicate the Ct value which corresponds to 1 PFU/rxn.



FIGS. 19A-19B are schematics of PIV5 CPI based SARS-CoV-2 vaccine constructs.





DETAILED DESCRIPTION OF THE INVENTION
A. Definitions

To facilitate an understanding of the principles and features of the various embodiments of the disclosure, various illustrative embodiments are explained herein. Although exemplary embodiments of the disclosure are explained in detail, it is to be understood that other embodiments are contemplated. Accordingly, it is not intended that the disclosure is limited in its scope to the details of construction and arrangement of components set forth in the description or examples. The disclosure is capable of other embodiments and of being practiced or carried out in various ways.


In describing the exemplary embodiments, specific terminology will be resorted to for the sake of clarity. As used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural references unless the context clearly dictates otherwise. For example, reference to a component is intended also to include composition of a plurality of components. References to a composition containing “a” constituent is intended to include other constituents in addition to the one named.


Ranges may be expressed herein as from “about” or “approximately” or “substantially” one particular value and/or to “about” or “approximately” or “substantially” another particular value. When such a range is expressed, other exemplary embodiments include from the one particular value and/or to the other particular value.


Similarly, as used herein, “substantially free” of something, or “substantially pure”, and like characterizations, can include both being “at least substantially free” of something, or “at least substantially pure”, and being “completely free” of something, or “completely pure.”


The terms “patient”, “individual”, “subject”, and “animal” are used interchangeably herein and refer to mammals, including, without limitation, human and veterinary animals (e.g., cats, dogs, cows, horses, sheep, pigs, etc.) and experimental animal models. In a preferred embodiment, the subject is a human.


As used herein, the term “combination” of a PIV5-based AVLP composition as described herein and at least a second pharmaceutically active ingredient means at least two, but any desired combination of compounds can be delivered simultaneously or sequentially (e.g., within a 24-hour period). It is contemplated that when used to treat various diseases, the compositions and methods of the present disclosure can be utilized with other therapeutic methods/agents suitable for the same or similar diseases. Such other therapeutic methods/agents can be co-administered (simultaneously or sequentially, in any order) to generate additive or synergistic effects. Suitable therapeutically effective dosages for each agent may be lowered due to the additive action or synergy. Also, two or more embodiments of the disclosure may be also co-administered to generate additive or synergistic effects.


The term “coronavirus” refers to a group of related RNA viruses that cause diseases in mammals and birds. In humans, these viruses cause respiratory tract infections that can range from mild to lethal. Mild illnesses include some cases of the common cold (which is caused also by certain other viruses, predominantly rhinoviruses), while more lethal varieties can cause SARS, MERS, and COVID-19. There are presently no vaccines or antiviral drugs to prevent or treat human coronavirus infections.


The term “SARS” or “severe acute respiratory syndrome” refers to a viral respiratory disease of zoonotic origin that surfaced in the early 2000s caused by severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1), the first-identified strain of the SARS coronavirus species severe acute respiratory syndrome-related coronavirus (SARS-CoV). The syndrome caused the 2002-2004 SARS outbreak. In 2019, its successor, the related virus strain Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was discovered.


The term “Covid-19” or “Coronavirus disease 2019” refers to a severe acute respiratory syndrome (SARS) caused by a virus known as SARS-Coronavirus 2 (SARS-CoV2).


As described herein, the term “vaccinating” designates typically the sequential administration of one or more antigens to a subject, to produce and/or enhance an immune response against the antigen(s). The sequential administration includes a priming immunization followed by one or several boosting immunizations.


Within the context of the present invention, the term “pathogen” refers to any agent that can cause a pathological condition. Examples of “pathogens” include, without limitation, cells (e.g., bacteria cells, diseased mammal cells, cancer mammal cells), fungus, parasites, viruses, prions or toxins. Preferred pathogens are infectious pathogens. In a particular embodiment, the infectious pathogen is a virus, such as the coronaviruses.


An antigen, as used therein, designates any molecule which can cause a T-cell or B-cell immune response in a subject. An antigen specific for a pathogen is, typically, an element obtained or derived from said pathogen, which contains an epitope, and which can cause an immune response against the pathogen. Depending on the pathogenic agent, the antigen may be of various nature, such as a (poly)peptide, protein, nucleic acid, lipid, cell, etc. Live weakened forms of pathogens (e.g., bacteria, viruses), or killed or inactivated forms thereof may be used as well, or purified material therefrom such as proteins, peptides, lipids, etc. The antigen may be naturally-occurring or artificially created. It may be exogenous to the treated mammal, or endogenous (e.g., tumor antigens). The antigen may be produced by techniques known per se in the art, such as for instance synthetic or recombinant technologies, or enzymatic approaches.


In a particular embodiment, the antigen is a protein, polypeptide and/or peptide. The terms “polypeptide”, “peptide” and “protein” are used interchangeably herein to refer to a polymer of amino acid residues. The terms also apply to amino acid polymers in which one or more amino acid residues may be modified or non-naturally occurring residues, such as an artificial chemical mimetic of a corresponding naturally occurring amino acid. It should be understood that the term “protein” also includes fragments or variants of different antigens, such as epitope-containing fragments, or proteins obtained from a pathogen and subsequently enzymatically, chemically, mechanically or thermally modified.


A “therapeutically effective amount” means the amount of a compound (e.g., a PIV5-based composition as described herein) that, when administered to a subject for treating a state, disorder or condition, is sufficient to effect such treatment. The “therapeutically effective amount” will vary depending on the compound or bacteria administered as well as the disease and its severity and the age, weight, physical condition and responsiveness of the mammal to be treated.


The phrase “pharmaceutically acceptable”, as used in connection with compositions of the disclosure, refers to molecular entities and other ingredients of such compositions that are physiologically tolerable and do not typically produce untoward reactions when administered to a mammal (e.g., a human). Preferably, as used herein, the term “pharmaceutically acceptable” means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in mammals, and more particularly in humans.


The term “pharmaceutically acceptable composition” as used herein refers to a composition comprising at least one compound as disclosed herein formulated together with one or more pharmaceutically acceptable carriers.


The term “administration” refers to the introduction of an amount of a predetermined substance into a patient by a certain suitable method. The composition disclosed herein may be administered via any of the common routes, as long as it is able to reach a desired tissue, for example, but is not limited to, inhaling, intraperitoneal, intravenous, intramuscular, subcutaneous, intradermal, oral, topical, intranasal, intrapulmonary, or intrarectal administration. However, since peptides are digested upon oral administration, active ingredients of a composition for oral administration should be coated or formulated for protection against degradation in the stomach.


The term “dose” means a single amount of a compound or an agent that is being administered thereto; and/or “regimen: which means a plurality of pre-determined doses that can be different in amounts or similar, given at various time intervals, which can be different or similar in terms of duration. In some embodiments, a regimen also encompasses a time of a delivery period (e.g., agent administration period, or treatment period). Alternatively, a regimen is a plurality of predetermined plurality pre-determined vaporized amounts given at pre-determined time intervals.


The term “carrier” refers to a diluent, adjuvant, excipient, or vehicle with which the compound is administered. Such pharmaceutical carriers can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like. Water or aqueous solution saline solutions and aqueous dextrose and glycerol solutions are preferably employed as carriers, particularly for injectable solutions. Alternatively, the carrier can be a solid dosage form carrier, including but not limited to one or more of a binder (for compressed pills), a glidant, an encapsulating agent, a flavorant, and a colorant. Suitable pharmaceutical carriers are described in “Remington's Pharmaceutical Sciences” by E. W. Martin.


The terms “treat” or “treatment” of a state, disorder or condition include: (1) preventing or delaying the appearance of at least one clinical or sub-clinical symptom of the state, disorder or condition developing in a subject that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition; or (2) inhibiting the state, disorder or condition, i.e., arresting, reducing or delaying the development of the disease or a relapse thereof (in case of maintenance treatment) or at least one clinical or sub-clinical symptom thereof; or (3) relieving the disease, i.e., causing regression of the state, disorder or condition or at least one of its clinical or sub-clinical symptoms. The benefit to a subject to be treated is either statistically significant or at least perceptible to the patient or to the physician.


As used herein, the term “parainfluenza virus 5” (PIV5) includes, for example and not limitation, strains KNU-11, CC-14, D277, 1168-1, and 08-1990. Non-limiting examples of PIV5 genomes are listed in GenBank Accession Nos. NC_006430.1, AF052755.1, KC852177.1, KP893891.1, KC237065.1, KC237064.1 and KC237063.1, which are hereby incorporated by reference.


By “comprising” or “containing” or “including” is meant that at least the named compound, element, particle, or method step is present in the composition or article or method, but does not exclude the presence of other compounds, materials, particles, method steps, even if the other such compounds, material, particles, method steps have the same function as what is named.


The mention of one or more method steps does not preclude the presence of additional method steps or intervening method steps between those steps expressly identified. Similarly, it is also to be understood that the mention of one or more components in a composition does not preclude the presence of additional components than those expressly identified.


The materials described as making up the various elements of the disclosure are intended to be illustrative and not restrictive. Many suitable materials that would perform the same or a similar function as the materials described herein are intended to be embraced within the scope of the disclosure. Such other materials not described herein can include, but are not limited to, for example, materials that are developed after the time of the development of the disclosure.


B. SARS-COV-2 Compositions

The disclosure provides PIV5-based compositions, systems and methods for their use in multiple applications including functional genomics, drug discovery, target validation, protein production (e.g., therapeutic proteins, vaccines, monoclonal antibodies), gene therapy, and therapeutic treatments such as cancer therapy.


I. SARS-CoV-2


With the present invention, constructs of the parainfluenza virus type-5 (PIV5) virus expressing the SARS-CoV-2 envelope spike (S) and nucleocapsid (N) protein have been generated for use as vaccines against COVID. These constructs demonstrate effectiveness as vaccines, with single dose intranasal immunization inducing sterilizing immunity in ferrets and cats.


Coronavirus disease 2019 (COVID-19) is a newly emerging infectious disease currently spreading across the world. It is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Zhu et al., 2020, N Engl J Med; 382:727-733). SARS-CoV-2 was first identified in Wuhan, China in December 2019, and has subsequently spread globally to cause the COVID-19 pandemic. The virus has infected more than 221 million persons world-wide, caused more than 4,574,000 deaths as of Sep. 8, 2021, and is poised to continue to spread in the absence of herd immunity. While vaccines and antibody therapies have been introduced worldwide, the emergence of multiple viral variants which are rapidly replacing the original virus identified in Wuhan has allowed for immune escape in vaccinated populations, presenting a need for improved vaccine efficacy.


SARS-CoV-2 is a single-stranded RNA-enveloped virus belonging to the B coronavirus family (Lu et al., 2020, Lancet; 395:565-74). An RNA-based metagenomic next-generation sequencing approach has been applied to characterize its entire genome, which is 29,881 nucleotides (nt) in length (GenBank Sequence Accession MN908947) encoding 9860 amino acids (Chen et al., 2020, Emerg Microbes Infect; 9:313-9). Full-genome sequenced genomes available at GenBank include isolate 2019-nCoV WHU01 (GenBank accession number MN988668) and NC_045512 for SARS-CoV-2, both isolates from Wuhan, China, and at least seven additional sequences (MN938384.1, MN975262.1, MN985325.1, MN988713.1, MN994467.1, MN994468.1, and MN997409.1) which are >99.9% identical and are hereby incorporate by reference.


1. SARS-CoV-2 Variants


Since SARS-CoV-2 was first identified in 2019, multiple genetic variants of SARS-CoV-2 have been emerging and circulating around the world. Viral mutations and variants in the United States are routinely monitored through sequence-based surveillance, laboratory studies, and epidemiological investigations. The US government SARS-CoV-2 Interagency Group (SIG) developed a Variant Classification scheme that defines three classes of SARS-CoV-2 variants: variant of interest, variant of concern and variant of high consequence.


a. Variant of Interest


A SARS-CoV-2 variant of interest is a variant with specific genetic markers that have been associated with changes to receptor binding, reduced neutralization by antibodies generated against previous infection or vaccination, reduced efficacy of treatments, potential diagnostic impact, or predicted increase in transmissibility or disease severity.


A variant of interest might require one or more appropriate public health actions, including enhanced sequence surveillance, enhanced laboratory characterization, or epidemiological investigations to assess how easily the virus spreads to others, the severity of disease, the efficacy of therapeutics and whether currently approved or authorized vaccines offer protection. The growing list variants of interest that are being monitored and characterized include, but are not limited to, Eta, Iota, Kappa, Lambda and Mu.


b. Variant of Concern


A SARS-CoV-2 variant of concern is a variant for which there is evidence of an increase in transmissibility, more severe disease (e.g., increased hospitalizations or deaths), significant reduction in neutralization by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures. Possible attributes of a variant of concern include evidence of impact on diagnostics, treatments, or vaccines, widespread interference with diagnostic test targets, evidence of substantially decreased susceptibility to one or more class of therapies, evidence of significant decreased neutralization by antibodies generated during previous infection or vaccination, evidence of reduced vaccine-induced protection from severe disease, evidence of increased transmissibility and evidence of increased disease severity.


Variants of concern might require one or more appropriate public health actions, such as notification to WHO under the International Health Regulations, reporting to CDC, local or regional efforts to control spread, increased testing, or research to determine the effectiveness of vaccines and treatments against the variant. Based on the characteristics of the variant, additional considerations may include the development of new diagnostics or the modification of vaccines or treatments. The growing list of variants of concern that are being closely monitored and characterized, includes, but is not limited to, Alpha, Beta, Delta, and Gamma.


c. Variant of High Consequence


A SARS-CoV-2 variant of high consequence has clear evidence that prevention measures or medical countermeasures (MCMs) have significantly reduced effectiveness relative to previously circulating variants. Possible attributes of a variant of high consequence include a demonstrated failure of diagnostic test targets, evidence to suggest a significant reduction in vaccine effectiveness, a disproportionately high number of vaccine breakthrough cases, or very low vaccine-induced protection against severe disease, significantly reduced susceptibility to multiple Emergency Use Authorization (EUA) or approved therapeutics and more severe clinical disease and increased hospitalizations.


A variant of high consequence would require notification to WHO under the International Health Regulations, reporting to CDC, an announcement of strategies to prevent or contain transmission, and recommendations to update treatments and vaccines. Currently, there are no SARS-CoV-2 variants that rise to the level of high consequence.


II. Parainfluenza Virus 5 (PIV5)


Parainfluenza virus 5 (PIV5), a negative-stranded RNA virus, is a member of the Rubulavirus genus of the family Paramyxoviridae which includes many important human and animal pathogens such as mumps virus, human parainfluenza virus type 2 and type 4, Newcastle disease virus, Sendai virus, HPIV3, measles virus, canine distemper virus, rinderpest virus and respiratory syncytial virus. PIV5 was previously known as Simian Virus-5 (SV5). Although PIV5 is a virus that infects many animals and humans, no known symptoms or diseases in humans have been associated with PIV5. Unlike most paramyxoviruses, PIV5 infect normal cells with little cytopathic effect. As a negative stranded RNA virus, the genome of PIV5 is very stable. As PIV5 does not have a DNA phase in its life cycle and it replicates solely in cytoplasm, PIV5 is unable to integrate into the host genome. Therefore, using PIV5 as a vector avoids possible unintended consequences from genetic modifications of host cell DNAs. PIV5 can grow to high titers in cells, including Vero cells which have been approved for vaccine production by WHO and FDA. Thus, PIV5 presents many advantages as a vaccine vector.


A PIV5-based vaccine vector of the present invention may be based on any of a variety of wild type, mutant, or recombinant (rPIV5) strains. Wild type strains include, but are not limited to, the PIV5 strains W3A, WR (ATCC® Number VR-288TM), canine parainfluenza virus strain 78-238 (ATCC number VR-1573) (Evermann et al., 1980, J Am Vet Med Assoc; 177:1132-1134; and Evermann et al., 1981, Arch Virol; 68:165-172), canine parainfluenza virus strain D008 (ATCC number VR-399) (Binn et al., 1967, Proc Soc Exp Biol Med; 126:140-145), MIL, DEN, LN, MEL, cryptovirus, CPI+, CPI−, H221, 78524, T1 and SER. See, for example, Chatziandreou et al., 2004, J Gen Virol; 85(Pt 10):3007-16; Choppin, 1964, Virology: 23:224-233; and Baumgartner et al., 1987, Intervirology; 27:218-223. Additionally, PIV5 strains used in commercial kennel cough vaccines, such as, for example, BI, FD, Merck, and Merial vaccines, may be used.


III. PIV5 CPI Vectored SARS-CoV-2 Constructs


A PIV5 vaccine vector of the present invention may be constructed using any of a variety of methods, including, but not limited to, the reverse genetics system described in more detail in He et al. (Virology; 237(2):249-60, 1997). PIV5 encodes eight viral proteins. Nucleocapsid protein (NP), phosphoprotein (P) and large RNA polymerase (L) protein are important for transcription and replication of the viral RNA genome. The V protein plays important roles in viral pathogenesis as well as viral RNA synthesis. The fusion (F) protein, a glycoprotein, mediates both cell-to-cell and virus-to-cell fusion in a pH-independent manner that is essential for virus entry into cells. The structures of the F protein have been determined and critical amino acid residues for efficient fusion have been identified. The hemagglutinin-neuraminidase (HN) glycoprotein is also involved in virus entry and release from the host cells. The matrix (M) protein plays an important role in virus assembly and budding. The hydrophobic (SH) protein is a 44-residue hydrophobic integral membrane protein and is oriented in membranes with its N terminus in the cytoplasm. For reviews of the molecular biology of paramyxoviruses see, for example, Whelan et al., 2004, Curr Top Microbiol Immunol; 283:61-119; and Lamb & Parks, (2006). Paramyxoviridae: the viruses and their replication. In Fields Virology, 5th edn, pp. 1449-1496. Edited by D. M. Knipe & P. M. Howley. Philadelphia, Pa.: Lippincott Williams & Wilkins.


Previously, recombinant PIV5 viruses expressing foreign genes from numerous pathogens, including Influenza, Rabies, Respiratory Syncytial Virus, Tuberculosis, Burkholderia, and MERS-CoV have been generated and tested as vaccine candidates (Li, Z., et al., J Virol, 87(1):354 (2013); Chen, Z., et al., J Virol, 87(6): 2986 (2013); Wang, D., et al., J Virol, 91(11) (2017); Chen, Z., et al., Vaccine, 33(51):7217 (2015); Lafontaine, E. R., et al., Vaccine X., 1:100002 (2018); Li, K., et al., mBio, 11(2) (2020)). Because it actively replicates in the respiratory tract following intranasal immunization, PIV5-vectored vaccines can generate mucosal immunity that includes antigen-specific IgA antibodies and long-lived IgA plasma cells (Wang, D., et al., J Virol, 91(11) (2017). Xiao, P., et al., Front Immunol., 12:623996 (2021)). Recently a PIV5-vectored vaccine expressing the spike protein from SARS-CoV-2 Wuhan (WA1; CVXGA1) has been shown to be efficacious in mice and ferrets. A single, intranasal dose of CVXGA1 induced WA1-neutralizing antibodies and protected K18-hACE2 mice against lethal infection with SARS-CoV-2 WA1. Furthermore, a single, intranasal dose of CVXGA1 protected ferrets from infection with SARS-CoV-2 WA1 and blocked transmission to cohoused naïve ferrets (An, D., et al., Sci Adv, 7(27) (2021)). While these studies determined its efficacy against SARS-CoV-2 WA1, further studies were necessary to establish its efficacy against SARS-CoV-2 variants.


1. PIV5-Based Vaccine Vectors Encoding the SARS-CoV-2 Spike (S) Protein


With the PIV5-based vaccine vectors of the present invention, a heterologous nucleotide sequence encoding the spike (S) protein of a coronavirus, including, but not limited to, the S protein of SARS-CoV-2, is inserted in the PIV5 genome. Coronavirus entry into host cells is mediated by the transmembrane S glycoprotein (Tortorici and Veesler, 2019, Adv Virus Res; 105:93-116). As the coronavirus S glycoprotein is surface-exposed and mediates entry into host cells, it is the main target of neutralizing antibodies upon infection and the focus of therapeutic and vaccine design. The spike S protein of SARS-CoV-2 is composed of two subunits, S1 and S2. The S1 subunit contains a receptor-binding domain that recognizes and binds to the host receptor angiotensin-converting enzyme 2, while the S2 subunit mediates viral cell membrane fusion by forming a six-helical bundle via the two-heptad repeat domain. (Huang et al., 2020, Acta Pharmacol Sinica; 0:1-9 (available on the worldwide web at doi.org/10.1038/s41401-020-0485-4).


The total length of SARS-CoV-2 S is 1273 amino acids (aa) and consists of a signal peptide (amino acids 1-13) located at the N-terminus, the S1 subunit (14-685 residues), and the S2 subunit (686-1273 residues); the last two regions are responsible for receptor binding and membrane fusion, respectively. In the S1 subunit, there is an N-terminal domain (14-305 residues) and a receptor-binding domain (RBD, 319-541 residues); the fusion peptide (FP) (788-806 residues), heptapeptide repeat sequence 1 (HR1) (912-984 residues), HR2 (1163-1213 residues), TM domain (1213-1237 residues), and cytoplasm domain (1237-1273 residues) comprise the S2 subunit (Xia et al., 2020, Cell Mol Immunol; 17:765-7).


In some PIV5-based vaccine vectors of the present invention, the heterologous nucleotide sequence encoding the spike (S) protein of a coronavirus, including, but not limited to, the S protein of SARS-CoV-2, has been modified so that the cytoplasmic tail of the coronavirus S protein has been replaced with the cytoplasmic tail of the fusion (F) protein of PIV5. An example of such a PIV5 construct includes the PIV5 construct CVX-GA1, also referred to herein as CVXGA1, CVX-UGA1, pDA27, or DA27. CVXGA1, recombinant PIV5 expressing S from SARS-CoV-2 WA1, is currently under phase 1 clinical trial in the US (ClinicalTrials.gov. Phase 1 Study of Intranasal PIV5-vectored COVID-19 Vaccine Expressing SARS-CoV-2 Spike Protein in Healthy Adults (CVXGA1-001) 2021).


In some PIV5-based vaccine vectors of the present invention, the heterologous nucleotide sequence encoding the coronavirus S protein, including but not limited to, the S protein of SARS-CoV-2, has been modified so that the S protein includes an amino acid substitution at amino acid residue W886 and/or F888. In some aspects, the amino acid substitution at amino acid residue W886 includes a substitution of tryptophan (W) to arginine (R) and/or the amino acid substitution at amino acid residue W888 includes a substitution of phenylalanine (F) to arginine (R).


In some PIV5-based vaccine vectors of the present invention, the heterologous nucleotide sequence encoding the spike (S) protein of a coronavirus, including, but not limited to, the S protein of SARS-CoV-2, includes both a modification so that the cytoplasmic tail of the coronavirus S protein has been replaced with the cytoplasmic tail of the fusion (F) protein of PIV5 and includes an amino acid substitution at amino acid residue W886 and/or F888. In some aspects, the amino acid substitution at amino acid residue W886 includes a substitution of tryptophan (W) to arginine (R) and/or the amino acid substitution at amino acid residue W888 includes a substitution of phenylalanine (F) to arginine (R). An example of such a PIV5 construct includes the PIV5 construct CVX-GA2, also referred to herein as CVXGA2 or CVX-UGA2.


The heterologous nucleotide sequence encoding the coronavirus S protein, including but not limited to the S protein of SARS-CoV-2, may be inserted in any of a variety of locations in the PIV5 genome.


In some embodiments, the heterologous nucleotide sequence encoding the coronavirus S protein, including but not limited to the S protein of SARS-CoV-2, may be inserted between the small hydrophobic protein (SH) gene and the hemagglutinin-neuraminidase (HN) gene of the PIV5 genome.


The heterologous nucleotide sequence encoding the coronavirus S protein, including but not limited to the S protein of SARS-CoV-2, may be inserted between the hemagglutinin-neuraminidase (HN) and large RNA polymerase protein (L) gene of the PIV5 genome. In some embodiments, the heterologous nucleotide sequence is not inserted at a location between the hemagglutinin-neuraminidase (HN) and large RNA polymerase protein (L) gene of the PIV5 genome. In some embodiments, the heterologous nucleotide sequence is inserted at a location other than between the hemagglutinin-neuraminidase (FIN) and large RNA polymerase protein (L) gene of the PIV5 genome.


The heterologous nucleotide sequence encoding the coronavirus S protein, including but not limited to the S protein of SARS-CoV-2, may be inserted between the nucleocapsid protein (NP) gene and the V/P gene of the PIV5 genome.


The heterologous nucleotide sequence encoding the coronavirus S protein, including but not limited to the S protein of SARS-CoV-2, may be inserted between the M gene and the F gene of the PIV5 genome.


The heterologous nucleotide sequence encoding the coronavirus S protein, including but not limited to the S protein of SARS-CoV-2, may be inserted between the F gene and the SH gene of the PIV5 genome.


The heterologous nucleotide sequence encoding the coronavirus S protein, including but not limited to the S protein of SARS-CoV-2, may be inserted between the VP gene and the matrix protein (M) gene of the PIV5 genome.


The heterologous nucleotide sequence encoding the coronavirus S protein, including but not limited to the S protein of SARS-CoV-2, may be inserted between the leader sequence and the nucleocapsid protein (NP) gene of the PIV5 genome.


The heterologous nucleotide sequence encoding the coronavirus S protein, including but not limited to the S protein of SARS-CoV-2, may be inserted immediately downstream of the leader sequence of the PIV5 genome.


The heterologous nucleotide sequence encoding the coronavirus S protein, including but not limited to the S protein of SARS-CoV-2, may be inserted to replace all or part of a PIV5 gene within the PIV5 genome. For example, the heterologous nucleotide sequence may replace the F, HN, or SH gene of the PIV5 genome. A heterologous nucleotide sequence may be inserted within a PIV5 gene, resulting in the expression of a chimeric polypeptide. For example, the heterologous nucleotide sequence may be inserted within the SH gene nucleotide sequence, within the NP gene nucleotide sequence, within the V/P gene nucleotide sequence, within the M gene nucleotide sequence, within the F gene nucleotide sequence, within the HN gene nucleotide sequence, and/or within the L gene nucleotide sequence of a PIV5 genome.


The heterologous nucleotide sequence encoding the coronavirus S protein may be produced by inserting the coronavirus S protein gene from different variants into PIV5 canine parainfluenza virus (CPI) vector: CVXGA1, 3, 4, 5, 6, 13, 14 and 16.2. PIV5-based vaccine vectors encoding the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins


PIV5 canine parainfluenza virus (CPI) vaccine vectors encoding SARS-COV-2 variants of concern or variants of interest are disclosed herein. The PIV5-based vaccine vectors may comprise inserting the Spike (S) protein gene from different variants into PIV5 CPI vector: CVXGA1, 3, 4, 5, 6, 13, 14 and 16.


To improve vaccine efficacy, the SARS-CoV-2 nucleocapsid (N) may be inserted between the HN and L gene junction in addition to the SARS-CoV-2 spike (S) inserted at the SH and HN junction. In studies disclosed herein, the expression of both the S and N proteins of SARS-CoV-2 have been shown to offer additional protection for the vaccine especially the cellular immune responses offered by the N protein.


Since the CPI-S+N has reduced titer/yield, the construct may be further modified by moving the SARS-CoV-2 N protein gene to the PIV5 CPI SH gene location as SH deletion has been shown not impacting virus growth. CVXGA7 was constructed to have the N and S genes from SARS-CoV-2 inserted into the CPIΔSH backbone to produce CPIΔSH-N+S.


The mutations in the V/P gene, S157F and S308A, have been shown previously to increase viral polymerase activities and improve viral titer/yield (Timani K A, Sun D, Sun M, et al. A single amino acid residue change in the P protein of parainfluenza virus 5 elevates viral gene expression. J Virol. 2008; 82(18):9123-9133. doi:10.1128/JVI.00289-08; Sun D, Luthra P, Li Z, He B. PLK1 down-regulates parainfluenza virus 5 gene expression. PLoS Pathog., 5(7):e1000525 (2009)). Mutations S157F and S308A are herein introduced into the CPI V/P gene to produce CVXGA10 (CPI-S-PLK) and CVXGA12 (CPIΔSH-S-PLK) viruses.


A PIV5 viral vaccine of the present invention may also have a mutation, alteration, or deletion in one or more of these eight proteins of the PIV5 genome. For example, a PIV5 viral expression vector may include one or more mutations, including, but not limited to any of those described herein. In some aspects, a combination of two or more (two, three, four, five, six, seven, or more) mutations may be advantageous and may demonstrated enhanced activity.


A mutation includes, but is not limited to, a mutation of the V/P gene, a mutation of the shared N-terminus of the V and P proteins, a mutation of residues 26, 32, 33, 50, 102, and/or 157 of the shared N-terminus of the V and P proteins, a mutation lacking the C-terminus of the V protein, a mutation lacking the small hydrophobic (SH) protein, a mutation of the fusion (F) protein, a mutation of the phosphoprotein (P), a mutation of the large RNA polymerase (L) protein, a mutation incorporating residues from canine parainfluenza virus, and/or a mutation that enhances syncytial formation.


A mutation may include, but is not limited to, rPIV5-V/P-CPI-, rPIV5-CPI-, rPIV5-CPI+, rPIV5V ΔC, rPIV-Rev, rPIV5-RL, rPIV5-P-S157A, rPIV5-P-S308A, rPIV5-L-A1981D and rPIV5-F-5443P, rPIV5-MDA7, rPIV5 ΔSH-CPI-, rPIV5 ΔSH-Rev, and combinations thereof.


PIV5 can infect cells productively with little cytopathic effect (CPE) in many cell types. In some cell types, PIV5 infection causes formation of syncytia, i.e., fusion of many cells together, leading to cell death. A mutation may include one or more mutations that promote syncytia formation (see, for example Paterson et al., 2000, Virology; 270:17-30).


The V protein of PIV5 plays a critical role in blocking apoptosis induced by virus. Recombinant PIV5 lacking the conserved cysteine-rich C-terminus (rPIV5V ΔC) of the V protein induces apoptosis in a variety of cells through an intrinsic apoptotic pathway, likely initiated through endoplasmic reticulum (ER)-stress (Sun et al., 2004, J Virol; 78:5068-5078). Mutant recombinant PIV5 with mutations in the N-terminus of the V/P gene products, such as rPIV5-CPI-, also induce apoptosis (Wansley and Parks, 2002, J Virol; 76:10109-10121). A mutation includes, but is not limited to, rPIV5 ΔSH, rPIV5-CPI-, rPIV5VΔC, and combinations thereof.


In some embodiments, PIV5-based vaccine vectors of the present invention are chosen from Table 4.


Also included in the present invention are virions and infectious viral particles that include a PIV5 genome including a heterologous nucleotide sequence encoding a coronavirus S protein, including but not limited to the S protein of SARS-CoV-2.


Also included in the present invention are compositions including one or more of the PIV5 viral constructs or virions, as described herein. Such a composition may include a pharmaceutically acceptable carrier. As used, a pharmaceutically acceptable carrier refers to one or more compatible solid or liquid fillers, diluents or encapsulating substances which are suitable for administration to a human or other vertebrate animal. Such a carrier may be pyrogen free. The present invention also includes methods of making and using the viral vectors and compositions described herein.


The compositions of the present disclosure may be formulated in pharmaceutical preparations in a variety of forms adapted to the chosen route of administration. One of skill will understand that the composition will vary depending on mode of administration and dosage unit.


The agents of this invention can be administered in a variety of ways, including, but not limited to, intravenous, topical, oral, intranasal, subcutaneous, intraperitoneal, intramuscular, and intratumor deliver. In some aspects, the agents of the present invention may be formulated for controlled or sustained release. One advantage of intranasal immunization is the potential to induce a mucosal immune response.


IV. PIV5 Vaccine Virus Sequences


The vaccine virus sequences from the constructs in Table 1 are listed below. The inserted N of SARS-CoV-2 sequences are lower cased and underlined and the inserted S of SARS-CoV-2 sequences are in the lower cased sequences:


1. CVL34


The nucleic acid sequence for CVL34 is:











(SEQ ID NO: 61)



ACCAGGGGGAAAACGAAGTGGTGACTCAAATCATCGAAGACCCTC






GAGATTACATAGGTCCGGAACCTATGGCCTTCGTGACCGACCTCG






AGTCAGAGTAGTTCAATAAGGACCTATCAAGTTTGGGCAATTTTT






CGTCCCCGACACAAAAATGTCATCCGTGCTTAAAGCATATGAGCG






ATTCACACTCACTCAAGAACTGCAAGATCAGAGTGAGGAAGGTAC






AATCCCACCTACAACACTAAAACCGGTAATCAGGGTATTTATACT






AACCTCTAATAACCCAGAGCTAAGATCCCGGCTTCTTCTATTCTG






CCTACGGATTGTTCTCAGTAATGGTGCAAGGGATTCCCATCGCTT






TGGAGCATTACTTACAATGTTTTCGCTACCATCAGCCACAATGCT






CAATCATGTCAAATTAGCTGACCAGTCACCAGAAGCTGATATCGA






AAGGGTAGAGATCGATGGCTTTGAGGAGGGATCATTCCGCTTAAT






CCCCAATGCTCGTTCAGGTATGAGCCGTGGAGAGATCAATGCCTA






TGCTGCACTTGCAGAAGATCTACCTGACACACTAAACCATGCAAC






ACCTTTTGTTGATTCCGAAGTCGAGGGAACTGCATGGGATGAGAT






TGAGACTTTCTTAGATATGTGTTACAGTGTCCTAATGCAGGCATG






GATAGTGACTTGCAAGTGCATGACTGCGCCAGACCAACCTGCTGC






TTCTATTGAGAAACGCCTGCAAAAATATCGTCAGCAAGGCAGGAT






CAACCCGAGATATCTCCTGCAACCGGAGGCTCGAAGAATAATCCA






GAATGTAATCCGAAAGGGAATGGTGGTCAGACATTTCCTCACCTT






TGAACTGCAGCTTGCCCGAGCACAAAGCCTTGTATCAAATAGGTA






TTATGCTATGGTAGGGGATGTTGGAAAGTATATAGAGAATTGTGG






AATGGGAGGCTTCTTTTTGACACTAAAATATGCATTAGGAACCAG






ATGGCCCACACTTGCTTTAGCTGCATTTTCAGGAGAGCTAACAAA






GCTAAAGTCCCTCATGGCATTATACCAGACCCTTGGTGAGCAGGC






CCGATATTTGGCCCTATTGGAGTCACCACATTTGATGGATTTTGC






TGCAGCAAACTACCCACTGCTATATAGCTATGCTATGGGAATAGG






CTATGTGTTAGATGTCAACATGAGGAACTACGCTTTCTCCAGATC






ATACATGAATAAGACATATTTCCAATTGGGAATGGAAACTGCAAG






AAAACAACAGGGTGCAGTTGACATGAGGATGGCAGAAGATCTCGG






TCTAACTCAAGCCGAACGCACCGAGATGGCAAATACACTTGCCAA






ATTGACCACAGCAAATCGAGGGGCAGACACCAGGGGAGGAGTCAA






CCCGTTCTCATCTATCACTGGGACAACTCAGGTGCCCGCTGCAGC






AACAGGTGACACATTCGAGAGTTACATGGCAGCGGATCGACTGAG






GCAGAGATATGCTGATGCAGGCACCCACGATGATGAGATGCCACC






ATTGGAAGAGGAGGAAGAGGACGACACATCTGCAGGTCCACGCAC






TGGACTAACTCTTGAACAAGTGGCCTTGGACATCCAGAACGCAGC






AGTTGGAGCTCCCATCCATACAGATGACCTGAATGCCGCACTGGG






TGATCTTGACATCTAGACAATTCAGATCCCAATCTTAAATCGACA






CACCTAATTGACCAGTTAGATGGAACTACAGTGGATTCCATAAGG






TTCCTGCCTACCATCGGCTTTTAAGAAAAAAATAGGCCCGGACGG






GTTAGCAACAAGCGACTGCCGATGCCAATAACACAATCCACAATC






TACAATGGATCCCACTGATCTGAGCTTCTCCCCAGATGAGATCAA






TAAGCTCATAGAGACAGGCCTGAATACTGTGGAGTATTTTACTTC






CCAACAAGTCACAGGAACATCCTCTCTTGGAAAGAATACAATACC






ACCAGGGGTCACAGGACTACTAACCAATGCTGCAGAGGCAAAGAT






CCAAGAGTCAACCAACCATCAGAAGGGTTCAGTTGGTGGGGGCGC






AAAACCAAAGAAACCGCGACCAAAAATTGCCATTGTGCCAGCAGA






TGACAAAACGGTGCCCGGAAAGCCGATCCCAAACCCTCTATTAGG






TCTGGACTCCACCCCGAGCACCCAAACTGTGCTTGATCTAAGTGG






GAAAACATTACCATCAGGATCCTATAAGGGGGTTAAACTTGCGAA






ATTTGGAAAAGAAAATCTGATGACACGGTTCATCGAGGAACCCAG






AGAGAATCCTATCGCAACCAATTCCCCCATCGATTTTAAGAGGGG






CAGGGATACCGGCGGGTTCCATAGAAGGGAGTACTCAATCGGATG






GGTGGGAGATGAAGTCAAGGTCACTGAGTGGTGCAATCCATCCTG






TTCTCCAATCACCGCTGCAGCAAGGCGATTTGAATGCACTTGTCA






CCAGTGTCCAGTCACTTGCTCTGAATGTGAACGAGATACTTAATA






CAGTGAGAAATTTGGACTCTCGGATGAATCAACTGGAGACAAAAG






TAGATCGCATTCTCTCATCTCAGTCTCTAATCCAGACCATCAAGA






ATGACATAGTTGGACTTAAAGCAGGGATGGCTACTTTAGAAGGAA






TGATTACAACTGTGAAAATCATGGACCCGGGAGTTCCCAGTAATG






TTACTGTGGAAGATGTACGCAAGAAACTAAGTAACCATGCTGTTG






TTGTGCCAGAATCATTCAATGATAGTTTCTTGACTCAATCTGAAG






ATGTAATTTCACTTGATGAGTTGGCTCGACCAACTGCAACAAGTG






TTAAGAAGATTGTCAGGAAGGTTCCTCCTCAGAAGGATCTGACTG






GATTGAAGATCACACTAGAGCAATTGGCAAAGGATTGCATCAGCA






AACCGAAGATGAGGGAAGAGTATCTCCTCAAAATCAACCAGGCTT






CCAGTGAGGCTCAGCTAATTGACCTCAAGAAAGCAATCATCCGCA






GTGCAATTTGATCAAGAAACACCCAATTACACTACACTGGTATGA






CACTGTACTAACCCTGAGGGTTTTAGAAAAAACGATTAACGATAA






ATAAGCCCGAACACTACACACCACCCGAGGCAGCCATGCCATCCA






TCAGCATCCCCGCAGACCCCACCAATCCACGTCAATCAATAAAAG






CGTTCCCAATTGTGATCAACCGTGATGGGGGTGAGAAAGGTCGCT






TGGTTAAACAACTACGCACAACCTACTTGAATGACCTAGATACTC






ATGAGCCACTGGTGACATTCGTAAATACTTATGGATTCATCTACG






AACAGGATCGGGGAAATACCATTGTCGGAGAGGATCAACATGGGA






AGAAAAGAGAGGCTGTGACTGCTGCAATGGTTACCCTTGGATGTG






GGCCTAATCTACCATCATTAGGGAATGTCCTGGGACAACTGAGTG






AATTCCAGGTCATTGTTAGGAAGACATCCAGCAAAGCGGAAGAGA






TGGTCTTTGAAATTGTTAAGTATCCGAGAATATTTCGGGGTCATA






CATTAATCCAGAAAGGACTAGTCTGTGTCTCCGCAGAAAAATTTG






TTAAGTCACCAGGGAAAGTACAATCTGGAATGGACTATCTCTTCA






TTCCGACATTTCTGTCAGTGACTTACTGTCCAGCTGCAATCAAAT






TTCAGGTACCTGGCCCCATGTTGAAAATGAGATCAAGATACACTC






AGAGCTTACAACTTGAACTAATGATAAGAATCCTGTGTAAGCCCG






ATTCGCCACTTATGAAGGTCCATATCCCTGACAAGGAAGGAAGAG






GATGTCTTGTATCAGTATGGTTGCATGTATGCAATATCTTCAAAT






CAGGAAACAAGAATGGCAGTGAGTGGCAGGAATACTGGATGAGAA






AGTGTGCTAACATGCAACTTGAAGTGTCGATTGCAGATATGTGGG






GACCAACTATCATAATTCATGCCAGAGGTCACATTCCCAAAAGTG






CTAAGTTGTTTTTTGGAAAGGGTGGATGGAGCTGCCATCCACTTC






ACGAAGTTGTTCCAAGTGTCACTAAAACACTATGGTCCGTGGGCT






GTGAGATTACAAAGGCGAAGGCAATAATACAAGAGAGTAGCATCT






CTCTTCTCGTGGAGACTACTGACATCATAAGTCCAAAAGTCAAAA






TTTCATCTAAGCATCGCCGCTTTGGGAAATCAAATTGGGGTCTGT






TCAAGAAAACCAAATCACTGCCCAACCTGACGGAGCTGGAATGAC






TGACCCCCAATCGAGACTACACCACCTCAAACTATAGGTGGGTGG






TACCTCAGTGATTAATCTCGTAAGCACTGATCGTAGGCTACAACA






CACTAATATTATCCAGATTAGAGAGCTTAATTAGCTCTGTATTAA






TAATAACACTACTATTCCAATAACTGGAATCACCAGCTTGATTTA






TCTCCAAAATGATTCAAAGAAAACAAATCATATTAAGACTATCCT






AAGCACGAACCCATATCGTCCTTCAAATCATGGGTACTATAATTC






AATTTCTGGTGGTCTCCTGTCTATTGGCAGGAGCAGGCAGTCTTG






ATCCAGCAGCCCTCATGCAAATCGGTGTCATTCCAACAAATGTCC






GGCAACTTATGTATTATACTGAGGCCTCATCAGCATTCATTGTTG






TGAAGTTAATGCCTACAATTGACTCGCCGATTAGTGGATGTAATA






TAACATCAATTTCAAGCTATAATGCAACAGTGACAAAACTCCTAC






AGCCGATCGGTGAGAATTTGGAGACGATTAGGAACCAGTTGATTC






CAACTCGGAGGAGACGCCGGTTTGCAGGGGTGGTGATTGGATTAG






CTGCATTAGGAGTAGCTACTGCCGCACAGGTCACTGCCGCAGTAG






CACTAGTAAAGGCAAATGAAAATGCTGCGGCTATACTCAATCTCA






AAAATGCAATCCAAAAAACAAATGCAGCAGTTGCAGATGTGGTCC






AGGCCACACAATCACTAGGAACAGCAGTTCAAGCAGTTCAAGATC






ACATAAACAGTGTGGTAAGTCCAGCAATTACAGCAGCCAATTGTA






AAGCCCAAGATGCTATCATTGGCTCAATCCTCAATCTCTATTTGA






CCGAGTTGACAACTATCTTCCACAATCAAATTACAAACCCTGCAT






TGAGTCCTATTACAATTCAAGCTTTAAGGATCCTACTAGGGAGTA






CCTTGCCGACTGTGGTCGAAAAATCTTTCAATACCCAGATAAGTG






CGGCTGAGCTTCTCTCATCAGGGTTATTGACAGGCCAGATTGTGG






GATTAGATTTGACCTATATGCAGATGGTCATAAAAATTGAGCTGC






CAACTTTAACTGTACAACCTGCAACCCAGATCATAGATCTGGCCA






CCATTTCTGCATTCATTAACAATCAAGAAGTCATGGCCCAATTAC






CAACACGTGTTATTGTGACTGGCAGCTTGATCCAAGCCTATCCCG






CATCGCAATGCACTATTACACCCAACACTGTGTACTGTAGGTATA






ATGATGCCCAAGTACTCTCAGATGATACGATGGCTTGCCTCCAAG






GTAACTTGACAAGATGCACCTTCTCTCCAGTGGTTGGGAGCTTTC






TCACTCGATTCGTGCTGTTCGATGGAATAGTTTATGCAAATTGCA






GGTCGATGTTGTGCAAGTGCATGCAGCCTGCTGCTGTGATCCTAC






AGCCGAGTTCATCCCCTGTAACTGTCATTGACATGTACAAATGTG






TGAGTCTGCAGCTTGACAATCTCAGATTCACCATCACTCAATTGG






CCAATGTAACCTACAATAGCACCATCAAGCTTGAAACATCCCAGA






TCTTGCCTATTGATCCGTTGGATATATCCCAGAATCTAGCTGCGG






TGAATAAGAGTCTAAGTGATGCACTACAACACTTAGCACAAAGTG






ACACATACCTTTCTGCAATCACATCAGCTACGACTACAAGTGTAT






TATCCATAATAGCAATCTGTCTTGGATCGTTAGGTTTAATATTAA






TAATCTTGCTCAGTGTAGTTGTGTGGAAGTTATTGACCATTGTCG






CTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAATTCAG






CATTCCACCACTCACGATCTGATCTCAGTGAGAAAAATCAACCTG






CAACTCTTGGAACAAGATAAGACAGTCATCCATTAGTAATTTTTA






AGAAAAAAACGATAGGACCGAAACTAGTATTGAAAGAACCGTCTC






GGTCAATCTAGGTAATCGAGCTGCTACCGTCTCGGAAAGCTCAAA






TCATGCTGCCTGATCCGGAAGATCCGGAAAGCAAAAAAGCTACAA






GGAGAACAGGAAACCTAATTATCTGCTTCCTATTCATCTTCTTTC






CGTTTGTAAACTTCATTGTTCCAACTCTAAGACACTTGCTGTCCT






AACACCTGCTATAGGCTATCCACTGCATCATCTCTTTTTAAGAAA






AAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCCGGTGCCAA






CAACACAATCCACAATCTACAGTCGACGCGGCCGCCatgttcgtc






ttcctggtcctgctgcctctggtctcctcacagtgcgtcaatctg






acaactcggactcagctgccacctgcttatactaatagcttcacc






agaggcgtgtactatcctgacaaggtgtttagaagctccgtgctg






cactctacacaggatctgtttctgccattctttagcaacgtgacc






tggttccacgccatccacgtgagcggcaccaatggcacaaagcgg






ttcgacaatcccgtgctgccttttaacgatggcgtgtacttcgcc






tctaccgagaagagcaacatcatcagaggctggatctttggcacc






acactggactccaagacacagtctctgctgatcgtgaacaatgcc






accaacgtggtcatcaaggtgtgcgagttccagttttgtaatgat






cccttcctgggcgtgtactatcacaagaacaataagagctggatg






gagtccgagtttagagtgtattctagcgccaacaactgcacattt






gagtacgtgagccagcctttcctgatggacctggagggcaagcag






ggcaatttcaagaacctgagggagttcgtgtttaagaatatcgac






ggctacttcaaaatctactctaagcacacccccatcaacctggtg






cgcgacctgcctcagggcttcagcgccctggagcccctggtggat






ctgcctatcggcatcaacatcacccggtttcagacactgctggcc






ctgcacagaagctacctgacacccggcgactcctctagcggatgg






accgccggcgctgccgcctactatgtgggctacctccagccccgg






accttcctgctgaagtacaacgagaatggcaccatcacagacgca






gtggattgcgccctggaccccctgagcgagacaaagtgtacactg






aagtcctttaccgtggagaagggcatctatcagacatccaatttc






agggtgcagccaaccgagtctatcgtgcgctttcctaatatcaca






aacctgtgcccatttggcgaggtgttcaacgcaacccgcttcgcc






agcgtgtacgcctggaataggaagcggatcagcaactgcgtggcc






gactatagcgtgctgtacaactccgcctctttcagcacctttaag






tgctatggcgtgtcccccacaaagctgaatgacctgtgctttacc






aacgtctacgccgattctttcgtgatcaggggcgacgaggtgcgc






cagatcgcccccggccagacaggcaagatcgcagactacaattat






aagctgccagacgatttcaccggctgcgtgatcgcctggaacagc






aacaatctggattccaaagtgggcggcaactacaattatctgtac






cggctgtttagaaagagcaatctgaagcccttcgagagggacatc






tctacagaaatctaccaggccggcagcaccccttgcaatggcgtg






gagggctttaactgttatttcccactccagtcctacggcttccag






cccacaaacggcgtgggctatcagccttaccgcgtggtggtgctg






agctttgagctgctgcacgccccagcaacagtgtgcggccccaag






aagtccaccaatctggtgaagaacaagtgcgtgaacttcaacttc






aacggcctgaccggcacaggcgtgctgaccgagtccaacaagaag






ttcctgccatttcagcagttcggcagggacatcgcagataccaca






gacgccgtgcgcgacccacagaccctggagatcctggacatcaca






ccctgctctttcggcggcgtgagcgtgatcacacccggcaccaat






acaagcaaccaggtggccgtgctgtatcaggacgtgaattgtacc






gaggtgcccgtggctatccacgccgatcagctgaccccaacatgg






cgggtgtacagcaccggctccaacgtcttccagacaagagccgga






tgcctgatcggagcagagcacgtgaacaattcctatgagtgcgac






atcccaatcggcgccggcatctgtgcctcttaccagacccagaca






aactctcccagaagagcccggagcgtggcctcccagtctatcatc






gcctataccatgtccctgggcgccgagaacagcgtggcctactct






aacaatagcatcgccatcccaaccaacttcacaatctctgtgacc






acagagatcctgcccgtgtccatgaccaagacatctgtggactgc






acaatgtatatctgtggcgattctaccgagtgcagcaacctgctg






ctccagtacggcagcttttgtacccagctgaatagagccctgaca






ggcatcgccgtggagcaggataagaacacacaggaggtgttcgcc






caggtgaagcaaatctacaagaccccccctatcaaggactttggc






ggcttcaatttttcccagatcctgcctgatccatccaagccttct






aagcggagctttatcgaggacctgctgttcaacaaggtgaccctg






gccgatgccggcttcatcaagcagtatggcgattgcctgggcgac






atcgcagccagggacctgatctgcgcccagaagtttaatggcctg






accgtgctgccacccctgctgacagatgagatgatcgcacagtac






acaagcgccctgctggccggcaccatcacatccggaTggaccTTc






ggcgcaggagccgccctccagatcccctttgccatgcagatggcc






tataggttcaacggcatcggcgtgacccagaatgtgctgtacgag






aaccagaagctgatcgccaatcagtttaactccgccatcggcaag






atccaggacagcctgtcctctacagccagcgccctgggcaagctc






caggatgtggtgaatcagaacgcccaggccctgaataccctggtg






aagcagctgagcagcaacttcggcgccatctctagcgtgctgaat






gacatcctgagccggctggacaaggtggaggcagaggtgcagatc






gaccggctgatcaccggccggctccagagcctccagacctatgtg






acacagcagctgatcagggccgccgagatcagggccagcgccaat






ctggcagcaaccaagatgtccgagtgcgtgctgggccagtctaag






agagtggacttttgtggcaagggctatcacctgatgtccttccct






cagtctgccccacacggcgtggtgtttctgcacgtgacctacgtg






cccgcccaggagaagaacttcaccacagcccctgccatctgccac






gatggcaaggcccactttccaagggagggcgtgttcgtgtccaac






ggcacccactggtttgtgacacagcgcaatttctacgagccccag






atcatcaccacagacaacaccttcgtgagcggcaactgtgacgtg






gtcatcggcatcgtgaacaataccgtgtatgatccactccagccc






gagctggacagctttaaggaggagctggataagtatttcaagaat






cacacctcccctgacgtggatctgggcgacatcagcggcatcaat






gcctccgtggtgaacatccagaaggagatcgaccgcctgaacgag






gtggctaagaatctgaacgagagcctgatcgacctccaggagctg






ggcaagtatgagcagtacatcaagtggccctggtacatctggctg






ggcttcatcgccggcctgatcgccatcgtgatggtgaccatcatg






ctgtgctgtatgacatcctgctgttcttgcctgaagggctgctgt






agctgtggctcctgctgtAAGTTATTGACCATTGTCGTTGCTAAT






CGAAATAGAATGGAGAATTTTGTTTATCATAAATGAACGCGTGCT






AGCCTCCTGCCATACTTCCTACTCACATCATATCTATTTTAAAGA






AAAAATAGGCCCGAACACTAATCGTGCCGGCAGTGCCACTGCACA






CACAACACTACACATACAATACACTACAATGGTTGCAGAAGATGC






CCCTGTTAGGGGCACTTGCCGAGTATTATTTCGAACAACAACTTT






AATTTTTCTATGCACACTATTAGCATTAAGCATCTCTATCCTTTA






TGAGAGTTTAATAACCCAAAAGCAAATCATGAGCCAAGCAGGCTC






AACTGGATCTAATTCTAGATTAGGAAGTATCACTGATCTTCTTAA






TAATATTCTCTCTGTCGCAAATCAGATTATATATAACTCTGCAGT






CGCTCTACCTCTACAATTGGACACTCTTGAATCAACACTCCTTAC






AGCCATTAAGTCTCTTCAAACAAGTGACAAGCTAGAACAGAACTG






CTCGTGGGGTGCTGCACTGATTAATGATAATAGATACATTAATGG






CATCAATCAGTTCTATTTCTCAATTGCTGAGGGTCGCAAGCTGAC






ACTTGGCCCACTTCTTAATATACCTAGTTTCATTCCAACTGCCAC






GACACCAGAGGGCTGCACCAGGATCCCATCATTCTCGCTCACCAA






GACACACTGGTGTTATACACACAATGTTATCCTGAATGGATGCCA






GGATCATGTATCCTCAAATCAATTTGTTTCCATGGGAATCATTGA






ACCCACTTCTGCCGGGTTTCCATCCTTTCGAACCCTAAAGACTCT






ATATCTCAGCGATGGGGTCAATCGTAAGAGCTGCTCTATCAGTAC






AGTTCCGGGGGGTTGTATGATGTACTGTTTCGTCTCTACTCAACC






AGAGAGGGATGACTACTTTTCTACCGCTCCTCCAGAACAACGAAT






TATTATAATGTACTATAATGATACAATCGTGGAGCGCATAATTAA






TCCACCCGGGGTACTAGATGTATGGGCAACATTGAACCCAGGAAC






AGGAAGCGGGGTATATTATTTAGGTTGGGTACTCTTTCCAATATA






TGGCGGCGTGATTAAAGATACGAGTTTATGGAATAATCAAGCAAA






TAAATACTTTATCCCCCAGATGGTTGCTGCTCTCTGCTCACAAAA






CCAGGCAACTCAAGTCCAAAATGCTAAGTCATCATACTATAGCAG






CTGGTTTGGCAATCGAATGATTCAGTCTGGGATCCTGGCATGTCC






TCTTCAACAGGATCTAACCAATGAGTGTTTAGTTCTGCCCTTTTC






TAATGATCAGGTGCTTATGGGTGCTGAAGGGAGATTATACATGTA






TGGTGACTCGGTGTATTACTACCAAAGAAGCAATAGTTGGTGGCC






TATGACCATGCTGTATAAGGTAACCATAACATTCACTAATGGTCA






GCCATCTGCTATATCAGCTCAGAATGTGCCCACACAGCAGGTCCC






TAGACCTGGGACAGGAAGCTGCTCTGCAACAAATAGATGTCCCGG






TTTTTGCTTGAAAGGAGTGTATGCTGATGCCTGGTTACTGACCAA






CCCTTCGTCTACCAGTACATTTGGATCAGAAGCAACCTTCACTGG






TTCTTATCTCAACGCAGCAACTCAGCGTATCAATCCGACGATGTA






TATCGCGAACAACACACAGATCATAAGCTCACAGCAATTTGGATC






AAGCGGTCAAGAAGCAGCATATGGCCACACAACTTGTTTTAGGGA






CACAGGCTCTGTTATGGTATACTGTATCTATATTATTGAATTGTC






CTCATCTCTCTTAGGACAATTTCAGATTGTCCCATTTATCCGTCA






GGTGACACTATCCTAAAGGCAGAAGCCTTCAGGTCTGACCCAGCC






AATCAAAGCATTATACCAGACCATGGCCTACCATCGGCTTTAAAG






AAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGGCGGCCGCGAA






TTCGCCACCatgtcagataacggaccacagaaccagaggaacgca







cccaggattactttcggaggaccaagcgatagcaccgggagcaac








cagaatggagagcggagcggagcaagatccaagcagagacggccc








cagggcctgccaaacaataccgcatcctggttcaccgccctgaca








cagcacggcaaggaggacctgaagtttccaaggggacagggagtg








cctatcaacaccaatagctcccctgacgatcagatcggctactat








aggagggcaacaaggagaatcaggggaggcgacggcaagatgaag








gatctgagcccacgctggtacttctactatctgggaaccggacct








gaggcaggcctgccatatggcgccaacaaggacggaatcatctgg








gtggcaaccgagggcgccctgaacacaccaaaggatcacatcggc








acaagaaatcccgccaacaatgcagcaatcgtgctgcagctgcca








cagggaaccacactgcccaagggcttttacgcagagggctctcgg








ggaggcagccaggcatctagcagatcctctagccggagcagaaac








tcctctaggaattccaccccaggaagctccaggggcacatcccct








gcccgcatggcaggaaacggaggcgacgccgccctggccctgctg








ctgctggatcgcctgaatcagctggagtccaagatgtctggcaag








ggacagcagcagcagggacagaccgtgacaaagaagtccgccgcc








gaggcctctaagaagccaaggcagaagcgcaccgccacaaaggcc








tacaacgtgacccaggccttcggcaggcgcggaccagagcagaca








cagggcaattttggcgaccaggagctgatcaggcagggaaccgat








tataagcactggcctcagatcgcccagttcgccccatctgccagc








gccttctttggcatgtctagaatcggcatggaggtgacccccagc








ggcacatggctgacctacacaggcgccatcaagctggacgataag








gaccctaacttcaaggatcaggtcatcctgctgaacaagcacatc








gacgcctataagacctttccccctacagagcccaagaaggacaag








aagaagaaggccgatgagacacaggccctgcctcagaggcagaag








aagcagcagaccgtgacactgctgccagccgccgatctggacgat








ttctccaaacagctgcagcagagcatgtccagtgccgactccacc








caggcttgatgaTGAGGTACCTGCGGCCGCCTAAGGTCGACTCAT







GGAATGCATACCAAACATTATTGACACTAATGACACACAAAATTG






GTTTTAAGAAAAACCAAGAGAACAATAGGCCAGAATGATGGCTGG






GTCTCGGGAGATATTACTCCCTGAAGTCCATCTCAATTCACCAAT






TGTAAAGCATAAGCTATACTATTACATTCTACTTGGAAACCTCCC






AAATGAGATCGACATTGACGATTTAGGTCCATTACATAATCAAAA






TTGGAATCAAATAGCACATGAAGAGTCTAACTTAGCCCAACGCTT






GGTAAATGTAAGAAATTTTCTAATTACCCACATCCCTGATCTTAG






AAAGGGCCATTGGCAAGAGTATGTCAATGTAATACTGTGGCCGCG






AATTCTTCCCTTGATCCCGGATTTTAAAATCAATGACCAATTGCC






TCTACTCAAAAATTGGGACAAGTTAGTTAAAGAATCATGTTCAGT






AATCAATGCGGGTACTTCCCAGTGCATTCAGAATCTCAGCTATGG






ACTGACAGGTCGTGGGAACCTCTTTACACGATCACGTGAACTCTC






TGGTGACCGCAGGGATATTGATCTTAAGACGGTTGTGGCAGCATG






GCATGACTCAGACTGGAAAAGAATAAGTGATTTTTGGATTATGAT






CAAATTCCAGATGAGACAATTAATTGTTAGGCAAACAGATCATAA






TGATCCTGATTTAATCACGTATATCGAAAATAGAGAAGGCATAAT






CATCATAACCCCTGAACTGGTAGCATTATTTAACACTGAGAATCA






TACACTAACATACATGACCTTTGAAATTGTACTGATGGTTTCAGA






TATGTACGAAGGTCGTCACAACATTTTATCACTATGCACAGTTAG






CACTTACCTGAATCCTCTGAAGAAAAGAATAACATATTTATTGAG






CCTTGTAGATAACTTAGCTTTTCAGATAGGTGATGCTGTATATAA






CATAATTGCTTTGCTAGAATCCTTTGTATATGCACAGTTGCAAAT






GTCAGATCCCATCCCAGAACTCAGAGGACAATTCCATGCATTCGT






ATGTTCTGAGATTCTTGATGCACTAAGGGGAACTAATAGTTTCAC






CCAGGATGAATCAAGAACTGTGACAACCAATTTGATATCCCCATT






CCAAGATCTGACCCCAGATCTTACGGCTGAATTGCTCTGTATAAT






GAGGCTTTGGGGACACCCCATGCTCACCGCCAGTCAAGCTGCGGG






AAAGGTACGCGAGTCCATGTGTGCTGGAAAAGTATTAGACTTTCC






CACCATTATGAAAACACTAGCCTTTTTCCATACTATTCTGATCAA






TGGATACAGGAGGAAGCATCATGGAGTATGGCCACCCTTAAACTT






ACCGGGTAATGCTTCAAAGGGTCTCACGGAACTTATGAATGACAA






TACTGAGATAAGCTATGAATTCACACTTAAGCATTGGAAGGAAAT






CTCTCTTATAAAATTCAAGAAATGTTTTGATGCAGACGCAGGTGA






GGAACTCAGTATATTTATGAAAGATAAAGCAATTAGTGCCCCAAA






ACAAGATTGGATGAGTGTGTTTAGAAGAAGCCTAATCAAACAGCG






CCATCAGCATCATCAGGTCCCCCTACCAAATCCATTCAATCGACG






GCTATTGCTAAACTTTCTCGGAGATGACAAATTCGACCCGAATGT






GGAGCTACAGTATGTAACATCAGGTGAGTATCTACATGATGACAC






GTTTTGTGCATCATATTCACTAAAAGAGAAGGAAATTAAACCTGA






TGGTCGAATTTTTGCAAAGTTGACTAAGAGAATGAGATCATGTCA






AGTTATAGCAGAATCTCTTTTAGCGAACCATGCTGGGAAGTTAAT






GAAAGAGAATGGTGTTGTGATGAATCAGCTATCATTAACAAAATC






ACTATTAACAATGAGTCAGATTGGAATAATATCCGAGAAAGCTAG






AAAATCGACTCGAGATAACATAAATCAACCTGGTTTCCAGAATAT






CCAGAGAAATAAATCACATCACTCCAAGCAAGTCAATCAGCGAGA






TCCAAGTGATGACTTTGAATTGGCAGCATCTTTTTTAACTACTGA






TCTCAAAAAATATTGTTTACAATGGAGGTACCAGACAATTATCCC






ATTTGCTCAATCATTAAACAGAATGTATGGTTATCCTCATCTCTT






TGAGTGGATTCACTTACGGCTAATGCGTAGTACACTTTACGTGGG






GGATCCCTTCAACCCACCAGCAGATACCAGTCAATTTGATCTAGA






TAAAGTAATTAATGGAGATATCTTCATTGTATCACCCAGAGGTGG






AATTGAAGGGCTATGTCAAAAGGCTTGGACAATGATATCTATCTC






TGTGATAATTCTATCTGCCACAGAGTCTGGCACACGAGTAATGAG






TATGGTGCAGGGAGATAATCAAGCAATTGCTGTCACCACACGAGT






ACCAAGGAGCCTGCCGACTCTTGAGAAAAAGACTATTGCTTTTAG






ATCTTGTAATCTATTCTTTGAGAGGTTAAAATGTAATAATTTTGG






ATTAGGTCACCATTTGAAAGAACAAGAGACTATCATTAGTTCTCA






CTTCTTTGTTTATAGCAAGAGAATATTCTATCAGGGGAGGATTCT






AACGCAAGCCTTAAAAAATGCTAGTAAGCTCTGCTTGACAGCTGA






TGTCCTAGGAGAATGTACCCAATCATCATGTTCTAATCTTGCAAC






TACTGTCATGAGGTTAACTGAGAATGGTGTTGAAAAAGATATCTG






TTTCTACTTGAATATCTATATGACCATCAAACAGCTCTCCTATGA






TATCATCTTCCCTCAAGTGTCAATTCCTGGAGATCAGATCACATT






AGAATACATAAATAATCCACACCTGGTATCACGATTGGCTCTTCT






GCCATCCCAGCTAGGAGGTCTAAACTACCTGTCATGCAGTAGGCT






GTTCAATCGAAACATAGGCGACCCGGTGGTTTCCGCAGTTGCAGA






TCTTAAGAGATTAATTAAATCAGGATGTATGGATTACTGGATCCT






TTATAACTTATTAGGGAGAAAACCGGGAAACGGCTCATGGGCTAC






TTTAGCAGCTGACCCGTACTCAATCAATATAGAGTATCAATACCC






CCCAACTACAGCTCTTAAGAGGCACACCCAACAAGCTCTGATGGA






ACTCAGTACGAATCCAATGTTACGTGGCATATTCTCTGACAATGC






ACAGGCAGAAGAAAATAATCTTGCTAGATTTCTCCTGGATAGGGA






GGTGATCTTTCCGCGTGTAGCTCACATCATCATTGAGCAAACCAG






TGTCGGGAGGAGAAAACAGATTCAAGGATATTTGGATTCAACTAG






ATCGATAATGAGTAAATCACTAGAAATTAAGCCCTTGTCCAATAG






GAAGCTTAATGAAATACTGGATTACAACATCAATTACCTAGCTTA






CAATTTGGCATTACTCAAGAATGCTATTGAACCTCCGACTTATTT






GAAAGCAATGACTCTTGAAACATGTAGCATCGACATTGCAAGGAG






CCTCCGGAAGCTCTCCTGGGCCCCACTCTTGGGTGGGAGAAATCT






TGAAGGATTAGAGACGCCAGATCCCATTGAAATTACTGCAGGAGC






ATTAATTGTTGGATCGGGCTACTGTGAACAGTGTGCTGCAGGAGA






CAATCGATTCACATGGTTTTTCTTGCCATCTGGTATCGAGATAGG






AGGGGATCCCCGTGATAATCCTCCTATCCGTGTACCGTACATTGG






CTCCAGGACTGATGAGAGGAGGGTAGCCTCAATGGCATACATCAG






GGGTGCCTCGAGTAGCCTAAAAGCAGTTCTTAGACTGGCGGGAGT






GTACATCTGGGCATTCGGAGATACTCTGGAGAATTGGATAGATGC






ACTGGATTTGTCTCACACTAGAGTTAACATCACACTTGAACAGCT






GCAATCCCTCACCCCACTTCCAACCTCTGCCAATCTAACCCATCG






GTTGGATGATGGCACAACTACCCTAAAGTTTACTCCTGCGAGCTC






TTACACCTTTTCAAGTTTCACTCATATATCAAATGATGAGCAATA






CCTGACAATTAATGACAAAACTGCAGATTCAAATATAATCTACCA






ACAGTTAATGATCACTGGACTCGGAATTTTAGAAACATGGAATAA






TCCCCCAATCAATAGAACATTCGAAGAATCTACCCTACATTTGCA






CACTGGTGCATCATGTTGTGTCCGACCTGTGGACTCCTGCATCAT






CTCAGAAGCATTAACAGTCAAGCCACATATTACAGTACCGTACAG






CAATAAATTTGTATTTGATGAAGACCCGCTATCTGAATATGAGAC






TGCAAAACTGGAATCGTTATCATTTCAAGCCCAATTAGGCAACAT






TGATGCTGTAGATATGACAGGTAAATTAACATTATTGTCCCAATT






CACTGCAAGGCAGATTATTAATGCAATCACTGGACTCGATGAGTC






TGTCTCTCTTACTAATGATGCCATTGTTGCATCAGACTATGTCTC






CAATTGGATTAGTGAATGCATGTATACCAAATTAGATGAATTATT






TATGTATTGTGGGTGGGAACTACTATTGGAACTATCCTATCAAAT






GTATTATCTGAGGGTAGTTGGGTGGAGTAATATAGTGGATTATTC






TTACATGATCTTGAGAAGAATCCCGGGTGCAGCATTAAACAATCT






GGCATCTACATTAAGTCATCCAAAACTTTTCCGACGAGCTATCAA






CCTAGATATAGTTGCCCCCTTAAATGCTCCTCATTTTGCATCTCT






GGACTACATCAAGATGAGTGTGGATGCAATACTCTGGGGCTGTAA






AAGAGTCATCAATGTGCTCTCCAATGGAGGGGACTTAGAATTAGT






TGTGACATCTGAAGATAGCCTTATTCTCAGTGACCGATCCATGAA






TCTCATTGCAAGGAAATTAACTTTATTATCACTGATTCACCATAA






TGGTTTGGAACTACCAAAGATTAAGGGGTTCTCTCCTGATGAGAA






GTGTTTCGCTTTGACAGAATTTTTGAGGAAAGTGGTGAACTCAGG






GTTGAGTTCAATAGAGAACCTATCAAATTTTATGTACAATGTGGA






GAACCCACGGCTTGCAGCATTCGCCAGCAACAATTACTACCTGAC






CAGAAAATTATTGAATTCAATACGAGATACTGAGTCGGGTCAAGT






AGCAGTCACCTCATATTATGAATCATTAGAATATATTGATAGTCT






TAAGCTAACCCCACATGTGCCTGGTACCTCATGCATTGAGGATGA






TAGTCTATGTACAAATGATTACATAATCTGGATCATAGAGTCTAA






TGCAAACTTGGAGAAGTATCCAATTCCAAATAGCCCTGAGGATGA






TTCCAATTTCCATAACTTTAAGTTGAATGCTCCATCGCACCATAC






CTTACGCCCATTAGGGTTGTCATCAACTGCTTGGTATAAGGGTAT






AAGCTGTTGCAGGTACCTTGAGCGATTAAAGCTACCACAAGGTGA






TCATTTATATATTGCAGAAGGTAGTGGTGCCAGTATGACAATCAT






AGAATACCTATTCCCAGGAAGAAAGATATATTACAATTCTTTATT






TAGTAGTGGTGACAATCCCCCACAAAGAAATTATGCACCAATGCC






TACTCAGTTCATTGAGAGTGTCCCATACAAGCTCTGGCAAGCACA






CACAGATCAATATCCCGAGATTTTTGAGGACTTCATCCCTCTATG






GAACGGAAATGCCGCCATGACTGACATAGGAATGACAGCTTGTGT






AGAATTCATCATCAATCGAGTCGGCCCAAGGACTTGCAGTTTAGT






ACATGTAGATTTGGAATCAAGTGCAAGCTTAAATCAACAATGCCT






GTCAAAGCCGATAATTAATGCTATCATCACTGCTACAACTGTTTT






GTGCCCTCATGGGGTGCTTATTCTGAAATATAGTTGGTTGCCATT






TACTAGATTTAGTACTTTGATCACTTTCTTATGGTGCTACTTTGA






GAGAATCACTGTTCTTAGGAGCACATATTCTGGTCCAGCTAATCA






TGAGGTTTATTTAATTTGTATCCTTGCCAACAACTTTGCATTCCA






GACTGTCTCGCAGGCAACAGGAATGGCGATGACTTTAACCGATCA






AGGGTTTACTTTGATATCACCTGAAAGAATAAATCAGTATTGGGA






TGGTCACTTGAAGCAAGAACGTATCGTAGCAGAAGCAATTGATAA






GGTGGTTCTAGGAGAAGATGCTCTATTCAATTCGAGTGATAATGA






ATTAATTCTCAAATGTGGAGGGACACCAAATGCACGGAATCTTAT






CGATATCGAGCCAGTCGCAACTTTCATAGAATTTGAACAACTGAT






CTGCACAATGTTGACAACCCACTTGAAGGAAATAATTGATATAAC






AAGGTCTGGAACCCAGGATTATGAAAGTTTATTACTCACTCCTTA






CAATTTAGGTCTTCTTGGTAAAATCAGTACGATAGTGAGATTATT






AACAGAAAGGATTCTAAATCATACTATCAGGAATTGGTTGATCCT






CCCACCTTCGCTCCGGATGATCGTGAAGCAGGACTTGGAATTCGG






CATATTCAGGATTACTTCCATCCTCAATTCTGATCGGTTCCTGAA






GCTTTCTCCAAATAGGAAATACTTGATTACACAATTAACTGCAGG






CTACATTAGGAAATTGATTGAGGGGGATTGTAATATCGATCTAAC






CAGACCTATCCAAAAACAAATCTGGAAAGCATTAGGTTGTGTAGT






CTATTGTCACGATCCAGTAGATCAAAGGGAATCAACAGAGTTTAT






TGATATAAATATTAATGAAGAAATAGACCGCGGGATCGATGGCGA






GGAAATCTAAATATATCAAGAATCAGAATTAGTTTAAGAAAAAAG






AAGAGGATTAATCTTGGTTTTCCCCTTGGT.






2. CVL44


The nucleic acid sequence for CVL44 is:











(SEQ ID NO: 62)



ACCAGGGGGAAAACGAAGTGGTGACTCAAATCATC







GAAGACCCTCGAGATTACATAGGTCCGGAACCTAT







GGCCTTCGTGACCGACCTCGAGTCAGAGTAGTTCA







ATAAGGACCTATCAAGTTTGGGCAATTTTTCGTCC







CCGACACAAAAATGTCATCCGTGCTTAAAGCATAT







GAGCGATTCACACTCACTCAAGAACTGCAAGATCA







GAGTGAGGAAGGTACAATCCCACCTACAACACTAA







AACCGGTAATCAGGGTATTTATACTAACCTCTAAT







AACCCAGAGCTAAGATCCCGGCTTCTTCTATTCTG







CCTACGGATTGTTCTCAGTAATGGTGCAAGGGATT







CCCATCGCTTTGGAGCATTACTTACAATGTTTTCG







CTACCATCAGCCACAATGCTCAATCATGTCAAATT







AGCTGACCAGTCACCAGAAGCTGATATCGAAAGGG







TAGAGATCGATGGCTTTGAGGAGGGATCATTCCGC







TTAATCCCCAATGCTCGTTCAGGTATGAGCCGTGG







AGAGATCAATGCCTATGCTGCACTTGCAGAAGATC







TACCTGACACACTAAACCATGCAACACCTTTTGTT







GATTCCGAAGTCGAGGGAACTGCATGGGATGAGAT







TGAGACTTTCTTAGATATGTGTTACAGTGTCCTAA







TGCAGGCATGGATAGTGACTTGCAAGTGCATGACT







GCGCCAGACCAACCTGCTGCTTCTATTGAGAAACG







CCTGCAAAAATATCGTCAGCAAGGCAGGATCAACC







CGAGATATCTCCTGCAACCGGAGGCTCGAAGAATA







ATCCAGAATGTAATCCGAAAGGGAATGGTGGTCAG







ACATTTCCTCACCTTTGAACTGCAGCTTGCCCGAG







CACAAAGCCTTGTATCAAATAGGTATTATGCTATG







GTAGGGGATGTTGGAAAGTATATAGAGAATTGTGG







AATGGGAGGCTTCTTTTTGACACTAAAATATGCAT







TAGGAACCAGATGGCCCACACTTGCTTTAGCTGCA







TTTTCAGGAGAGCTAACAAAGCTAAAGTCCCTCAT







GGCATTATACCAGACCCTTGGTGAGCAGGCCCGAT







ATTTGGCCCTATTGGAGTCACCACATTTGATGGAT







TTTGCTGCAGCAAACTACCCACTGCTATATAGCTA







TGCTATGGGAATAGGCTATGTGTTAGATGTCAACA







TGAGGAACTACGCTTTCTCCAGATCATACATGAAT







AAGACATATTTCCAATTGGGAATGGAAACTGCAAG







AAAACAACAGGGTGCAGTTGACATGAGGATGGCAG







AAGATCTCGGTCTAACTCAAGCCGAACGCACCGAG







ATGGCAAATACACTTGCCAAATTGACCACAGCAAA







TCGAGGGGCAGACACCAGGGGAGGAGTCAACCCGT







TCTCATCTATCACTGGGACAACTCAGGTGCCCGCT







GCAGCAACAGGTGACACATTCGAGAGTTACATGGC







AGCGGATCGACTGAGGCAGAGATATGCTGATGCAG







GCACCCACGATGATGAGATGCCACCATTGGAAGAG







GAGGAAGAGGACGACACATCTGCAGGTCCACGCAC







TGGACTAACTCTTGAACAAGTGGCCTTGGACATCC







AGAACGCAGCAGTTGGAGCTCCCATCCATACAGAT







GACCTGAATGCCGCACTGGGTGATCTTGACATCTA







GACAATTCAGATCCCAATCTTAAATCGACACACCT







AATTGACCAGTTAGATGGAACTACAGTGGATTCCA







TAAGGTTCCTGCCTACCATCGGCTTTTAAGAAAAA







AATAGGCCCGGACGGGTTAGCAACAAGCGACTGCC







GATGCCAATAACACAATCCACAATCTACAATGGAT







CCCACTGATCTGAGCTTCTCCCCAGATGAGATCAA







TAAGCTCATAGAGACAGGCCTGAATACTGTGGAGT







ATTTTACTTCCCAACAAGTCACAGGAACATCCTCT







CTTGGAAAGAATACAATACCACCAGGGGTCACAGG







ACTACTAACCAATGCTGCAGAGGCAAAGATCCAAG







AGTCAACCAACCATCAGAAGGGTTCAGTTGGTGGG







GGCGCAAAACCAAAGAAACCGCGACCAAAAATTGC







CATTGTGCCAGCAGATGACAAAACGGTGCCCGGAA







AGCCGATCCCAAACCCTCTATTAGGTCTGGACTCC







ACCCCGAGCACCCAAACTGTGCTTGATCTAAGTGG







GAAAACATTACCATCAGGATCCTATAAGGGGGTTA







AACTTGCGAAATTTGGAAAAGAAAATCTGATGACA







CGGTTCATCGAGGAACCCAGAGAGAATCCTATCGC







AACCAATTCCCCCATCGATTTTAAGAGGGGCAGGG







ATACCGGCGGGTTCCATAGAAGGGAGTACTCAATC







GGATGGGTGGGAGATGAAGTCAAGGTCACTGAGTG







GTGCAATCCATCCTGTTCTCCAATCACCGCTGCAG







CAAGGCGATTTGAATGCACTTGTCACCAGTGTCCA







GTCACTTGCTCTGAATGTGAACGAGATACTTAATA







CAGTGAGAAATTTGGACTCTCGGATGAATCAACTG







GAGACAAAAGTAGATCGCATTCTCTCATCTCAGTC







TCTAATCCAGACCATCAAGAATGACATAGTTGGAC







TTAAAGCAGGGATGGCTACTTTAGAAGGAATGATT







ACAACTGTGAAAATCATGGACCCGGGAGTTCCCAG







TAATGTTACTGTGGAAGATGTACGCAAGAAACTAA







GTAACCATGCTGTTGTTGTGCCAGAATCATTCAAT







GATAGTTTCTTGACTCAATCTGAAGATGTAATTTC







ACTTGATGAGTTGGCTCGACCAACTGCAACAAGTG







TTAAGAAGATTGTCAGGAAGGTTCCTCCTCAGAAG







GATCTGACTGGATTGAAGATCACACTAGAGCAATT







GGCAAAGGATTGCATCAGCAAACCGAAGATGAGGG







AAGAGTATCTCCTCAAAATCAACCAGGCTTCCAGT







GAGGCTCAGCTAATTGACCTCAAGAAAGCAATCAT







CCGCAGTGCAATTTGATCAAGAAACACCCAATTAC







ACTACACTGGTATGACACTGTACTAACCCTGAGGG







TTTTAGAAAAAACGATTAACGATAAATAAGCCCGA







ACACTACACACCACCCGAGGCAGCCATGCCATCCA







TCAGCATCCCCGCAGACCCCACCAATCCACGTCAA







TCAATAAAAGCGTTCCCAATTGTGATCAACCGTGA







TGGGGGTGAGAAAGGTCGCTTGGTTAAACAACTAC







GCACAACCTACTTGAATGACCTAGATACTCATGAG







CCACTGGTGACATTCGTAAATACTTATGGATTCAT







CTACGAACAGGATCGGGGAAATACCATTGTCGGAG







AGGATCAACATGGGAAGAAAAGAGAGGCTGTGACT







GCTGCAATGGTTACCCTTGGATGTGGGCCTAATCT







ACCATCATTAGGGAATGTCCTGGGACAACTGAGTG







AATTCCAGGTCATTGTTAGGAAGACATCCAGCAAA







GCGGAAGAGATGGTCTTTGAAATTGTTAAGTATCC







GAGAATATTTCGGGGTCATACATTAATCCAGAAAG







GACTAGTCTGTGTCTCCGCAGAAAAATTTGTTAAG







TCACCAGGGAAAGTACAATCTGGAATGGACTATCT







CTTCATTCCGACATTTCTGTCAGTGACTTACTGTC







CAGCTGCAATCAAATTTCAGGTACCTGGCCCCATG







TTGAAAATGAGATCAAGATACACTCAGAGCTTACA







ACTTGAACTAATGATAAGAATCCTGTGTAAGCCCG







ATTCGCCACTTATGAAGGTCCATATCCCTGACAAG







GAAGGAAGAGGATGTCTTGTATCAGTATGGTTGCA







TGTATGCAATATCTTCAAATCAGGAAACAAGAATG







GCAGTGAGTGGCAGGAATACTGGATGAGAAAGTGT







GCTAACATGCAACTTGAAGTGTCGATTGCAGATAT







GTGGGGACCAACTATCATAATTCATGCCAGAGGTC







ACATTCCCAAAAGTGCTAAGTTGTTTTTTGGAAAG







GGTGGATGGAGCTGCCATCCACTTCACGAAGTTGT







TCCAAGTGTCACTAAAACACTATGGTCCGTGGGCT







GTGAGATTACAAAGGCGAAGGCAATAATACAAGAG







AGTAGCATCTCTCTTCTCGTGGAGACTACTGACAT







CATAAGTCCAAAAGTCAAAATTTCATCTAAGCATC







GCCGCTTTGGGAAATCAAATTGGGGTCTGTTCAAG







AAAACCAAATCACTGCCCAACCTGACGGAGCTGGA







ATGACTGACCCCCAATCGAGACTACACCACCTCAA







ACTATAGGTGGGTGGTACCTCAGTGATTAATCTCG







TAAGCACTGATCGTAGGCTACAACACACTAATATT







ATCCAGATTAGAGAGCTTAATTAGCTCTGTATTAA







TAATAACACTACTATTCCAATAACTGGAATCACCA







GCTTGATTTATCTCCAAAATGATTCAAAGAAAACA







AATCATATTAAGACTATCCTAAGCACGAACCCATA







TCGTCCTTCAAATCATGGGTACTATAATTCAATTT







CTGGTGGTCTCCTGTCTATTGGCAGGAGCAGGCAG







TCTTGATCCAGCAGCCCTCATGCAAATCGGTGTCA







TTCCAACAAATGTCCGGCAACTTATGTATTATACT







GAGGCCTCATCAGCATTCATTGTTGTGAAGTTAAT







GCCTACAATTGACTCGCCGATTAGTGGATGTAATA







TAACATCAATTTCAAGCTATAATGCAACAGTGACA







AAACTCCTACAGCCGATCGGTGAGAATTTGGAGAC







GATTAGGAACCAGTTGATTCCAACTCGGAGGAGAC







GCCGGTTTGCAGGGGTGGTGATTGGATTAGCTGCA







TTAGGAGTAGCTACTGCCGCACAGGTCACTGCCGC







AGTAGCACTAGTAAAGGCAAATGAAAATGCTGCGG







CTATACTCAATCTCAAAAATGCAATCCAAAAAACA







AATGCAGCAGTTGCAGATGTGGTCCAGGCCACACA







ATCACTAGGAACaGCAGTTCAAGCAGTTCAAGATC







ACATAAACAGTGTGGTAAGTCCAGCAATTACAGCA







GCCAATTGTAAAGCCCAAGATGCTATCATTGGCTC







AATCCTCAATCTCTATTTGACCGAGTTGACAACTA







TCTTCCACAATCAAATTACAAACCCTGCATTGAGT







CCTATTACAATTCAAGCTTTAAGGATCCTACTAGG







GAGTACCTTGCCGACTGTGGTCGAAAAATCTTTCA







ATACCCAGATAAGTGCGGCTGAGCTTCTCTCATCA







GGGTTATTGACAGGCCAGATTGTGGGATTAGATTT







GACCTATATGCAGATGGTCATAAAAATTGAGCTGC







CAACTTTAACTGTACAACCTGCAACCCAGATCATA







GATCTGGCCACCATTTCTGCATTCATTAACAATCA







AGAAGTCATGGCCCAATTACCAACACGTGTTATTG







TGACTGGCAGCTTGATCCAAGCCTATCCCGCATCG







CAATGCACTATTACACCCAACACTGTGTACTGTAG







GTATAATGATGCCCAAGTACTCTCAGATGATACGA







TGGCTTGCCTCCAAGGTAACTTGACAAGATGCACC







TTCTCTCCAGTGGTTGGGAGCTTTCTCACTCGATT







CGTGCTGTTCGATGGAATAGTTTATGCAAATTGCA







GGTCGATGTTGTGCAAGTGCATGCAGCCTGCTGCT







GTGATCCTACAGCCGAGTTCATCCCCTGTAACTGT







CATTGACATGTACAAATGTGTGAGTCTGCAGCTTG







ACAATCTCAGATTCACCATCACTCAATTGGCCAAT







GTAACCTACAATAGCACCATCAAGCTTGAAACATC







CCAGATCTTGCCTATTGATCCGTTGGATATATCCC







AGAATCTAGCTGCGGTGAATAAGAGTCTAAGTGAT







GCACTACAACACTTAGCACAAAGTGACACATACCT







TTCTGCAATCACATCAGCTACGACTACAAGTGTAT







TATCCATAATAGCAATCTGTCTTGGATCGTTAGGT







TTAATATTAATAATCTTGCTCAGTGTAGTTGTGTG







GAAGTTATTGACCATTGTCGCTGCTAATCGAAATA







GAATGGAGAATTTTGTTTATCATAATTCAGCATTC







CACCACTCACGATCTGATCTCAGTGAGAAAAATCA







ACCTGCAACTCTTGGAACAAGATAAGACAGTCATC







CATTAGTAATTTTTAAGAAAAAAACGATAGGACCG







AAACTAGTATTGAAAGAACCGTCTCGGTCAATCTA







GGTAATCGAGCTGcTACCGTCTCGGAAAGCTCAAA







TCATGCTGCCTGATCCGGAAGATCCGGAAAGCAAA







AAAGCTACAAGGAGAACAGGAAACCTAATTATCTG







CTTCCTATTCATCTTCTTTCCGTTTGTAAACTTCA







TTGTTCCAACTCTAAGACACTTGCTGTCCTAACAC







CTGCTATAGGCTATCCACTGCATCATCTCTTTTTA







AGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGC







GACTGCCGGTGCCAACAACACAATCCACAATCTAC







AGTCGACGCGGCCGCCACCatgttcgtgttcctgg







tgctgctgccactggtcagcagccagtgcgtgaat







ttcactacccggacccagctgcctcctgcttatac







aaacagcttcaccaggggagtgtactaccccgata







aggtgttccgcagctctgtgctgcacagcacccag







gacttgtttcttcccttcttcagcaacgtgacctg







gttccacgccatccacgtgtccggcaccaacggca







ccaaaagattcgccaatcctgtgctgcctttcaac







gatggcgtgtactttgcctctacagagaagtctaa







catcatcagaggctggatcttcggcacaaccctgg







attctaaaacccagagcctgctgatcgtgaacaat







gccaccaatgtagtgatcaaggtttgtgagttcca







gttctgcaacgacccctttctgggcgtttactacc







acaagaacaacaaaagctggatggaaagcgagttc







agggtgtactctagcgccaacaactgtaccttcga







gtacgtgagccagccttttctgatggacctggagg







gcaagcagggcaacttcaaaaacctgcgggagttc







gtgtttaagaacatcgacggatacttcaagattta







ctccaagcacaccccaattaacttggttagaggac







tgccccaaggcttcagcgccctggaacccctggtg







gacctgcctatcggcatcaacatcacaagattcca







aaccctgcatagaagctatctgacaccaggcgact







ctagctctggatggacagccggcgccgctgcttat







tacgtgggctacctgcagcctagaaccttcctcct







gaaatacaacgagaacggaaccatcaccgacgccg







tggactgcgccctggatcctctgagcgagacaaag







tgcaccctgaagtccttcaccgtcgaaaagggcat







ctaccaaacaagcaacttcagagtgcagcctactg







agagcatcgtgcggtttccaaacatcaccaacctg







tgtccttttggcgaggtgttcaacgccacccggtt







cgcttccgtgtacgcctggaatagaaagcggatca







gcaactgcgtggccgactacagcgtgctgtataat







agcgcctcattttctacttttaaatgttacggcgt







gtctcctacaaagctgaacgatctgtgcttcacaa







atgtgtacgccgatagcttcgtgattagaggcgac







gaggtgcggcagatcgcccctggccagaccggcaa







catcgctgactacaactacaagctgcctgacgact







tcaccggctgtgtgatcgcatggaacagcaataac







ctggactctaaggtgggcggaaactacaattacct







gtacagactgttcagaaagagcaacctgaagccct







tcgagagagatatctccacagaaatctatcaggcc







ggatctacaccttgtaatggcgtgaagggcttcaa







ctgctacttccctctgcaatcctacggctttcagc







ccacatacggcgtgggctaccagccataccgggtc







gtggtgctgagcttcgagctgctgcacgcccctgc







cacagtgtgcggccctaagaagagcaccaatctgg







taaagaacaagtgcgtcaacttcaatttcaacggc







ctgaccgggaccggagtgctgaccgaaagcaacaa







gaaattcctgccgttccagcagttcggcagagata







tcgccgacaccaccgatgccgtgcgggacccccag







acacttgaaatcctggacatcaccccttgcagttt







tggcggcgtgtccgtgatcacacctggaacaaaca







ccagcaaccaggtggccgtgctgtaccagggcgtc







aactgcaccgaggtccccgtggccatccacgccga







tcagctgacacctacatggcgggtgtactctaccg







gcagcaacgtgttccaaaccagagccggctgcctg







atcggcgctgagcacgtgaacaacagctacgagtg







cgacattcctatcggtgctggcatctgcgcctctt







accagacacagacaaacagccccagaagagcgaga







agcgtggctagtcagagcatcatcgcctacaccat







gagcctgggcgtggagaacagcgtggcctactcta







acaatagcatcgccatcccaaccaacttcacaatc







tctgtgaccacagagatcctgcccgtgtccatgac







caagacatctgtggactgcacaatgtatatctgtg







gcgattctaccgagtgcagcaacctgctgctccag







tacggcagcttttgtacccagctgaatagagccct







gacaggcatcgccgtggagcaggataagaacacac







aggaggtgttcgcccaggtgaagcaaatctacaag







accccccctatcaaggactttggcggcttcaattt







ttcccagatcctgcctgatccatccaagccttcta







agcggagctttatcgaggacctgctgttcaacaag







gtgaccctggccgatgccggcttcatcaagcagta







tggcgattgcctgggcgacatcgcagccagggacc







tgatctgcgcccagaagtttaatggcctgaccgtg







ctgccacccctgctgacagatgagatgatcgcaca







gtacacaagcgccctgctggccggcaccatcacat







ccggatggaccttcggcgcaggagccgccctccag







atcccctttgccatgcagatggcctataggttcaa







cggcatcggcgtgacccagaatgtgctgtacgaga







accagaagctgatcgccaatcagtttaactccgcc







atcggcaagatccaggacagcctgtcctctacagc







cagcgccctgggcaagctccaggatgtggtgaatc







agaacgcccaggccctgaataccctggtgaagcag







ctgagcagcaacttcggcgccatctctagcgtgct







gaatgacatcctgagccggctggacaaggtggagg







cagaggtgcagatcgaccggctgatcaccggccgg







ctccagagcctccagacctatgtgacacagcagct







gatcagggccgccgagatcagggccagcgccaatc







tggcagcaaccaagatgtccgagtgcgtgctgggc







cagtctaagagagtggacttttgtggcaagggcta







tcacctgatgtccttccctcagtctgccccacacg







gcgtggtgtttctgcacgtgacctacgtgcccgcc







caggagaagaacttcaccacagcccctgccatctg







ccacgatggcaaggcccactttccaagggagggcg







tgttcgtgtccaacggcacccactggtttgtgaca







cagcgcaatttctacgagccccagatcatcaccac







agacaacaccttcgtgagcggcaactgtgacgtgg







tcatcggcatcgtgaacaataccgtgtatgatcca







ctccagcccgagctggacagctttaaggaggagct







ggataagtatttcaagaatcacacctcccctgacg







tggatctgggcgacatcagcggcatcaatgcctcc







gtggtgaacatccagaaggagatcgaccgcctgaa







cgaggtggctaagaatctgaacgagagcctgatcg







acctccaggagctgggcaagtatgagcagtacatc







aagtggccctggtacatctggctgggcttcatcgc







cggcctgatcgccatcgtgatggtgaccatcatgc







tgtgctgtatgacatcctgctgttcttgcctgaag







ggctgctgtagctgtggctcctgctgtAAGTTATT







GACCATTGTCGTTGCTAATCGAAATAGAATGGAGA







ATTTTGTTTATCATAAATGAACGCGTGCTAGCCTC







CTGCCATACTTCCTACTCACATCATATCTATTTTA







AAGAAAAAATAGGCCCGAACACTAATCGTGCCGGC







AGTGCCACTGCACACACAACACTACACATACAATA







CACTACAATGGTTGCAGAAGATGCCCCTGTTAGGG







GCACTTGCCGAGTATTATTTCGAACAACAACTTTA







ATTTTTCTATGCACACTATTAGCATTAAGCATCTC







TATCCTTTATGAGAGTTTAATAACCCAAAAGCAAA







TCATGAGCCAAGCAGGCTCAACTGGATCTAATTCT







AGATTAGGAAGTATCACTGATCTTCTTAATAATAT







TCTCTCTGTCGCAAATCAGATTATATATAACTCTG







CAGTCGCTCTACCTCTACAATTGGACACTCTTGAA







TCAACACTCCTTACAGCCATTAAGTCTCTTCAAAC







AAGTGACAAGCTAGAACAGAACTGCTCGTGGGGTG







CTGCACTGATTAATGATAATAGATACATTAATGGC







ATCAATCAGTTCTATTTCTCAATTGCTGAGGGTCG







CAAGCTGACACTTGGCCCACTTCTTAATATACCTA







GTTTCATTCCAACTGCCACGACACCAGAGGGCTGC







ACCAGGATCCCATCATTCTCGCTCACCAAGACACA







CTGGTGTTATACACACAATGTTATCCTGAATGGAT







GCCAGGATCATGTATCCTCAAATCAATTTGTTTCC







ATGGGAATCATTGAACCCACTTCTGCCGGGTTTCC







ATCCTTTCGAACCCTAAAGACTCTATATCTCAGCG







ATGGGGTCAATCGTAAGAGCTGCTCTATCAGTACA







GTTCCGGGGGGTTGTATGATGTACTGTTTCGTCTC







TACTCAACCAGAGAGGGATGACTACTTTTCTACCG







CTCCTCCAGAACAACGAATTATTATAATGTACTAT







AATGATACAATCGTGGAGCGCATAATTAATCCACC







CGGGGTACTAGATGTATGGGCAACATTGAACCCAG







GAACAGGAAGCGGGGTATATTATTTAGGTTGGGTA







CTCTTTCCAATATATGGCGGCGTGATTAAAGATAC







GAGTTTATGGAATAATCAAGCAAATAAATACTTTA







TCCCCCAGATGGTTGCTGCTCTCTGCTCACAAAAC







CAGGCAACTCAAGTCCAAAATGCTAAGTCATCATA







CTATAGCAGCTGGTTTGGCAATCGAATGATTCAGT







CTGGGATCCTGGCATGTCCTCTTCAACAGGATCTA







ACCAATGAGTGTTTAGTTCTGCCCTTTTCTAATGA







TCAGGTGCTTATGGGTGCTGAAGGGAGATTATACA







TGTATGGTGACTCGGTGTATTACTACCAAAGAAGC







AATAGTTGGTGGCCTATGACCATGCTGTATAAGGT







AACCATAACATTCACTAATGGTCAGCCATCTGCTA







TATCAGCTCAGAATGTGCCCACACAGCAGGTCCCT







AGACCTGGGACAGGAAGCTGCTCTGCAACAAATAG







ATGTCCCGGTTTTTGCTTGAAAGGAGTGTATGCTG







ATGCCTGGTTACTGACCAACCCTTCGTCTACCAGT







ACATTTGGATCAGAAGCAACCTTCACTGGTTCTTA







TCTCAACGCAGCAACTCAGCGTATCAATCCGACGA







TGTATATCGCGAACAACACACAGATCATAAGCTCA







CAGCAATTTGGATCAAGCGGTCAAGAAGCAGCATA







TGGCCACACAACTTGTTTTAGGGACACAGGCTCTG







TTATGGTATACTGTATCTATATTATTGAATTGTCC







TCATCTCTCTTAGGACAATTTCAGATTGTCCCATT







TATCCGTCAGGTGACACTATCCTAAAGGCAGAAGC







CTCCAGGTCTGACCCAGCCAATCAAAGCATTATAC







CAGACCATGGAATGCATACCAAACATTATTGACAC







TAATGACACACAAAATTGGTTTTAAGAAAAACCAA







GAGAACAATAGGCCAGAATGGCTGGGTCTCGGGAG







ATATTACTCCCTGAAGTCCATCTCAATTCACCAAT







TGTAAAGCATAAGCTATACTATTACATTCTACTTG







GAAACCTCCCAAATGAGATCGACATTGACGATTTA







GGTCCATTACATAATCAAAATTGGAATCAAATAGC







ACATGAAGAGTCTAACTTAGCCCAACGCTTGGTAA







ATGTAAGAAATTTTCTAATTACCCACATCCCTGAT







CTTAGAAAGGGCCATTGGCAAGAGTATGTCAATGT







AATACTGTGGCCGCGAATTCTTCCCTTGATCCCGG







ATTTTAAAATCAATGACCAATTGCCTCTACTCAAA







AATTGGGACAAGTTAGTTAAAGAATCATGTTCAGT







AATCAATGCGGGTACTTCCCAGTGCATTCAGAATC







TCAGCTATGGACTGACAGGTCGTGGGAACCTCTTT







ACACGATCACGTGAACTCTCTGGTGACCGCAGGGA







TATTGATCTTAAGACGGTTGTGGCAGCATGGCATG







ACTCAGACTGGAAAAGAATAAGTGATTTTTGGATT







ATGATCAAATTCCAGATGAGACAATTAATTGTTAG







GCAAACAGATCATAATGATCCTGATTTAATCACGT







ATATCGAAAATAGAGAAGGCATAATCATCATAACC







CCTGAACTGGTAGCATTATTTAACACTGAGAATCA







TACACTAACATACATGACCTTTGAAATTGTACTGA







TGGTTTCAGATATGTACGAAGGTCGTCACAACATT







TTATCACTATGCACAGTTAGCACTTACCTGAATCC







TCTGAAGAAAAGAATAACATATTTATTGAGCCTTG







TAGATAACTTAGCTTTTCAGATAGGTGATGCTGTA







TATAACATAATTGCTTTGCTAGAATCCTTTGTATA







TGCACAGTTGCAAATGTCAGATCCCATCCCAGAAC







TCAGAGGACAATTCCATGCATTCGTATGTTCTGAG







ATTCTTGATGCACTAAGGGGAACTAATAGTTTCAC







CCAGGATGAATCAAGAACTGTGACAACCAATTTGA







TATCCCCATTCCAAGATCTGACCCCAGATCTTACG







GCTGAATTGCTCTGTATAATGAGGCTTTGGGGACA







CCCCATGCTCACCGCCAGTCAAGCTGCGGGAAAGG







TACGCGAGTCCATGTGTGCTGGAAAAGTATTAGAC







TTTCCCACCATTATGAAAACACTAGCCTTTTTCCA







TACTATTCTGATCAATGGATACAGGAGGAAGCATC







ATGGAGTATGGCCACCCTTAAACTTACCGGGTAAT







GCTTCAAAGGGTCTCACGGAACTTATGAATGACAA







TACTGAGATAAGCTATGAATTCACACTTAAGCATT







GGAAGGAAATCTCTCTTATAAAATTCAAGAAATGT







TTTGATGCAGACGCAGGTGAGGAACTCAGTATATT







TATGAAAGATAAAGCAATTAGTGCCCCAAAACAAG







ATTGGATGAGTGTGTTTAGAAGAAGCCTAATCAAA







CAGCGCCATCAGCATCATCAGGTCCCCCTACCAAA







TCCATTCAATCGACGGCTATTGCTAAACTTTCTCG







GAGATGACAAATTCGACCCGAATGTGGAGCTACAG







TATGTAACATCAGGTGAGTATCTACATGATGACAC







GTTTTGTGCATCATATTCACTAAAAGAGAAGGAAA







TTAAACCTGATGGTCGAATTTTTGCAAAGTTGACT







AAGAGAATGAGATCATGTCAAGTTATAGCAGAATC







TCTTTTAGCGAACCATGCTGGGAAGTTAATGAAAG







AGAATGGTGTTGTGATGAATCAGCTATCATTAACA







AAATCACTATTAACAATGAGTCAGATTGGAATAAT







ATCCGAGAAAGCTAGAAAATCGACTCGAGATAACA







TAAATCAACCTGGTTTCCAGAATATCCAGAGAAAT







AAATCACATCACTCCAAGCAAGTCAATCAGCGAGA







TCCAAGTGATGACTTTGAATTGGCAGCATCTTTTT







TAACTACTGATCTCAAAAAATATTGTTTACAATGG







AGGTACCAGACAATTATCCCATTTGCTCAATCATT







AAACAGAATGTATGGTTATCCTCATCTCTTTGAGT







GGATTCACTTACGGCTAATGCGTAGTACACTTTAC







GTGGGGGATCCCTTCAACCCACCAGCAGATACCAG







TCAATTTGATCTAGATAAAGTAATTAATGGAGATA







TCTTCATTGTATCACCCAGAGGTGGAATTGAAGGG







CTATGTCAAAAGGCTTGGACAATGATATCTATCTC







TGTGATAATTCTATCTGCCACAGAGTCTGGCACAC







GAGTAATGAGTATGGTGCAGGGAGATAATCAAGCA







ATTGCTGTCACCACACGAGTACCAAGGAGCCTGCC







GACTCTTGAGAAAAAGACTATTGCTTTTAGATCTT







GTAATCTATTCTTTGAGAGGTTAAAATGTAATAAT







TTTGGATTAGGTCACCATTTGAAAGAACAAGAGAC







TATCATTAGTTCTCACTTCTTTGTTTATAGCAAGA







GAATATTCTATCAGGGGAGGATTCTAACGCAAGCC







TTAAAAAATGCTAGTAAGCTCTGCTTGACAGCTGA







TGTCCTAGGAGAATGTACCCAATCATCATGTTCTA







ATCTTGCAACTACTGTCATGAGGTTAACTGAGAAT







GGTGTTGAAAAAGATATCTGTTTCTACTTGAATAT







CTATATGACCATCAAACAGCTCTCCTATGATATCA







TCTTCCCTCAAGTGTCAATTCCTGGAGATCAGATC







ACATTAGAATACATAAATAATCCACACCTGGTATC







ACGATTGGCTCTTCTGCCATCCCAGCTAGGAGGTC







TAAACTACCTGTCATGCAGTAGGCTGTTCAATCGA







AACATAGGCGACCCGGTGGTTTCCGCAGTTGCAGA







TCTTAAGAGATTAATTAAATCAGGATGTATGGATT







ACTGGATCCTTTATAACTTATTAGGGAGAAAACCG







GGAAACGGCTCATGGGCTACTTTAGCAGCTGACCC







GTACTCAATCAATATAGAGTATCAATACCCCCCAA







CTACAGCTCTTAAGAGGCACACCCAACAAGCTCTG







ATGGAACTCAGTACGAATCCAATGTTACGTGGCAT







ATTCTCTGACAATGCACAGGCAGAAGAAAATAATC







TTGCTAGATTTCTCCTGGATAGGGAGGTGATCTTT







CCGCGTGTAGCTCACATCATCATTGAGCAAACCAG







TGTCGGGAGGAGAAAACAGATTCAAGGATATTTGG







ATTCAACTAGATCGATAATGAGTAAATCACTAGAA







ATTAAGCCCTTGTCCAATAGGAAGCTTAATGAAAT







ACTGGATTACAACATCAATTACCTAGCTTACAATT







TGGCATTACTCAAGAATGCTATTGAACCTCCGACT







TATTTGAAAGCAATGACTCTTGAAACATGTAGCAT







CGACATTGCAAGGAGCCTCCGGAAGCTCTCCTGGG







CCCCACTCTTGGGTGGGAGAAATCTTGAAGGATTA







GAGACGCCAGATCCCATTGAAATTACTGCAGGAGC







ATTAATTGTTGGATCGGGCTACTGTGAACAGTGTG







CTGCAGGAGACAATCGATTCACATGGTTTTTCTTG







CCATCTGGTATCGAGATAGGAGGGGATCCCCGTGA







TAATCCTCCTATCCGTGTACCGTACATTGGCTCCA







GGACTGATGAGAGGAGGGTAGCCTCAATGGCATAC







ATCAGGGGTGCCTCGAGTAGCCTAAAAGCAGTTCT







TAGACTGGCGGGAGTGTACATCTGGGCATTCGGAG







ATACTCTGGAGAATTGGATAGATGCACTGGATTTG







TCTCACACTAGAGTTAACATCACACTTGAACAGCT







GCAATCCCTCACCCCACTTCCAACCTCTGCCAATC







TAACCCATCGGTTGGATGATGGCACAACTACCCTA







AAGTTTACTCCTGCGAGCTCTTACACCTTTTCAAG







TTTCACTCATATATCAAATGATGAGCAATACCTGA







CAATTAATGACAAAACTGCAGATTCAAATATAATC







TACCAACAGTTAATGATCACTGGACTCGGAATTTT







AGAAACATGGAATAATCCCCCAATCAATAGAACAT







TCGAAGAATCTACCCTACATTTGCACACTGGTGCA







TCATGTTGTGTCCGACCTGTGGACTCCTGCATCAT







CTCAGAAGCATTAACAGTCAAGCCACATATTACAG







TACCGTACAGCAATAAATTTGTATTTGATGAAGAC







CCGCTATCTGAATATGAGACTGCAAAACTGGAATC







GTTATCATTTCAAGCCCAATTAGGCAACATTGATG







CTGTAGATATGACAGGTAAATTAACATTATTGTCC







CAATTCACTGCAAGGCAGATTATTAATGCAATCAC







TGGACTCGATGAGTCTGTCTCTCTTACTAATGATG







CCATTGTTGCATCAGACTATGTCTCCAATTGGATT







AGTGAATGCATGTATACCAAATTAGATGAATTATT







TATGTATTGTGGGTGGGAACTACTATTGGAACTAT







CCTATCAAATGTATTATCTGAGGGTAGTTGGGTGG







AGTAATATAGTGGATTATTCTTACATGATCTTGAG







AAGAATCCCGGGTGCAGCATTAAACAATCTGGCAT







CTACATTAAGTCATCCAAAACTTTTCCGACGAGCT







ATCAACCTAGATATAGTTGCCCCCTTAAATGCTCC







TCATTTTGCATCTCTGGACTACATCAAGATGAGTG







TGGATGCAATACTCTGGGGCTGTAAAAGAGTCATC







AATGTGCTCTCCAATGGAGGGGACTTAGAATTAGT







TGTGACATCTGAAGATAGCCTTATTCTCAGTGACC







GATCCATGAATCTCATTGCAAGGAAATTAACTTTA







TTATCACTGATTCACCATAATGGTTTGGAACTACC







AAAGATTAAGGGGTTCTCTCCTGATGAGAAGTGTT







TCGCTTTGACAGAATTTTTGAGGAAAGTGGTGAAC







TCAGGGTTGAGTTCAATAGAGAACCTATCAAATTT







TATGTACAATGTGGAGAACCCACGGCTTGCAGCAT







TCGCCAGCAACAATTACTACCTGACCAGAAAATTA







TTGAATTCAATACGAGATACTGAGTCGGGTCAAGT







AGCAGTCACCTCATATTATGAATCATTAGAATATA







TTGATAGTCTTAAGCTAACCCCACATGTGCCTGGT







ACCTCATGCATTGAGGATGATAGTCTATGTACAAA







TGATTACATAATCTGGATCATAGAGTCTAATGCAA







ACTTGGAGAAGTATCCAATTCCAAATAGCCCTGAG







GATGATTCCAATTTCCATAACTTTAAGTTGAATGC







TCCATCGCACCATACCTTACGCCCATTAGGGTTGT







CATCAACTGCTTGGTATAAGGGTATAAGCTGTTGC







AGGTACCTTGAGCGATTAAAGCTACCACAAGGTGA







TCATTTATATATTGCAGAAGGTAGTGGTGCCAGTA







TGACAATCATAGAATACCTATTCCCAGGAAGAAAG







ATATATTACAATTCTTTATTTAGTAGTGGTGACAA







TCCCCCACAAAGAAATTATGCACCAATGCCTACTC







AGTTCATTGAGAGTGTCCCATACAAGCTCTGGCAA







GCACACACAGATCAATATCCCGAGATTTTTGAGGA







CTTCATCCCTCTATGGAACGGAAATGCCGCCATGA







CTGACATAGGAATGACAGCTTGTGTAGAATTCATC







ATCAATCGAGTCGGCCCAAGGACTTGCAGTTTAGT







ACATGTAGATTTGGAATCAAGTGCAAGCTTAAATC







AACAATGCCTGTCAAAGCCGATAATTAATGCTATC







ATCACTGCTACATGATCACTTTCTTATGGTGCTAC







TTTGAGAGAATCACTGTTCTTAGGAGCACATATTC







TGGTCCAGCTAATCATGAGGTTTATTTAATTTGTA







TCCTTGCCAACAACTTTGCATTCCAGACTGTCTCG







CAGGCAACAGGAATGGCGATGACTTTAACCGATCA







AGGGTTTACTTTGATATCACCTGAAAGAATAAATC







AGTATTGGGATGGTCACTTGAAGCAAGAACGTATC







GTAGCAGAAGCAATTGATAAGGTGGTTCTAGGAGA







AGATGCTCTATTCAATTCGAGTGATAATGAATTAA







TTCTCAAATGTGGAGGGACACCAAATGCACGGAAT







CTTATCGATATCGAGCCAGTCGCAACTTTCATAGA







ATTTGAACAACTGATCTGCACAATGTTGACAACCC







ACTTGAAGGAAATAATTGATATAACAAGGTCTGGA







ACCCAGGATTATGAAAGTTTATTACTCACTCCTTA







CAATTTAGGTCTTCTTGGTAAAATCAGTACGATAG







TGAGATTATTAACAGAAAGGATTCTAAATCATACT







ATCAGGAATTGGTTGATCCTCCCACCTTCGCTCCG







GATGATCGTGAAGCAGGACTTGGAATTCGGCATAT







TCAGGATTACTTCCATCCTCAATTCTGATCGGTTC







CTGAAGCTTTCTCCAAATAGGAAATACTTGATTAC







ACAATTAACTGCAGGCTACATTAGGAAATTGATTG







AGGGGGATTGTAATATCGATCTAACCAGACCTATC







CAAAAACAAATCTGGAAAGCATTAGGTTGTGTAGT







CTATTGTCACGATCCAGTAGATCAAAGGGAATCAA







CAGAGTTTATTGATATAAATATTAATGAAGAAATA







GACCGCGGGATCGATGGCGAGGAAATCTAAATATA







TCAAGAATCAGAATTAGTTTAAGAAAAAAGAAGAG







GATTAATCTTGGTTTTCCCCTTGGT.






3. CVL48


The nucleic acid sequence for CVL48 is:











(SEQ ID NO: 63)



ACCAGGGGGAAAACGAAGTGGTGACTCAAATCATC







GAAGACCCTCGAGATTACATAGGTCCGGAACCTAT







GGCCTTCGTGACCGACCTCGAGTCAGAGTAGTTCA







ATAAGGACCTATCAAGTTTGGGCAATTTTTCGTCC







CCGACACAAAAATGTCATCCGTGCTTAAAGCATAT







GAGCGATTCACACTCACTCAAGAACTGCAAGATCA







GAGTGAGGAAGGTACAATCCCACCTACAACACTAA







AACCGGTAATCAGGGTATTTATACTAACCTCTAAT







AACCCAGAGCTAAGATCCCGGCTTCTTCTATTCTG







CCTACGGATTGTTCTCAGTAATGGTGCAAGGGATT







CCCATCGCTTTGGAGCATTACTTACAATGTTTTCG







CTACCATCAGCCACAATGCTCAATCATGTCAAATT







AGCTGACCAGTCACCAGAAGCTGATATCGAAAGGG







TAGAGATCGATGGCTTTGAGGAGGGATCATTCCGC







TTAATCCCCAATGCTCGTTCAGGTATGAGCCGTGG







AGAGATCAATGCCTATGCTGCACTTGCAGAAGATC







TACCTGACACACTAAACCATGCAACACCTTTTGTT







GATTCCGAAGTCGAGGGAACTGCATGGGATGAGAT







TGAGACTTTCTTAGATATGTGTTACAGTGTCCTAA







TGCAGGCATGGATAGTGACTTGCAAGTGCATGACT







GCGCCAGACCAACCTGCTGCTTCTATTGAGAAACG







CCTGCAAAAATATCGTCAGCAAGGCAGGATCAACC







CGAGATATCTCCTGCAACCGGAGGCTCGAAGAATA







ATCCAGAATGTAATCCGAAAGGGAATGGTGGTCAG







ACATTTCCTCACCTTTGAACTGCAGCTTGCCCGAG







CACAAAGCCTTGTATCAAATAGGTATTATGCTATG







GTAGGGGATGTTGGAAAGTATATAGAGAATTGTGG







AATGGGAGGCTTCTTTTTGACACTAAAATATGCAT







TAGGAACCAGATGGCCCACACTTGCTTTAGCTGCA







TTTTCAGGAGAGCTAACAAAGCTAAAGTCCCTCAT







GGCATTATACCAGACCCTTGGTGAGCAGGCCCGAT







ATTTGGCCCTATTGGAGTCACCACATTTGATGGAT







TTTGCTGCAGCAAACTACCCACTGCTATATAGCTA







TGCTATGGGAATAGGCTATGTGTTAGATGTCAACA







TGAGGAACTACGCTTTCTCCAGATCATACATGAAT







AAGACATATTTCCAATTGGGAATGGAAACTGCAAG







AAAACAACAGGGTGCAGTTGACATGAGGATGGCAG







AAGATCTCGGTCTAACTCAAGCCGAACGCACCGAG







ATGGCAAATACACTTGCCAAATTGACCACAGCAAA







TCGAGGGGCAGACACCAGGGGAGGAGTCAACCCGT







TCTCATCTATCACTGGGACAACTCAGGTGCCCGCT







GCAGCAACAGGTGACACATTCGAGAGTTACATGGC







AGCGGATCGACTGAGGCAGAGATATGCTGATGCAG







GCACCCACGATGATGAGATGCCACCATTGGAAGAG







GAGGAAGAGGACGACACATCTGCAGGTCCACGCAC







TGGACTAACTCTTGAACAAGTGGCCTTGGACATCC







AGAACGCAGCAGTTGGAGCTCCCATCCATACAGAT







GACCTGAATGCCGCACTGGGTGATCTTGACATCTA







GACAATTCAGATCCCAATCTTAAATCGACACACCT







AATTGACCAGTTAGATGGAACTACAGTGGATTCCA







TAAGGTTCCTGCCTACCATCGGCTTTTAAGAAAAA







AATAGGCCCGGACGGGTTAGCAACAAGCGACTGCC







GATGCCAATAACACAATCCACAATCTACAATGGAT







CCCACTGATCTGAGCTTCTCCCCAGATGAGATCAA







TAAGCTCATAGAGACAGGCCTGAATACTGTGGAGT







ATTTTACTTCCCAACAAGTCACAGGAACATCCTCT







CTTGGAAAGAATACAATACCACCAGGGGTCACAGG







ACTACTAACCAATGCTGCAGAGGCAAAGATCCAAG







AGTCAACCAACCATCAGAAGGGTTCAGTTGGTGGG







GGCGCAAAACCAAAGAAACCGCGACCAAAAATTGC







CATTGTGCCAGCAGATGACAAAACGGTGCCCGGAA







AGCCGATCCCAAACCCTCTATTAGGTCTGGACTCC







ACCCCGAGCACCCAAACTGTGCTTGATCTAAGTGG







GAAAACATTACCATCAGGATCCTATAAGGGGGTTA







AACTTGCGAAATTTGGAAAAGAAAATCTGATGACA







CGGTTCATCGAGGAACCCAGAGAGAATCCTATCGC







AACCAATTCCCCCATCGATTTTAAGAGGGGCAGGG







ATACCGGCGGGTTCCATAGAAGGGAGTACTCAATC







GGATGGGTGGGAGATGAAGTCAAGGTCACTGAGTG







GTGCAATCCATCCTGTTCTCCAATCACCGCTGCAG







CAAGGCGATTTGAATGCACTTGTCACCAGTGTCCA







GTCACTTGCTCTGAATGTGAACGAGATACTTAATA







CAGTGAGAAATTTGGACTCTCGGATGAATCAACTG







GAGACAAAAGTAGATCGCATTCTCTCATCTCAGTC







TCTAATCCAGACCATCAAGAATGACATAGTTGGAC







TTAAAGCAGGGATGGCTACTTTAGAAGGAATGATT







ACAACTGTGAAAATCATGGACCCGGGAGTTCCCAG







TAATGTTACTGTGGAAGATGTACGCAAGAAACTAA







GTAACCATGCTGTTGTTGTGCCAGAATCATTCAAT







GATAGTTTCTTGACTCAATCTGAAGATGTAATTTC







ACTTGATGAGTTGGCTCGACCAACTGCAACAAGTG







TTAAGAAGATTGTCAGGAAGGTTCCTCCTCAGAAG







GATCTGACTGGATTGAAGATCACACTAGAGCAATT







GGCAAAGGATTGCATCAGCAAACCGAAGATGAGGG







AAGAGTATCTCCTCAAAATCAACCAGGCTTCCAGT







GAGGCTCAGCTAATTGACCTCAAGAAAGCAATCAT







CCGCAGTGCAATTTGATCAAGAAACACCCAATTAC







ACTACACTGGTATGACACTGTACTAACCCTGAGGG







TTTTAGAAAAAACGATTAACGATAAATAAGCCCGA







ACACTACACACCACCCGAGGCAGCCATGCCATCCA







TCAGCATCCCCGCAGACCCCACCAATCCACGTCAA







TCAATAAAAGCGTTCCCAATTGTGATCAACCGTGA







TGGGGGTGAGAAAGGTCGCTTGGTTAAACAACTAC







GCACAACCTACTTGAATGACCTAGATACTCATGAG







CCACTGGTGACATTCGTAAATACTTATGGATTCAT







CTACGAACAGGATCGGGGAAATACCATTGTCGGAG







AGGATCAACATGGGAAGAAAAGAGAGGCTGTGACT







GCTGCAATGGTTACCCTTGGATGTGGGCCTAATCT







ACCATCATTAGGGAATGTCCTGGGACAACTGAGTG







AATTCCAGGTCATTGTTAGGAAGACATCCAGCAAA







GCGGAAGAGATGGTCTTTGAAATTGTTAAGTATCC







GAGAATATTTCGGGGTCATACATTAATCCAGAAAG







GACTAGTCTGTGTCTCCGCAGAAAAATTTGTTAAG







TCACCAGGGAAAGTACAATCTGGAATGGACTATCT







CTTCATTCCGACATTTCTGTCAGTGACTTACTGTC







CAGCTGCAATCAAATTTCAGGTACCTGGCCCCATG







TTGAAAATGAGATCAAGATACACTCAGAGCTTACA







ACTTGAACTAATGATAAGAATCCTGTGTAAGCCCG







ATTCGCCACTTATGAAGGTCCATATCCCTGACAAG







GAAGGAAGAGGATGTCTTGTATCAGTATGGTTGCA







TGTATGCAATATCTTCAAATCAGGAAACAAGAATG







GCAGTGAGTGGCAGGAATACTGGATGAGAAAGTGT







GCTAACATGCAACTTGAAGTGTCGATTGCAGATAT







GTGGGGACCAACTATCATAATTCATGCCAGAGGTC







ACATTCCCAAAAGTGCTAAGTTGTTTTTTGGAAAG







GGTGGATGGAGCTGCCATCCACTTCACGAAGTTGT







TCCAAGTGTCACTAAAACACTATGGTCCGTGGGCT







GTGAGATTACAAAGGCGAAGGCAATAATACAAGAG







AGTAGCATCTCTCTTCTCGTGGAGACTACTGACAT







CATAAGTCCAAAAGTCAAAATTTCATCTAAGCATC







GCCGCTTTGGGAAATCAAATTGGGGTCTGTTCAAG







AAAACCAAATCACTGCCCAACCTGACGGAGCTGGA







ATGACTGACCCCCAATCGAGACTACACCACCTCAA







ACTATAGGTGGGTGGTACCTCAGTGATTAATCTCG







TAAGCACTGATCGTAGGCTACAACACACTAATATT







ATCCAGATTAGAGAGCTTAATTAGCTCTGTATTAA







TAATAACACTACTATTCCAATAACTGGAATCACCA







GCTTGATTTATCTCCAAAATGATTCAAAGAAAACA







AATCATATTAAGACTATCCTAAGCACGAACCCATA







TCGTCCTTCAAATCATGGGTACTATAATTCAATTT







CTGGTGGTCTCCTGTCTATTGGCAGGAGCAGGCAG







TCTTGATCCAGCAGCCCTCATGCAAATCGGTGTCA







TTCCAACAAATGTCCGGCAACTTATGTATTATACT







GAGGCCTCATCAGCATTCATTGTTGTGAAGTTAAT







GCCTACAATTGACTCGCCGATTAGTGGATGTAATA







TAACATCAATTTCAAGCTATAATGCAACAGTGACA







AAACTCCTACAGCCGATCGGTGAGAATTTGGAGAC







GATTAGGAACCAGTTGATTCCAACTCGGAGGAGAC







GCCGGTTTGCAGGGGTGGTGATTGGATTAGCTGCA







TTAGGAGTAGCTACTGCCGCACAGGTCACTGCCGC







AGTAGCACTAGTAAAGGCAAATGAAAATGCTGCGG







CTATACTCAATCTCAAAAATGCAATCCAAAAAACA







AATGCAGCAGTTGCAGATGTGGTCCAGGCCACACA







ATCACTAGGAACaGCAGTTCAAGCAGTTCAAGATC







ACATAAACAGTGTGGTAAGTCCAGCAATTACAGCA







GCCAATTGTAAAGCCCAAGATGCTATCATTGGCTC







AATCCTCAATCTCTATTTGACCGAGTTGACAACTA







TCTTCCACAATCAAATTACAAACCCTGCATTGAGT







CCTATTACAATTCAAGCTTTAAGGATCCTACTAGG







GAGTACCTTGCCGACTGTGGTCGAAAAATCTTTCA







ATACCCAGATAAGTGCGGCTGAGCTTCTCTCATCA







GGGTTATTGACAGGCCAGATTGTGGGATTAGATTT







GACCTATATGCAGATGGTCATAAAAATTGAGCTGC







CAACTTTAACTGTACAACCTGCAACCCAGATCATA







GATCTGGCCACCATTTCTGCATTCATTAACAATCA







AGAAGTCATGGCCCAATTACCAACACGTGTTATTG







TGACTGGCAGCTTGATCCAAGCCTATCCCGCATCG







CAATGCACTATTACACCCAACACTGTGTACTGTAG







GTATAATGATGCCCAAGTACTCTCAGATGATACGA







TGGCTTGCCTCCAAGGTAACTTGACAAGATGCACC







TTCTCTCCAGTGGTTGGGAGCTTTCTCACTCGATT







CGTGCTGTTCGATGGAATAGTTTATGCAAATTGCA







GGTCGATGTTGTGCAAGTGCATGCAGCCTGCTGCT







GTGATCCTACAGCCGAGTTCATCCCCTGTAACTGT







CATTGACATGTACAAATGTGTGAGTCTGCAGCTTG







ACAATCTCAGATTCACCATCACTCAATTGGCCAAT







GTAACCTACAATAGCACCATCAAGCTTGAAACATC







CCAGATCTTGCCTATTGATCCGTTGGATATATCCC







AGAATCTAGCTGCGGTGAATAAGAGTCTAAGTGAT







GCACTACAACACTTAGCACAAAGTGACACATACCT







TTCTGCAATCACATCAGCTACGACTACAAGTGTAT







TATCCATAATAGCAATCTGTCTTGGATCGTTAGGT







TTAATATTAATAATCTTGCTCAGTGTAGTTGTGTG







GAAGTTATTGACCATTGTCGCTGCTAATCGAAATA







GAATGGAGAATTTTGTTTATCATAATTCAGCATTC







CACCACTCACGATCTGATCTCAGTGAGAAAAATCA







ACCTGCAACTCTTGGAACAAGATAAGACAGTCATC







CATTAGTAATTTTTAAGAAAAAAACGATAGGACCG







AAACTAGTATTGAAAGAACCGTCTCGGTCAATCTA







GGTAATCGAGCTGcTACCGTCTCGGAAAGCTCAAA







TCATGCTGCCTGATCCGGAAGATCCGGAAAGCAAA







AAAGCTACAAGGAGAACAGGAAACCTAATTATCTG







CTTCCTATTCATCTTCTTTCCGTTTGTAAACTTCA







TTGTTCCAACTCTAAGACACTTGCTGTCCTAACAC







CTGCTATAGGCTATCCACTGCATCATCTCTTTTTA







AGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGC







GACTGCCGGTGCCAACAACACAATCCACAATCTAC







AGTCGACGCGGCCGCCACCatgttcgtcttcctgg







tcctgctgcctctggtctcctcacagtgcgtcaat







ctgacaactcggactcagctgccacctgcttatac







taatagcttcaccagaggcgtgtactatcctgaca







aggtgtttagaagctccgtgctgcactctacacag







gatctgtttctgccattctttagcaacgtgacctg







gttccacgccatcagcggcaccaatggcacaaagc







ggttcgacaatcccgtgctgccttttaacgatggc







gtgtacttcgcctctaccgagaagagcaacatcat







cagaggctggatctttggcaccacactggactcca







agacacagtctctgctgatcgtgaacaatgccacc







aacgtggtcatcaaggtgtgcgagttccagttttg







taatgatcccttcctgggcgtgtatcacaagaaca







ataagagctggatggagtccgagtttagagtgtat







tctagcgccaacaactgcacatttgagtacgtgag







ccagcctttcctgatggacctggagggcaagcagg







gcaatttcaagaacctgagggagttcgtgtttaag







aatatcgacggctacttcaaaatctactctaagca







cacccccatcaacctggtgcgcgacctgcctcagg







gcttcagcgccctggagcccctggtggatctgcct







atcggcatcaacatcacccggtttcagacactgct







ggccctgcacagaagctacctgacacccggcgact







cctctagcggatggaccgccggcgctgccgcctac







tatgtgggctacctccagccccggaccttcctgct







gaagtacaacgagaatggcaccatcacagacgcag







tggattgcgccctggaTcccctgagcgagacaaag







tgtacactgaagtcctttaccgtggagaagggcat







ctatcagacatccaatttcagggtgcagccaaccg







agtctatcgtgcgctttcctaatatcacaaacctg







tgcccatttggcgaggtgttcaacgcaacccgctt







cgccagcgtgtacgcctggaataggaagcggatca







gcaactgcgtggccgactatagcgtgctgtacaac







tccgcctctttcagcacctttaagtgctatggcgt







gtcccccacaaagctgaatgacctgtgctttacca







acgtctacgccgattctttcgtgatcaggggcgac







gaggtgcgccagatcgcccccggccagacaggcaa







gatcgcagactacaattataagctgccagacgatt







tcaccggctgcgtgatcgcctggaacagcaacaat







ctggattccaaagtgggcggcaactacaattatct







gtaccggctgtttagaaagagcaatctgaagccct







tcgagagggacatctctacagaaatctaccaggcc







ggcagcaccccttgcaatggcgtggagggctttaa







ctgttatttcccactccagtcctacggcttccagc







ccacaTATggcgtgggctatcagccttaccgcgtg







gtggtgctgagctttgagctgctgcacgccccagc







aacagtgtgcggccccaagaagtccaccaatctgg







tgaagaacaagtgcgtgaacttcaacttcaacggc







ctgaccggcacaggcgtgctgaccgagtccaacaa







gaagttcctgccatttcagcagttcggcagggaca







tcgATgataccacagacgccgtgcgcgacccacag







accctggagatcctggacatcacaccctgctcttt







cggcggcgtgagcgtgatcacacccggcaccaata







caagcaaccaggtggccgtgctgtatcaggGcgtg







aattgtaccgaggtgcccgtggctatccacgccga







tcagctgaccccaacatggcgggtgtacagcaccg







gctccaacgtcttccagacaagagccggatgcctg







atcggagcagagcacgtgaacaattcctatgagtg







cgacatcccaatcggcgccggcatctgtgcctctt







accagacccagacaaactctcAcagaagagcccgg







agcgtggcctcccagtctatcatcgcctataccat







gtccctgggcgccgagaacagcgtggcctactcta







acaatagcatcgccatcccaaTcaacttcacaatc







tctgtgaccacagagatcctgcccgtgtccatgac







caagacatctgtggactgcacaatgtatatctgtg







gcgattctaccgagtgcagcaacctgctgctccag







tacggcagcttttgtacccagctgaatagagccct







gacaggcatcgccgtggagcaggataagaacacac







aggaggtgttcgcccaggtgaagcaaatctacaag







accccccctatcaaggactttggcggcttcaattt







ttcccagatcctgcctgatccatccaagccttcta







agcggagctttatcgaggacctgctgttcaacaag







gtgaccctggccgatgccggcttcatcaagcagta







tggcgattgcctgggcgacatcgcagccagggacc







tgatctgcgcccagaagtttaatggcctgaccgtg







ctgccacccctgctgacagatgagatgatcgcaca







gtacacaagcgccctgctggccggcaccatcacat







ccggatggaccttcggcgcaggagccgccctccag







atcccctttgccatgcagatggcctataggttcaa







cggcatcggcgtgacccagaatgtgctgtacgaga







accagaagctgatcgccaatcagtttaactccgcc







atcggcaagatccaggacagcctgtcctctacagc







cagcgccctgggcaagctccaggatgtggtgaatc







agaacgcccaggccctgaataccctggtgaagcag







ctgagcagcaacttcggcgccatctctagcgtgct







gaatgacatcctggcTcggctggacaaggtggagg







cagaggtgcagatcgaccggctgatcaccggccgg







ctccagagcctccagacctatgtgacacagcagct







gatcagggccgccgagatcagggccagcgccaatc







tggcagcaaccaagatgtccgagtgcgtgctgggc







cagtctaagagagtggacttttgtggcaagggcta







tcacctgatgtccttccctcagtctgccccacacg







gcgtggtgtttctgcacgtgacctacgtgcccgcc







caggagaagaacttcaccacagcccctgccatctg







ccacgatggcaaggcccactttccaagggagggcg







tgttcgtgtccaacggcacccactggtttgtgaca







cagcgcaatttctacgagccccagatcatcaccac







aCacaacaccttcgtgagcggcaactgtgacgtgg







tcatcggcatcgtgaacaataccgtgtatgatcca







ctccagcccgagctggacagctttaaggaggagct







ggataagtatttcaagaatcacacctcccctgacg







tggatctgggcgacatcagcggcatcaatgcctcc







gtggtgaacatccagaaggagatcgaccgcctgaa







cgaggtggctaagaatctgaacgagagcctgatcg







acctccaggagctgggcaagtatgagcagtacatc







aagtggccctggtacatctggctgggcttcatcgc







cggcctgatcgccatcgtgatggtgaccatcatgc







tgtgctgtatgacatcctgctgttcttgcctgaag







ggctgctgtagctgtggctcctgctgtAAGTTATT







GACCATTGTCGTTGCTAATCGAAATAGAATGGAGA







ATTTTGTTTATCATAAATGAGCTAGCCTCCTGCCA







TACTTCCTACTCACATCATATCTATTTTAAAGAAA







AAATAGGCCCGAACACTAATCGTGCCGGCAGTGCC







ACTGCACACACAACACTACACATACAATACACTAC







AATGGTTGCAGAAGATGCCCCTGTTAGGGGCACTT







GCCGAGTATTATTTCGAACAACAACTTTAATTTTT







CTATGCACACTATTAGCATTAAGCATCTCTATCCT







TTATGAGAGTTTAATAACCCAAAAGCAAATCATGA







GCCAAGCAGGCTCAACTGGATCTAATTCTAGATTA







GGAAGTATCACTGATCTTCTTAATAATATTCTCTC







TGTCGCAAATCAGATTATATATAACTCTGCAGTCG







CTCTACCTCTACAATTGGACACTCTTGAATCAACA







CTCCTTACAGCCATTAAGTCTCTTCAAACAAGTGA







CAAGCTAGAACAGAACTGCTCGTGGGGTGCTGCAC







TGATTAATGATAATAGATACATTAATGGCATCAAT







CAGTTCTATTTCTCAATTGCTGAGGGTCGCAAGCT







GACACTTGGCCCACTTCTTAATATACCTAGTTTCA







TTCCAACTGCCACGACACCAGAGGGCTGCACCAGG







ATCCCATCATTCTCGCTCACCAAGACACACTGGTG







TTATACACACAATGTTATCCTGAATGGATGCCAGG







ATCATGTATCCTCAAATCAATTTGTTTCCATGGGA







ATCATTGAACCCACTTCTGCCGGGTTTCCATCCTT







TCGAACCCTAAAGACTCTATATCTCAGCGATGGGG







TCAATCGTAAGAGCTGCTCTATCAGTACAGTTCCG







GGGGGTTGTATGATGTACTGTTTCGTCTCTACTCA







ACCAGAGAGGGATGACTACTTTTCTACCGCTCCTC







CAGAACAACGAATTATTATAATGTACTATAATGAT







ACAATCGTGGAGCGCATAATTAATCCACCCGGGGT







ACTAGATGTATGGGCAACATTGAACCCAGGAACAG







GAAGCGGGGTATATTATTTAGGTTGGGTACTCTTT







CCAATATATGGCGGCGTGATTAAAGATACGAGTTT







ATGGAATAATCAAGCAAATAAATACTTTATCCCCC







AGATGGTTGCTGCTCTCTGCTCACAAAACCAGGCA







ACTCAAGTCCAAAATGCTAAGTCATCATACTATAG







CAGCTGGTTTGGCAATCGAATGATTCAGTCTGGGA







TCCTGGCATGTCCTCTTCAACAGGATCTAACCAAT







GAGTGTTTAGTTCTGCCCTTTTCTAATGATCAGGT







GCTTATGGGTGCTGAAGGGAGATTATACATGTATG







GTGACTCGGTGTATTACTACCAAAGAAGCAATAGT







TGGTGGCCTATGACCATGCTGTATAAGGTAACCAT







AACATTCACTAATGGTCAGCCATCTGCTATATCAG







CTCAGAATGTGCCCACACAGCAGGTCCCTAGACCT







GGGACAGGAAGCTGCTCTGCAACAAATAGATGTCC







CGGTTTTTGCTTGAAAGGAGTGTATGCTGATGCCT







GGTTACTGACCAACCCTTCGTCTACCAGTACATTT







GGATCAGAAGCAACCTTCACTGGTTCTTATCTCAA







CGCAGCAACTCAGCGTATCAATCCGACGATGTATA







TCGCGAACAACACACAGATCATAAGCTCACAGCAA







TTTGGATCAAGCGGTCAAGAAGCAGCATATGGCCA







CACAACTTGTTTTAGGGACACAGGCTCTGTTATGG







TATACTGTATCTATATTATTGAATTGTCCTCATCT







CTCTTAGGACAATTTCAGATTGTCCCATTTATCCG







TCAGGTGACACTATCCTAAAGGCAGAAGCCTCCAG







GTCTGACCCAGCCAATCAAAGCATTATACCAGACC







ATGGAATGCATACCAAACATTATTGACACTAATGA







CACACAAAATTGGTTTTAAGAAAAACCAAGAGAAC







AATAGGCCAGAATGGCTGGGTCTCGGGAGATATTA







CTCCCTGAAGTCCATCTCAATTCACCAATTGTAAA







GCATAAGCTATACTATTACATTCTACTTGGAAACC







TCCCAAATGAGATCGACATTGACGATTTAGGTCCA







TTACATAATCAAAATTGGAATCAAATAGCACATGA







AGAGTCTAACTTAGCCCAACGCTTGGTAAATGTAA







GAAATTTTCTAATTACCCACATCCCTGATCTTAGA







AAGGGCCATTGGCAAGAGTATGTCAATGTAATACT







GTGGCCGCGAATTCTTCCCTTGATCCCGGATTTTA







AAATCAATGACCAATTGCCTCTACTCAAAAATTGG







GACAAGTTAGTTAAAGAATCATGTTCAGTAATCAA







TGCGGGTACTTCCCAGTGCATTCAGAATCTCAGCT







ATGGACTGACAGGTCGTGGGAACCTCTTTACACGA







TCACGTGAACTCTCTGGTGACCGCAGGGATATTGA







TCTTAAGACGGTTGTGGCAGCATGGCATGACTCAG







ACTGGAAAAGAATAAGTGATTTTTGGATTATGATC







AAATTCCAGATGAGACAATTAATTGTTAGGCAAAC







AGATCATAATGATCCTGATTTAATCACGTATATCG







AAAATAGAGAAGGCATAATCATCATAACCCCTGAA







CTGGTAGCATTATTTAACACTGAGAATCATACACT







AACATACATGACCTTTGAAATTGTACTGATGGTTT







CAGATATGTACGAAGGTCGTCACAACATTTTATCA







CTATGCACAGTTAGCACTTACCTGAATCCTCTGAA







GAAAAGAATAACATATTTATTGAGCCTTGTAGATA







ACTTAGCTTTTCAGATAGGTGATGCTGTATATAAC







ATAATTGCTTTGCTAGAATCCTTTGTATATGCACA







GTTGCAAATGTCAGATCCCATCCCAGAACTCAGAG







GACAATTCCATGCATTCGTATGTTCTGAGATTCTT







GATGCACTAAGGGGAACTAATAGTTTCACCCAGGA







TGAATCAAGAACTGTGACAACCAATTTGATATCCC







CATTCCAAGATCTGACCCCAGATCTTACGGCTGAA







TTGCTCTGTATAATGAGGCTTTGGGGACACCCCAT







GCTCACCGCCAGTCAAGCTGCGGGAAAGGTACGCG







AGTCCATGTGTGCTGGAAAAGTATTAGACTTTCCC







ACCATTATGAAAACACTAGCCTTTTTCCATACTAT







TCTGATCAATGGATACAGGAGGAAGCATCATGGAG







TATGGCCACCCTTAAACTTACCGGGTAATGCTTCA







AAGGGTCTCACGGAACTTATGAATGACAATACTGA







GATAAGCTATGAATTCACACTTAAGCATTGGAAGG







AAATCTCTCTTATAAAATTCAAGAAATGTTTTGAT







GCAGACGCAGGTGAGGAACTCAGTATATTTATGAA







AGATAAAGCAATTAGTGCCCCAAAACAAGATTGGA







TGAGTGTGTTTAGAAGAAGCCTAATCAAACAGCGC







CATCAGCATCATCAGGTCCCCCTACCAAATCCATT







CAATCGACGGCTATTGCTAAACTTTCTCGGAGATG







ACAAATTCGACCCGAATGTGGAGCTACAGTATGTA







ACATCAGGTGAGTATCTACATGATGACACGTTTTG







TGCATCATATTCACTAAAAGAGAAGGAAATTAAAC







CTGATGGTCGAATTTTTGCAAAGTTGACTAAGAGA







ATGAGATCATGTCAAGTTATAGCAGAATCTCTTTT







AGCGAACCATGCTGGGAAGTTAATGAAAGAGAATG







GTGTTGTGATGAATCAGCTATCATTAACAAAATCA







CTATTAACAATGAGTCAGATTGGAATAATATCCGA







GAAAGCTAGAAAATCGACTCGAGATAACATAAATC







AACCTGGTTTCCAGAATATCCAGAGAAATAAATCA







CATCACTCCAAGCAAGTCAATCAGCGAGATCCAAG







TGATGACTTTGAATTGGCAGCATCTTTTTTAACTA







CTGATCTCAAAAAATATTGTTTACAATGGAGGTAC







CAGACAATTATCCCATTTGCTCAATCATTAAACAG







AATGTATGGTTATCCTCATCTCTTTGAGTGGATTC







ACTTACGGCTAATGCGTAGTACACTTTACGTGGGG







GATCCCTTCAACCCACCAGCAGATACCAGTCAATT







TGATCTAGATAAAGTAATTAATGGAGATATCTTCA







TTGTATCACCCAGAGGTGGAATTGAAGGGCTATGT







CAAAAGGCTTGGACAATGATATCTATCTCTGTGAT







AATTCTATCTGCCACAGAGTCTGGCACACGAGTAA







TGAGTATGGTGCAGGGAGATAATCAAGCAATTGCT







GTCACCACACGAGTACCAAGGAGCCTGCCGACTCT







TGAGAAAAAGACTATTGCTTTTAGATCTTGTAATC







TATTCTTTGAGAGGTTAAAATGTAATAATTTTGGA







TTAGGTCACCATTTGAAAGAACAAGAGACTATCAT







TAGTTCTCACTTCTTTGTTTATAGCAAGAGAATAT







TCTATCAGGGGAGGATTCTAACGCAAGCCTTAAAA







AATGCTAGTAAGCTCTGCTTGACAGCTGATGTCCT







AGGAGAATGTACCCAATCATCATGTTCTAATCTTG







CAACTACTGTCATGAGGTTAACTGAGAATGGTGTT







GAAAAAGATATCTGTTTCTACTTGAATATCTATAT







GACCATCAAACAGCTCTCCTATGATATCATCTTCC







CTCAAGTGTCAATTCCTGGAGATCAGATCACATTA







GAATACATAAATAATCCACACCTGGTATCACGATT







GGCTCTTCTGCCATCCCAGCTAGGAGGTCTAAACT







ACCTGTCATGCAGTAGGCTGTTCAATCGAAACATA







GGCGACCCGGTGGTTTCCGCAGTTGCAGATCTTAA







GAGATTAATTAAATCAGGATGTATGGATTACTGGA







TCCTTTATAACTTATTAGGGAGAAAACCGGGAAAC







GGCTCATGGGCTACTTTAGCAGCTGACCCGTACTC







AATCAATATAGAGTATCAATACCCCCCAACTACAG







CTCTTAAGAGGCACACCCAACAAGCTCTGATGGAA







CTCAGTACGAATCCAATGTTACGTGGCATATTCTC







TGACAATGCACAGGCAGAAGAAAATAATCTTGCTA







GATTTCTCCTGGATAGGGAGGTGATCTTTCCGCGT







GTAGCTCACATCATCATTGAGCAAACCAGTGTCGG







GAGGAGAAAACAGATTCAAGGATATTTGGATTCAA







CTAGATCGATAATGAGTAAATCACTAGAAATTAAG







CCCTTGTCCAATAGGAAGCTTAATGAAATACTGGA







TTACAACATCAATTACCTAGCTTACAATTTGGCAT







TACTCAAGAATGCTATTGAACCTCCGACTTATTTG







AAAGCAATGACTCTTGAAACATGTAGCATCGACAT







TGCAAGGAGCCTCCGGAAGCTCTCCTGGGCCCCAC







TCTTGGGTGGGAGAAATCTTGAAGGATTAGAGACG







CCAGATCCCATTGAAATTACTGCAGGAGCATTAAT







TGTTGGATCGGGCTACTGTGAACAGTGTGCTGCAG







GAGACAATCGATTCACATGGTTTTTCTTGCCATCT







GGTATCGAGATAGGAGGGGATCCCCGTGATAATCC







TCCTATCCGTGTACCGTACATTGGCTCCAGGACTG







ATGAGAGGAGGGTAGCCTCAATGGCATACATCAGG







GGTGCCTCGAGTAGCCTAAAAGCAGTTCTTAGACT







GGCGGGAGTGTACATCTGGGCATTCGGAGATACTC







TGGAGAATTGGATAGATGCACTGGATTTGTCTCAC







ACTAGAGTTAACATCACACTTGAACAGCTGCAATC







CCTCACCCCACTTCCAACCTCTGCCAATCTAACCC







ATCGGTTGGATGATGGCACAACTACCCTAAAGTTT







ACTCCTGCGAGCTCTTACACCTTTTCAAGTTTCAC







TCATATATCAAATGATGAGCAATACCTGACAATTA







ATGACAAAACTGCAGATTCAAATATAATCTACCAA







CAGTTAATGATCACTGGACTCGGAATTTTAGAAAC







ATGGAATAATCCCCCAATCAATAGAACATTCGAAG







AATCTACCCTACATTTGCACACTGGTGCATCATGT







TGTGTCCGACCTGTGGACTCCTGCATCATCTCAGA







AGCATTAACAGTCAAGCCACATATTACAGTACCGT







ACAGCAATAAATTTGTATTTGATGAAGACCCGCTA







TCTGAATATGAGACTGCAAAACTGGAATCGTTATC







ATTTCAAGCCCAATTAGGCAACATTGATGCTGTAG







ATATGACAGGTAAATTAACATTATTGTCCCAATTC







ACTGCAAGGCAGATTATTAATGCAATCACTGGACT







CGATGAGTCTGTCTCTCTTACTAATGATGCCATTG







TTGCATCAGACTATGTCTCCAATTGGATTAGTGAA







TGCATGTATACCAAATTAGATGAATTATTTATGTA







TTGTGGGTGGGAACTACTATTGGAACTATCCTATC







AAATGTATTATCTGAGGGTAGTTGGGTGGAGTAAT







ATAGTGGATTATTCTTACATGATCTTGAGAAGAAT







CCCGGGTGCAGCATTAAACAATCTGGCATCTACAT







TAAGTCATCCAAAACTTTTCCGACGAGCTATCAAC







CTAGATATAGTTGCCCCCTTAAATGCTCCTCATTT







TGCATCTCTGGACTACATCAAGATGAGTGTGGATG







CAATACTCTGGGGCTGTAAAAGAGTCATCAATGTG







CTCTCCAATGGAGGGGACTTAGAATTAGTTGTGAC







ATCTGAAGATAGCCTTATTCTCAGTGACCGATCCA







TGAATCTCATTGCAAGGAAATTAACTTTATTATCA







CTGATTCACCATAATGGTTTGGAACTACCAAAGAT







TAAGGGGTTCTCTCCTGATGAGAAGTGTTTCGCTT







TGACAGAATTTTTGAGGAAAGTGGTGAACTCAGGG







TTGAGTTCAATAGAGAACCTATCAAATTTTATGTA







CAATGTGGAGAACCCACGGCTTGCAGCATTCGCCA







GCAACAATTACTACCTGACCAGAAAATTATTGAAT







TCAATACGAGATACTGAGTCGGGTCAAGTAGCAGT







CACCTCATATTATGAATCATTAGAATATATTGATA







GTCTTAAGCTAACCCCACATGTGCCTGGTACCTCA







TGCATTGAGGATGATAGTCTATGTACAAATGATTA







CATAATCTGGATCATAGAGTCTAATGCAAACTTGG







AGAAGTATCCAATTCCAAATAGCCCTGAGGATGAT







TCCAATTTCCATAACTTTAAGTTGAATGCTCCATC







GCACCATACCTTACGCCCATTAGGGTTGTCATCAA







CTGCTTGGTATAAGGGTATAAGCTGTTGCAGGTAC







CTTGAGCGATTAAAGCTACCACAAGGTGATCATTT







ATATATTGCAGAAGGTAGTGGTGCCAGTATGACAA







TCATAGAATACCTATTCCCAGGAAGAAAGATATAT







TACAATTCTTTATTTAGTAGTGGTGACAATCCCCC







ACAAAGAAATTATGCACCAATGCCTACTCAGTTCA







TTGAGAGTGTCCCATACAAGCTCTGGCAAGCACAC







ACAGATCAATATCCCGAGATTTTTGAGGACTTCAT







CCCTCTATGGAACGGAAATGCCGCCATGACTGACA







TAGGAATGACAGCTTGTGTAGAATTCATCATCAAT







CGAGTCGGCCCAAGGACTTGCAGTTTAGTACATGT







AGATTTGGAATCAAGTGCAAGCTTAAATCAACAAT







GCCTGTCAAAGCCGATAATTAATGCTATCATCACT







GCTACAACTGTTTTGTGCCCTCATGGGGTGCTTAT







TCTGAAATATAGTTGGTTGCCATTTACTAGATTTA







GTACTTTGATCACTTTCTTATGGTGCTACTTTGAG







AGAATCACTGTTCTTAGGAGCACATATTCTGGTCC







AGCTAATCATGAGGTTTATTTAATTTGTATCCTTG







CCAACAACTTTGCATTCCAGACTGTCTCGCAGGCA







ACAGGAATGGCGATGACTTTAACCGATCAAGGGTT







TACTTTGATATCACCTGAAAGAATAAATCAGTATT







GGGATGGTCACTTGAAGCAAGAACGTATCGTAGCA







GAAGCAATTGATAAGGTGGTTCTAGGAGAAGATGC







TCTATTCAATTCGAGTGATAATGAATTAATTCTCA







AATGTGGAGGGACACCAAATGCACGGAATCTTATC







GATATCGAGCCAGTCGCAACTTTCATAGAATTTGA







ACAACTGATCTGCACAATGTTGACAACCCACTTGA







AGGAAATAATTGATATAACAAGGTCTGGAACCCAG







GATTATGAAAGTTTATTACTCACTCCTTACAATTT







AGGTCTTCTTGGTAAAATCAGTACGATAGTGAGAT







TATTAACAGAAAGGATTCTAAATCATACTATCAGG







AATTGGTTGATCCTCCCACCTTCGCTCCGGATGAT







CGTGAAGCAGGACTTGGAATTCGGCATATTCAGGA







TTACTTCCATCCTCAATTCTGATCGGTTCCTGAAG







CTTTCTCCAAATAGGAAATACTTGATTACACAATT







AACTGCAGGCTACATTAGGAAATTGATTGAGGGGG







ATTGTAATATCGATCTAACCAGACCTATCCAAAAA







CAAATCTGGAAAGCATTAGGTTGTGTAGTCTATTG







TCACGATCCAGTAGATCAAAGGGAATCAACAGAGT







TTATTGATATAAATATTAATGAAGAAATAGACCGC







GGGATCGATGGCGAGGAAATCTAAATATATCAAGA







ATCAGAATTAGTTTAAGAAAAAAGAAGAGGATTAA







TCTTGGTTTTCCCCTTGGT.






4. CVL49


The nucleic acid sequence for CVL49 is:











(SEQ ID NO: 64)



ACCAGGGGGAAAACGAAGTGGTGACTCAAATCATC






GAAGACCCTCGAGATTACATAGGTCCGGAACCTAT






GGCCTTCGTGACCGACCTCGAGTCAGAGTAGTTCA






ATAAGGACCTATCAAGTTTGGGCAATTTTTCGTCC






CCGACACAAAAATGTCATCCGTGCTTAAAGCATAT






GAGCGATTCACACTCACTCAAGAACTGCAAGATCA






GAGTGAGGAAGGTACAATCCCACCTACAACACTAA






AACCGGTAATCAGGGTATTTATACTAACCTCTAAT






AACCCAGAGCTAAGATCCCGGCTTCTTCTATTCTG






CCTACGGATTGTTCTCAGTAATGGTGCAAGGGATT






CCCATCGCTTTGGAGCATTACTTACAATGTTTTCG






CTACCATCAGCCACAATGCTCAATCATGTCAAATT






AGCTGACCAGTCACCAGAAGCTGATATCGAAAGGG






TAGAGATCGATGGCTTTGAGGAGGGATCATTCCGC






TTAATCCCCAATGCTCGTTCAGGTATGAGCCGTGG






AGAGATCAATGCCTATGCTGCACTTGCAGAAGATC






TACCTGACACACTAAACCATGCAACACCTTTTGTT






GATTCCGAAGTCGAGGGAACTGCATGGGATGAGAT






TGAGACTTTCTTAGATATGTGTTACAGTGTCCTAA






TGCAGGCATGGATAGTGACTTGCAAGTGCATGACT






GCGCCAGACCAACCTGCTGCTTCTATTGAGAAACG






CCTGCAAAAATATCGTCAGCAAGGCAGGATCAACC






CGAGATATCTCCTGCAACCGGAGGCTCGAAGAATA






ATCCAGAATGTAATCCGAAAGGGAATGGTGGTCAG






ACATTTCCTCACCTTTGAACTGCAGCTTGCCCGAG






CACAAAGCCTTGTATCAAATAGGTATTATGCTATG






GTAGGGGATGTTGGAAAGTATATAGAGAATTGTGG






AATGGGAGGCTTCTTTTTGACACTAAAATATGCAT






TAGGAACCAGATGGCCCACACTTGCTTTAGCTGCA






TTTTCAGGAGAGCTAACAAAGCTAAAGTCCCTCAT






GGCATTATACCAGACCCTTGGTGAGCAGGCCCGAT






ATTTGGCCCTATTGGAGTCACCACATTTGATGGAT






TTTGCTGCAGCAAACTACCCACTGCTATATAGCTA






TGCTATGGGAATAGGCTATGTGTTAGATGTCAACA






TGAGGAACTACGCTTTCTCCAGATCATACATGAAT






AAGACATATTTCCAATTGGGAATGGAAACTGCAAG






AAAACAACAGGGTGCAGTTGACATGAGGATGGCAG






AAGATCTCGGTCTAACTCAAGCCGAACGCACCGAG






ATGGCAAATACACTTGCCAAATTGACCACAGCAAA






TCGAGGGGCAGACACCAGGGGAGGAGTCAACCCGT






TCTCATCTATCACTGGGACAACTCAGGTGCCCGCT






GCAGCAACAGGTGACACATTCGAGAGTTACATGGC






AGCGGATCGACTGAGGCAGAGATATGCTGATGCAG






GCACCCACGATGATGAGATGCCACCATTGGAAGAG






GAGGAAGAGGACGACACATCTGCAGGTCCACGCAC






TGGACTAACTCTTGAACAAGTGGCCTTGGACATCC






AGAACGCAGCAGTTGGAGCTCCCATCCATACAGAT






GACCTGAATGCCGCACTGGGTGATCTTGACATCTA






GACAATTCAGATCCCAATCTTAAATCGACACACCT






AATTGACCAGTTAGATGGAACTACAGTGGATTCCA






TAAGGTTCCTGCCTACCATCGGCTTTTAAGAAAAA






AATAGGCCCGGACGGGTTAGCAACAAGCGACTGCC






GATGCCAATAACACAATCCACAATCTACAATGGAT






CCCACTGATCTGAGCTTCTCCCCAGATGAGATCAA






TAAGCTCATAGAGACAGGCCTGAATACTGTGGAGT






ATTTTACTTCCCAACAAGTCACAGGAACATCCTCT






CTTGGAAAGAATACAATACCACCAGGGGTCACAGG






ACTACTAACCAATGCTGCAGAGGCAAAGATCCAAG






AGTCAACCAACCATCAGAAGGGTTCAGTTGGTGGG






GGCGCAAAACCAAAGAAACCGCGACCAAAAATTGC






CATTGTGCCAGCAGATGACAAAACGGTGCCCGGAA






AGCCGATCCCAAACCCTCTATTAGGTCTGGACTCC






ACCCCGAGCACCCAAACTGTGCTTGATCTAAGTGG






GAAAACATTACCATCAGGATCCTATAAGGGGGTTA






AACTTGCGAAATTTGGAAAAGAAAATCTGATGACA






CGGTTCATCGAGGAACCCAGAGAGAATCCTATCGC






AACCAATTCCCCCATCGATTTTAAGAGGGGCAGGG






ATACCGGCGGGTTCCATAGAAGGGAGTACTCAATC






GGATGGGTGGGAGATGAAGTCAAGGTCACTGAGTG






GTGCAATCCATCCTGTTCTCCAATCACCGCTGCAG






CAAGGCGATTTGAATGCACTTGTCACCAGTGTCCA






GTCACTTGCTCTGAATGTGAACGAGATACTTAATA






CAGTGAGAAATTTGGACTCTCGGATGAATCAACTG






GAGACAAAAGTAGATCGCATTCTCTCATCTCAGTC






TCTAATCCAGACCATCAAGAATGACATAGTTGGAC






TTAAAGCAGGGATGGCTACTTTAGAAGGAATGATT






ACAACTGTGAAAATCATGGACCCGGGAGTTCCCAG






TAATGTTACTGTGGAAGATGTACGCAAGAAACTAA






GTAACCATGCTGTTGTTGTGCCAGAATCATTCAAT






GATAGTTTCTTGACTCAATCTGAAGATGTAATTTC






ACTTGATGAGTTGGCTCGACCAACTGCAACAAGTG






TTAAGAAGATTGTCAGGAAGGTTCCTCCTCAGAAG






GATCTGACTGGATTGAAGATCACACTAGAGCAATT






GGCAAAGGATTGCATCAGCAAACCGAAGATGAGGG






AAGAGTATCTCCTCAAAATCAACCAGGCTTCCAGT






GAGGCTCAGCTAATTGACCTCAAGAAAGCAATCAT






CCGCAGTGCAATTTGATCAAGAAACACCCAATTAC






ACTACACTGGTATGACACTGTACTAACCCTGAGGG






TTTTAGAAAAAACGATTAACGATAAATAAGCCCGA






ACACTACACACCACCCGAGGCAGCCATGCCATCCA






TCAGCATCCCCGCAGACCCCACCAATCCACGTCAA






TCAATAAAAGCGTTCCCAATTGTGATCAACCGTGA






TGGGGGTGAGAAAGGTCGCTTGGTTAAACAACTAC






GCACAACCTACTTGAATGACCTAGATACTCATGAG






CCACTGGTGACATTCGTAAATACTTATGGATTCAT






CTACGAACAGGATCGGGGAAATACCATTGTCGGAG






AGGATCAACATGGGAAGAAAAGAGAGGCTGTGACT






GCTGCAATGGTTACCCTTGGATGTGGGCCTAATCT






ACCATCATTAGGGAATGTCCTGGGACAACTGAGTG






AATTCCAGGTCATTGTTAGGAAGACATCCAGCAAA






GCGGAAGAGATGGTCTTTGAAATTGTTAAGTATCC






GAGAATATTTCGGGGTCATACATTAATCCAGAAAG






GACTAGTCTGTGTCTCCGCAGAAAAATTTGTTAAG






TCACCAGGGAAAGTACAATCTGGAATGGACTATCT






CTTCATTCCGACATTTCTGTCAGTGACTTACTGTC






CAGCTGCAATCAAATTTCAGGTACCTGGCCCCATG






TTGAAAATGAGATCAAGATACACTCAGAGCTTACA






ACTTGAACTAATGATAAGAATCCTGTGTAAGCCCG






ATTCGCCACTTATGAAGGTCCATATCCCTGACAAG






GAAGGAAGAGGATGTCTTGTATCAGTATGGTTGCA






TGTATGCAATATCTTCAAATCAGGAAACAAGAATG






GCAGTGAGTGGCAGGAATACTGGATGAGAAAGTGT






GCTAACATGCAACTTGAAGTGTCGATTGCAGATAT






GTGGGGACCAACTATCATAATTCATGCCAGAGGTC






ACATTCCCAAAAGTGCTAAGTTGTTTTTTGGAAAG






GGTGGATGGAGCTGCCATCCACTTCACGAAGTTGT






TCCAAGTGTCACTAAAACACTATGGTCCGTGGGCT






GTGAGATTACAAAGGCGAAGGCAATAATACAAGAG






AGTAGCATCTCTCTTCTCGTGGAGACTACTGACAT






CATAAGTCCAAAAGTCAAAATTTCATCTAAGCATC






GCCGCTTTGGGAAATCAAATTGGGGTCTGTTCAAG






AAAACCAAATCACTGCCCAACCTGACGGAGCTGGA






ATGACTGACCCCCAATCGAGACTACACCACCTCAA






ACTATAGGTGGGTGGTACCTCAGTGATTAATCTCG






TAAGCACTGATCGTAGGCTACAACACACTAATATT






ATCCAGATTAGAGAGCTTAATTAGCTCTGTATTAA






TAATAACACTACTATTCCAATAACTGGAATCACCA






GCTTGATTTATCTCCAAAATGATTCAAAGAAAACA






AATCATATTAAGACTATCCTAAGCACGAACCCATA






TCGTCCTTCAAATCATGGGTACTATAATTCAATTT






CTGGTGGTCTCCTGTCTATTGGCAGGAGCAGGCAG






TCTTGATCCAGCAGCCCTCATGCAAATCGGTGTCA






TTCCAACAAATGTCCGGCAACTTATGTATTATACT






GAGGCCTCATCAGCATTCATTGTTGTGAAGTTAAT






GCCTACAATTGACTCGCCGATTAGTGGATGTAATA






TAACATCAATTTCAAGCTATAATGCAACAGTGACA






AAACTCCTACAGCCGATCGGTGAGAATTTGGAGAC






GATTAGGAACCAGTTGATTCCAACTCGGAGGAGAC






GCCGGTTTGCAGGGGTGGTGATTGGATTAGCTGCA






TTAGGAGTAGCTACTGCCGCACAGGTCACTGCCGC






AGTAGCACTAGTAAAGGCAAATGAAAATGCTGCGG






CTATACTCAATCTCAAAAATGCAATCCAAAAAACA






AATGCAGCAGTTGCAGATGTGGTCCAGGCCACACA






ATCACTAGGAACaGCAGTTCAAGCAGTTCAAGATC






ACATAAACAGTGTGGTAAGTCCAGCAATTACAGCA






GCCAATTGTAAAGCCCAAGATGCTATCATTGGCTC






AATCCTCAATCTCTATTTGACCGAGTTGACAACTA






TCTTCCACAATCAAATTACAAACCCTGCATTGAGT






CCTATTACAATTCAAGCTTTAAGGATCCTACTAGG






GAGTACCTTGCCGACTGTGGTCGAAAAATCTTTCA






ATACCCAGATAAGTGCGGCTGAGCTTCTCTCATCA






GGGTTATTGACAGGCCAGATTGTGGGATTAGATTT






GACCTATATGCAGATGGTCATAAAAATTGAGCTGC






CAACTTTAACTGTACAACCTGCAACCCAGATCATA






GATCTGGCCACCATTTCTGCATTCATTAACAATCA






AGAAGTCATGGCCCAATTACCAACACGTGTTATTG






TGACTGGCAGCTTGATCCAAGCCTATCCCGCATCG






CAATGCACTATTACACCCAACACTGTGTACTGTAG






GTATAATGATGCCCAAGTACTCTCAGATGATACGA






TGGCTTGCCTCCAAGGTAACTTGACAAGATGCACC






TTCTCTCCAGTGGTTGGGAGCTTTCTCACTCGATT






CGTGCTGTTCGATGGAATAGTTTATGCAAATTGCA






GGTCGATGTTGTGCAAGTGCATGCAGCCTGCTGCT






GTGATCCTACAGCCGAGTTCATCCCCTGTAACTGT






CATTGACATGTACAAATGTGTGAGTCTGCAGCTTG






ACAATCTCAGATTCACCATCACTCAATTGGCCAAT






GTAACCTACAATAGCACCATCAAGCTTGAAACATC






CCAGATCTTGCCTATTGATCCGTTGGATATATCCC






AGAATCTAGCTGCGGTGAATAAGAGTCTAAGTGAT






GCACTACAACACTTAGCACAAAGTGACACATACCT






TTCTGCAATCACATCAGCTACGACTACAAGTGTAT






TATCCATAATAGCAATCTGTCTTGGATCGTTAGGT






TTAATATTAATAATCTTGCTCAGTGTAGTTGTGTG






GAAGTTATTGACCATTGTCGCTGCTAATCGAAATA






GAATGGAGAATTTTGTTTATCATAATTCAGCATTC






CACCACTCACGATCTGATCTCAGTGAGAAAAATCA






ACCTGCAACTCTTGGAACAAGATAAGACAGTCATC






CATTAGTAATTTTTAAGAAAAAAACGATAGGACCG






AAACTAGTATTGAAAGAACCGTCTCGGTCAATCTA






GGTAATCGAGCTGcTACCGTCTCGGAAAGCTCAAA






TCATGCTGCCTGATCCGGAAGATCCGGAAAGCAAA






AAAGCTACAAGGAGAACAGGAAACCTAATTATCTG






CTTCCTATTCATCTTCTTTCCGTTTGTAAACTTCA






TTGTTCCAACTCTAAGACACTTGCTGTCCTAACAC






CTGCTATAGGCTATCCACTGCATCATCTCTTTTTA






AGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGC






GACTGCCGGTGCCAACAACACAATCCACAATCTAC






AGTCGACGCGGCCGCCatgttcgtcttcctggtcc






tgctgcctctggtctcctcacagtgcgtcaatTTC






acaaAccggactcagctgccaTctgcttatactaa






tagcttcaccagaggcgtgtactatcctgacaagg






tgtttagaagctccgtgctgcactctacacaggat






ctgtttctgccattctttagcaacgtgacctggtt






ccacgccatccacgtgagcggcaccaatggcacaa






agcggttcgacaatcccgtgctgccttttaacgat






ggcgtgtacttcgcctctaccgagaagagcaacat






catcagaggctggatctttggcaccacactggact






ccaagacacagtctctgctgatcgtgaacaatgcc






accaacgtggtcatcaaggtgtgcgagttccagtt






ttgtaatTACcccttcctgggcgtgtactatcaca






agaacaataagagctggatggagtccgagtttaga






gtgtattctagcgccaacaactgcacatttgagta






cgtgagccagcctttcctgatggacctggagggca






agcagggcaatttcaagaacctgagCgagttcgtg






tttaagaatatcgacggctacttcaaaatctactc






taagcacacccccatcaacctggtgcgcgacctgc






ctcagggcttcagcgccctggagcccctggtggat






ctgcctatcggcatcaacatcacccggtttcagac






actgctggccctgcacagaagctacctgacacccg






gcgactcctctagcggatggaccgccggcgctgcc






gcctactatgtgggctacctccagccccggacctt






cctgctgaagtacaacgagaatggcaccatcacag






acgcagtggattgcgccctggaTcccctgagcgag






acaaagtgtacactgaagtcctttaccgtggagaa






gggcatctatcagacatccaatttcagggtgcagc






caaccgagtctatcgtgcgctttcctaatatcaca






aacctgtgcccatttggcgaggtgttcaacgcaac






ccgcttcgccagcgtgtacgcctggaataggaagc






ggatcagcaactgcgtggccgactatagcgtgctg






tacaactccgcctctttcagcacctttaagtgcta






tggcgtgtcccccacaaagctgaatgacctgtgct






ttaccaacgtctacgccgattctttcgtgatcagg






ggcgacgaggtgcgccagatcgcccccggccagac






aggcaCgatcgcagactacaattataagctgccag






acgatttcaccggctgcgtgatcgcctggaacagc






aacaatctggattccaaagtgggcggcaactacaa






ttatctgtaccggctgtttagaaagagcaatctga






agcccttcgagagggacatctctacagaaatctac






caggccggcagcaccccttgcaatggcgtgAaggg






ctttaactgttatttcccactccagtcctacggct






tccagcccacaTacggcgtgggctatcagccttac






cgcgtggtggtgctgagctttgagctgctgcacgc






cccagcaacagtgtgcggccccaagaagtccacca






atctggtgaagaacaagtgcgtgaacttcaacttc






aacggcctgaccggcacaggcgtgctgaccgagtc






caacaagaagttcctgccatttcagcagttcggca






gggacatcgcagataccacagacgccgtgcgcgac






ccacagaccctggagatcctggacatcacaccctg






ctctttcggcggcgtgagcgtgatcacacccggca






ccaatacaagcaaccaggtggccgtgctgtatcag






gGcgtgaattgtaccgaggtgcccgtggctatcca






cgccgatcagctgaccccaacatggcgggtgtaca






gcaccggctccaacgtcttccagacaagagccgga






tgcctgatcggagcagagTacgtgaacaattccta






tgagtgcgacatcccaatcggcgccggcatctgtg






cctcttaccagacccagacaaactctcccagaaga






gcccggagcgtggcctcccagtctatcatcgccta






taccatgtccctgggcgccgagaacagcgtggcct






actctaacaatagcatcgccatcccaaccaacttc






acaatctctgtgaccacagagatcctgcccgtgtc






catgaccaagacatctgtggactgcacaatgtata






tctgtggcgattctaccgagtgcagcaacctgctg






ctccagtacggcagcttttgtacccagctgaatag






agccctgacaggcatcgccgtggagcaggataaga






acacacaggaggtgttcgcccaggtgaagcaaatc






tacaagaccccccctatcaaggactttggcggctt






caatttttcccagatcctgcctgatccatccaagc






cttctaagcggagctttatcgaggacctgctgttc






aacaaggtgaccctggccgatgccggcttcatcaa






gcagtatggcgattgcctgggcgacatcgcagcca






gggacctgatctgcgcccagaagtttaatggcctg






accgtgctgccacccctgctgacagatgagatgat






cgcacagtacacaagcgccctgctggccggcacca






tcacatccggatggaccttcggcgcaggagccgcc






ctccagatcccctttgccatgcagatggcctatag






gttcaacggcatcggcgtgacccagaatgtgctgt






acgagaaccagaagctgatcgccaatcagtttaac






tccgccatcggcaagatccaggacagcctgtcctc






tacagccagcgccctgggcaagctccaggatgtgg






tgaatcagaacgcccaggccctgaataccctggtg






aagcagctgagcagcaacttcggcgccatctctag






cgtgctgaatgacatcctgagccggctggacaagg






tggaggcagaggtgcagatcgaccggctgatcacc






ggccggctccagagcctccagacctatgtgacaca






gcagctgatcagggccgccgagatcagggccagcg






ccaatctggcagcaaTTaagatgtccgagtgcgtg






ctgggccagtctaagagagtggacttttgtggcaa






gggctatcacctgatgtccttccctcagtctgccc






cacacggcgtggtgtttctgcacgtgacctacgtg






cccgcccaggagaagaacttcaccacagcccctgc






catctgccacgatggcaaggcccactttccaaggg






agggcgtgttcgtgtccaacggcacccactggttt






gtgacacagcgcaatttctacgagccccagatcat






caccacagacaacaccttcgtgagcggcaactgtg






acgtggtcatcggcatcgtgaacaataccgtgtat






gatccactccagcccgagctggacagctttaagga






ggagctggataagtatttcaagaatcacacctccc






ctgacgtggatctgggcgacatcagcggcatcaat






gcctccTTTgtgaacatccagaaggagatcgaccg






cctgaacgaggtggctaagaatctgaacgagagcc






tgatcgacctccaggagctgggcaagtatgagcag






tacatcaagtggccctggtacatctggctgggctt






catcgccggcctgatcgccatcgtgatggtgacca






tcatgctgtgctgtatgacatcctgctgttcttgc






ctgaagggctgctgtagctgtggctcctgctgtAA






GTTATTGACCATTGTCGTTGCTAATCGAAATAGAA






TGGAGAATTTTGTTTATCATAAATGAGCTAGCCTC






CTGCCATACTTCCTACTCACATCATATCTATTTTA






AAGAAAAAATAGGCCCGAACACTAATCGTGCCGGC






AGTGCCACTGCACACACAACACTACACATACAATA






CACTACAATGGTTGCAGAAGATGCCCCTGTTAGGG






GCACTTGCCGAGTATTATTTCGAACAACAACTTTA






ATTTTTCTATGCACACTATTAGCATTAAGCATCTC






TATCCTTTATGAGAGTTTAATAACCCAAAAGCAAA






TCATGAGCCAAGCAGGCTCAACTGGATCTAATTCT






AGATTAGGAAGTATCACTGATCTTCTTAATAATAT






TCTCTCTGTCGCAAATCAGATTATATATAACTCTG






CAGTCGCTCTACCTCTACAATTGGACACTCTTGAA






TCAACACTCCTTACAGCCATTAAGTCTCTTCAAAC






AAGTGACAAGCTAGAACAGAACTGCTCGTGGGGTG






CTGCACTGATTAATGATAATAGATACATTAATGGC






ATCAATCAGTTCTATTTCTCAATTGCTGAGGGTCG






CAAGCTGACACTTGGCCCACTTCTTAATATACCTA






GTTTCATTCCAACTGCCACGACACCAGAGGGCTGC






ACCAGGATCCCATCATTCTCGCTCACCAAGACACA






CTGGTGTTATACACACAATGTTATCCTGAATGGAT






GCCAGGATCATGTATCCTCAAATCAATTTGTTTCC






ATGGGAATCATTGAACCCACTTCTGCCGGGTTTCC






ATCCTTTCGAACCCTAAAGACTCTATATCTCAGCG






ATGGGGTCAATCGTAAGAGCTGCTCTATCAGTACA






GTTCCGGGGGGTTGTATGATGTACTGTTTCGTCTC






TACTCAACCAGAGAGGGATGACTACTTTTCTACCG






CTCCTCCAGAACAACGAATTATTATAATGTACTAT






AATGATACAATCGTGGAGCGCATAATTAATCCACC






CGGGGTACTAGATGTATGGGCAACATTGAACCCAG






GAACAGGAAGCGGGGTATATTATTTAGGTTGGGTA






CTCTTTCCAATATATGGCGGCGTGATTAAAGATAC






GAGTTTATGGAATAATCAAGCAAATAAATACTTTA






TCCCCCAGATGGTTGCTGCTCTCTGCTCACAAAAC






CAGGCAACTCAAGTCCAAAATGCTAAGTCATCATA






CTATAGCAGCTGGTTTGGCAATCGAATGATTCAGT






CTGGGATCCTGGCATGTCCTCTTCAACAGGATCTA






ACCAATGAGTGTTTAGTTCTGCCCTTTTCTAATGA






TCAGGTGCTTATGGGTGCTGAAGGGAGATTATACA






TGTATGGTGACTCGGTGTATTACTACCAAAGAAGC






AATAGTTGGTGGCCTATGACCATGCTGTATAAGGT






AACCATAACATTCACTAATGGTCAGCCATCTGCTA






TATCAGCTCAGAATGTGCCCACACAGCAGGTCCCT






AGACCTGGGACAGGAAGCTGCTCTGCAACAAATAG






ATGTCCCGGTTTTTGCTTGAAAGGAGTGTATGCTG






ATGCCTGGTTACTGACCAACCCTTCGTCTACCAGT






ACATTTGGATCAGAAGCAACCTTCACTGGTTCTTA






TCTCAACGCAGCAACTCAGCGTATCAATCCGACGA






TGTATATCGCGAACAACACACAGATCATAAGCTCA






CAGCAATTTGGATCAAGCGGTCAAGAAGCAGCATA






TGGCCACACAACTTGTTTTAGGGACACAGGCTCTG






TTATGGTATACTGTATCTATATTATTGAATTGTCC






TCATCTCTCTTAGGACAATTTCAGATTGTCCCATT






TATCCGTCAGGTGACACTATCCTAAAGGCAGAAGC






CTCCAGGTCTGACCCAGCCAATCAAAGCATTATAC






CAGACCATGGAATGCATACCAAACATTATTGACAC






TAATGACACACAAAATTGGTTTTAAGAAAAACCAA






GAGAACAATAGGCCAGAATGGCTGGGTCTCGGGAG






ATATTACTCCCTGAAGTCCATCTCAATTCACCAAT






TGTAAAGCATAAGCTATACTATTACATTCTACTTG






GAAACCTCCCAAATGAGATCGACATTGACGATTTA






GGTCCATTACATAATCAAAATTGGAATCAAATAGC






ACATGAAGAGTCTAACTTAGCCCAACGCTTGGTAA






ATGTAAGAAATTTTCTAATTACCCACATCCCTGAT






CTTAGAAAGGGCCATTGGCAAGAGTATGTCAATGT






AATACTGTGGCCGCGAATTCTTCCCTTGATCCCGG






ATTTTAAAATCAATGACCAATTGCCTCTACTCAAA






AATTGGGACAAGTTAGTTAAAGAATCATGTTCAGT






AATCAATGCGGGTACTTCCCAGTGCATTCAGAATC






TCAGCTATGGACTGACAGGTCGTGGGAACCTCTTT






ACACGATCACGTGAACTCTCTGGTGACCGCAGGGA






TATTGATCTTAAGACGGTTGTGGCAGCATGGCATG






ACTCAGACTGGAAAAGAATAAGTGATTTTTGGATT






ATGATCAAATTCCAGATGAGACAATTAATTGTTAG






GCAAACAGATCATAATGATCCTGATTTAATCACGT






ATATCGAAAATAGAGAAGGCATAATCATCATAACC






CCTGAACTGGTAGCATTATTTAACACTGAGAATCA






TACACTAACATACATGACCTTTGAAATTGTACTGA






TGGTTTCAGATATGTACGAAGGTCGTCACAACATT






TTATCACTATGCACAGTTAGCACTTACCTGAATCC






TCTGAAGAAAAGAATAACATATTTATTGAGCCTTG






TAGATAACTTAGCTTTTCAGATAGGTGATGCTGTA






TATAACATAATTGCTTTGCTAGAATCCTTTGTATA






TGCACAGTTGCAAATGTCAGATCCCATCCCAGAAC






TCAGAGGACAATTCCATGCATTCGTATGTTCTGAG






ATTCTTGATGCACTAAGGGGAACTAATAGTTTCAC






CCAGGATGAATCAAGAACTGTGACAACCAATTTGA






TATCCCCATTCCAAGATCTGACCCCAGATCTTACG






GCTGAATTGCTCTGTATAATGAGGCTTTGGGGACA






CCCCATGCTCACCGCCAGTCAAGCTGCGGGAAAGG






TACGCGAGTCCATGTGTGCTGGAAAAGTATTAGAC






TTTCCCACCATTATGAAAACACTAGCCTTTTTCCA






TACTATTCTGATCAATGGATACAGGAGGAAGCATC






ATGGAGTATGGCCACCCTTAAACTTACCGGGTAAT






GCTTCAAAGGGTCTCACGGAACTTATGAATGACAA






TACTGAGATAAGCTATGAATTCACACTTAAGCATT






GGAAGGAAATCTCTCTTATAAAATTCAAGAAATGT






TTTGATGCAGACGCAGGTGAGGAACTCAGTATATT






TATGAAAGATAAAGCAATTAGTGCCCCAAAACAAG






ATTGGATGAGTGTGTTTAGAAGAAGCCTAATCAAA






CAGCGCCATCAGCATCATCAGGTCCCCCTACCAAA






TCCATTCAATCGACGGCTATTGCTAAACTTTCTCG






GAGATGACAAATTCGACCCGAATGTGGAGCTACAG






TATGTAACATCAGGTGAGTATCTACATGATGACAC






GTTTTGTGCATCATATTCACTAAAAGAGAAGGAAA






TTAAACCTGATGGTCGAATTTTTGCAAAGTTGACT






AAGAGAATGAGATCATGTCAAGTTATAGCAGAATC






TCTTTTAGCGAACCATGCTGGGAAGTTAATGAAAG






AGAATGGTGTTGTGATGAATCAGCTATCATTAACA






AAATCACTATTAACAATGAGTCAGATTGGAATAAT






ATCCGAGAAAGCTAGAAAATCGACTCGAGATAACA






TAAATCAACCTGGTTTCCAGAATATCCAGAGAAAT






AAATCACATCACTCCAAGCAAGTCAATCAGCGAGA






TCCAAGTGATGACTTTGAATTGGCAGCATCTTTTT






TAACTACTGATCTCAAAAAATATTGTTTACAATGG






AGGTACCAGACAATTATCCCATTTGCTCAATCATT






AAACAGAATGTATGGTTATCCTCATCTCTTTGAGT






GGATTCACTTACGGCTAATGCGTAGTACACTTTAC






GTGGGGGATCCCTTCAACCCACCAGCAGATACCAG






TCAATTTGATCTAGATAAAGTAATTAATGGAGATA






TCTTCATTGTATCACCCAGAGGTGGAATTGAAGGG






CTATGTCAAAAGGCTTGGACAATGATATCTATCTC






TGTGATAATTCTATCTGCCACAGAGTCTGGCACAC






GAGTAATGAGTATGGTGCAGGGAGATAATCAAGCA






ATTGCTGTCACCACACGAGTACCAAGGAGCCTGCC






GACTCTTGAGAAAAAGACTATTGCTTTTAGATCTT






GTAATCTATTCTTTGAGAGGTTAAAATGTAATAAT






TTTGGATTAGGTCACCATTTGAAAGAACAAGAGAC






TATCATTAGTTCTCACTTCTTTGTTTATAGCAAGA






GAATATTCTATCAGGGGAGGATTCTAACGCAAGCC






TTAAAAAATGCTAGTAAGCTCTGCTTGACAGCTGA






TGTCCTAGGAGAATGTACCCAATCATCATGTTCTA






ATCTTGCAACTACTGTCATGAGGTTAACTGAGAAT






GGTGTTGAAAAAGATATCTGTTTCTACTTGAATAT






CTATATGACCATCAAACAGCTCTCCTATGATATCA






TCTTCCCTCAAGTGTCAATTCCTGGAGATCAGATC






ACATTAGAATACATAAATAATCCACACCTGGTATC






ACGATTGGCTCTTCTGCCATCCCAGCTAGGAGGTC






TAAACTACCTGTCATGCAGTAGGCTGTTCAATCGA






AACATAGGCGACCCGGTGGTTTCCGCAGTTGCAGA






TCTTAAGAGATTAATTAAATCAGGATGTATGGATT






ACTGGATCCTTTATAACTTATTAGGGAGAAAACCG






GGAAACGGCTCATGGGCTACTTTAGCAGCTGACCC






GTACTCAATCAATATAGAGTATCAATACCCCCCAA






CTACAGCTCTTAAGAGGCACACCCAACAAGCTCTG






ATGGAACTCAGTACGAATCCAATGTTACGTGGCAT






ATTCTCTGACAATGCACAGGCAGAAGAAAATAATC






TTGCTAGATTTCTCCTGGATAGGGAGGTGATCTTT






CCGCGTGTAGCTCACATCATCATTGAGCAAACCAG






TGTCGGGAGGAGAAAACAGATTCAAGGATATTTGG






ATTCAACTAGATCGATAATGAGTAAATCACTAGAA






ATTAAGCCCTTGTCCAATAGGAAGCTTAATGAAAT






ACTGGATTACAACATCAATTACCTAGCTTACAATT






TGGCATTACTCAAGAATGCTATTGAACCTCCGACT






TATTTGAAAGCAATGACTCTTGAAACATGTAGCAT






CGACATTGCAAGGAGCCTCCGGAAGCTCTCCTGGG






CCCCACTCTTGGGTGGGAGAAATCTTGAAGGATTA






GAGACGCCAGATCCCATTGAAATTACTGCAGGAGC






ATTAATTGTTGGATCGGGCTACTGTGAACAGTGTG






CTGCAGGAGACAATCGATTCACATGGTTTTTCTTG






CCATCTGGTATCGAGATAGGAGGGGATCCCCGTGA






TAATCCTCCTATCCGTGTACCGTACATTGGCTCCA






GGACTGATGAGAGGAGGGTAGCCTCAATGGCATAC






ATCAGGGGTGCCTCGAGTAGCCTAAAAGCAGTTCT






TAGACTGGCGGGAGTGTACATCTGGGCATTCGGAG






ATACTCTGGAGAATTGGATAGATGCACTGGATTTG






TCTCACACTAGAGTTAACATCACACTTGAACAGCT






GCAATCCCTCACCCCACTTCCAACCTCTGCCAATC






TAACCCATCGGTTGGATGATGGCACAACTACCCTA






AAGTTTACTCCTGCGAGCTCTTACACCTTTTCAAG






TTTCACTCATATATCAAATGATGAGCAATACCTGA






CAATTAATGACAAAACTGCAGATTCAAATATAATC






TACCAACAGTTAATGATCACTGGACTCGGAATTTT






AGAAACATGGAATAATCCCCCAATCAATAGAACAT






TCGAAGAATCTACCCTACATTTGCACACTGGTGCA






TCATGTTGTGTCCGACCTGTGGACTCCTGCATCAT






CTCAGAAGCATTAACAGTCAAGCCACATATTACAG






TACCGTACAGCAATAAATTTGTATTTGATGAAGAC






CCGCTATCTGAATATGAGACTGCAAAACTGGAATC






GTTATCATTTCAAGCCCAATTAGGCAACATTGATG






CTGTAGATATGACAGGTAAATTAACATTATTGTCC






CAATTCACTGCAAGGCAGATTATTAATGCAATCAC






TGGACTCGATGAGTCTGTCTCTCTTACTAATGATG






CCATTGTTGCATCAGACTATGTCTCCAATTGGATT






AGTGAATGCATGTATACCAAATTAGATGAATTATT






TATGTATTGTGGGTGGGAACTACTATTGGAACTAT






CCTATCAAATGTATTATCTGAGGGTAGTTGGGTGG






AGTAATATAGTGGATTATTCTTACATGATCTTGAG






AAGAATCCCGGGTGCAGCATTAAACAATCTGGCAT






CTACATTAAGTCATCCAAAACTTTTCCGACGAGCT






ATCAACCTAGATATAGTTGCCCCCTTAAATGCTCC






TCATTTTGCATCTCTGGACTACATCAAGATGAGTG






TGGATGCAATACTCTGGGGCTGTAAAAGAGTCATC






AATGTGCTCTCCAATGGAGGGGACTTAGAATTAGT






TGTGACATCTGAAGATAGCCTTATTCTCAGTGACC






GATCCATGAATCTCATTGCAAGGAAATTAACTTTA






TTATCACTGATTCACCATAATGGTTTGGAACTACC






AAAGATTAAGGGGTTCTCTCCTGATGAGAAGTGTT






TCGCTTTGACAGAATTTTTGAGGAAAGTGGTGAAC






TCAGGGTTGAGTTCAATAGAGAACCTATCAAATTT






TATGTACAATGTGGAGAACCCACGGCTTGCAGCAT






TCGCCAGCAACAATTACTACCTGACCAGAAAATTA






TTGAATTCAATACGAGATACTGAGTCGGGTCAAGT






AGCAGTCACCTCATATTATGAATCATTAGAATATA






TTGATAGTCTTAAGCTAACCCCACATGTGCCTGGT






ACCTCATGCATTGAGGATGATAGTCTATGTACAAA






TGATTACATAATCTGGATCATAGAGTCTAATGCAA






ACTTGGAGAAGTATCCAATTCCAAATAGCCCTGAG






GATGATTCCAATTTCCATAACTTTAAGTTGAATGC






TCCATCGCACCATACCTTACGCCCATTAGGGTTGT






CATCAACTGCTTGGTATAAGGGTATAAGCTGTTGC






AGGTACCTTGAGCGATTAAAGCTACCACAAGGTGA






TCATTTATATATTGCAGAAGGTAGTGGTGCCAGTA






TGACAATCATAGAATACCTATTCCCAGGAAGAAAG






ATATATTACAATTCTTTATTTAGTAGTGGTGACAA






TCCCCCACAAAGAAATTATGCACCAATGCCTACTC






AGTTCATTGAGAGTGTCCCATACAAGCTCTGGCAA






GCACACACAGATCAATATCCCGAGATTTTTGAGGA






CTTCATCCCTCTATGGAACGGAAATGCCGCCATGA






CTGACATAGGAATGACAGCTTGTGTAGAATTCATC






ATCAATCGAGTCGGCCCAAGGACTTGCAGTTTAGT






ACATGTAGATTTGGAATCAAGTGCAAGCTTAAATC






AACAATGCCTGTCAAAGCCGATAATTAATGCTATC






ATCACTGCTACAACTGTTTTGTGCCCTCATGGGGT






GCTTATTCTGAAATATAGTTGGTTGCCATTTACTA






GATTTAGTACTTTGATCACTTTCTTATGGTGCTAC






TTTGAGAGAATCACTGTTCTTAGGAGCACATATTC






TGGTCCAGCTAATCATGAGGTTTATTTAATTTGTA






TCCTTGCCAACAACTTTGCATTCCAGACTGTCTCG






CAGGCAACAGGAATGGCGATGACTTTAACCGATCA






AGGGTTTACTTTGATATCACCTGAAAGAATAAATC






AGTATTGGGATGGTCACTTGAAGCAAGAACGTATC






GTAGCAGAAGCAATTGATAAGGTGGTTCTAGGAGA






AGATGCTCTATTCAATTCGAGTGATAATGAATTAA






TTCTCAAATGTGGAGGGACACCAAATGCACGGAAT






CTTATCGATATCGAGCCAGTCGCAACTTTCATAGA






ATTTGAACAACTGATCTGCACAATGTTGACAACCC






ACTTGAAGGAAATAATTGATATAACAAGGTCTGGA






ACCCAGGATTATGAAAGTTTATTACTCACTCCTTA






CAATTTAGGTCTTCTTGGTAAAATCAGTACGATAG






TGAGATTATTAACAGAAAGGATTCTAAATCATACT






ATCAGGAATTGGTTGATCCTCCCACCTTCGCTCCG






GATGATCGTGAAGCAGGACTTGGAATTCGGCATAT






TCAGGATTACTTCCATCCTCAATTCTGATCGGTTC






CTGAAGCTTTCTCCAAATAGGAAATACTTGATTAC






ACAATTAACTGCAGGCTACATTAGGAAATTGATTG






AGGGGGATTGTAATATCGATCTAACCAGACCTATC






CAAAAACAAATCTGGAAAGCATTAGGTTGTGTAGT






CTATTGTCACGATCCAGTAGATCAAAGGGAATCAA






CAGAGTTTATTGATATAAATATTAATGAAGAAATA






GACCGCGGGATCGATGGCGAGGAAATCTAAATATA






TCAAGAATCAGAATTAGTTTAAGAAAAAAGAAGAG






GATTAATCTTGGTTTTCCCCTTGGT.






5. CVL50


The nucleic acid sequence for CVL50 is:











(SEQ ID NO: 65)



ACCAGGGGGAAAACGAAGTGGTGACTCAAATCATC







GAAGACCCTCGAGATTACATAGGTCCGGAACCTAT







GGCCTTCGTGACCGACCTCGAGTCAGAGTAGTTCA







ATAAGGACCTATCAAGTTTGGGCAATTTTTCGTCC







CCGACACAAAAATGTCATCCGTGCTTAAAGCATAT







GAGCGATTCACACTCACTCAAGAACTGCAAGATCA







GAGTGAGGAAGGTACAATCCCACCTACAACACTAA







AACCGGTAATCAGGGTATTTATACTAACCTCTAAT







AACCCAGAGCTAAGATCCCGGCTTCTTCTATTCTG







CCTACGGATTGTTCTCAGTAATGGTGCAAGGGATT







CCCATCGCTTTGGAGCATTACTTACAATGTTTTCG







CTACCATCAGCCACAATGCTCAATCATGTCAAATT







AGCTGACCAGTCACCAGAAGCTGATATCGAAAGGG







TAGAGATCGATGGCTTTGAGGAGGGATCATTCCGC







TTAATCCCCAATGCTCGTTCAGGTATGAGCCGTGG







AGAGATCAATGCCTATGCTGCACTTGCAGAAGATC







TACCTGACACACTAAACCATGCAACACCTTTTGTT







GATTCCGAAGTCGAGGGAACTGCATGGGATGAGAT







TGAGACTTTCTTAGATATGTGTTACAGTGTCCTAA







TGCAGGCATGGATAGTGACTTGCAAGTGCATGACT







GCGCCAGACCAACCTGCTGCTTCTATTGAGAAACG







CCTGCAAAAATATCGTCAGCAAGGCAGGATCAACC







CGAGATATCTCCTGCAACCGGAGGCTCGAAGAATA







ATCCAGAATGTAATCCGAAAGGGAATGGTGGTCAG







ACATTTCCTCACCTTTGAACTGCAGCTTGCCCGAG







CACAAAGCCTTGTATCAAATAGGTATTATGCTATG







GTAGGGGATGTTGGAAAGTATATAGAGAATTGTGG







AATGGGAGGCTTCTTTTTGACACTAAAATATGCAT







TAGGAACCAGATGGCCCACACTTGCTTTAGCTGCA







TTTTCAGGAGAGCTAACAAAGCTAAAGTCCCTCAT







GGCATTATACCAGACCCTTGGTGAGCAGGCCCGAT







ATTTGGCCCTATTGGAGTCACCACATTTGATGGAT







TTTGCTGCAGCAAACTACCCACTGCTATATAGCTA







TGCTATGGGAATAGGCTATGTGTTAGATGTCAACA







TGAGGAACTACGCTTTCTCCAGATCATACATGAAT







AAGACATATTTCCAATTGGGAATGGAAACTGCAAG







AAAACAACAGGGTGCAGTTGACATGAGGATGGCAG







AAGATCTCGGTCTAACTCAAGCCGAACGCACCGAG







ATGGCAAATACACTTGCCAAATTGACCACAGCAAA







TCGAGGGGCAGACACCAGGGGAGGAGTCAACCCGT







TCTCATCTATCACTGGGACAACTCAGGTGCCCGCT







GCAGCAACAGGTGACACATTCGAGAGTTACATGGC







AGCGGATCGACTGAGGCAGAGATATGCTGATGCAG







GCACCCACGATGATGAGATGCCACCATTGGAAGAG







GAGGAAGAGGACGACACATCTGCAGGTCCACGCAC







TGGACTAACTCTTGAACAAGTGGCCTTGGACATCC







AGAACGCAGCAGTTGGAGCTCCCATCCATACAGAT







GACCTGAATGCCGCACTGGGTGATCTTGACATCTA







GACAATTCAGATCCCAATCTTAAATCGACACACCT







AATTGACCAGTTAGATGGAACTACAGTGGATTCCA







TAAGGTTCCTGCCTACCATCGGCTTTTAAGAAAAA







AATAGGCCCGGACGGGTTAGCAACAAGCGACTGCC







GATGCCAATAACACAATCCACAATCTACAATGGAT







CCCACTGATCTGAGCTTCTCCCCAGATGAGATCAA







TAAGCTCATAGAGACAGGCCTGAATACTGTGGAGT







ATTTTACTTCCCAACAAGTCACAGGAACATCCTCT







CTTGGAAAGAATACAATACCACCAGGGGTCACAGG







ACTACTAACCAATGCTGCAGAGGCAAAGATCCAAG







AGTCAACCAACCATCAGAAGGGTTCAGTTGGTGGG







GGCGCAAAACCAAAGAAACCGCGACCAAAAATTGC







CATTGTGCCAGCAGATGACAAAACGGTGCCCGGAA







AGCCGATCCCAAACCCTCTATTAGGTCTGGACTCC







ACCCCGAGCACCCAAACTGTGCTTGATCTAAGTGG







GAAAACATTACCATCAGGATCCTATAAGGGGGTTA







AACTTGCGAAATTTGGAAAAGAAAATCTGATGACA







CGGTTCATCGAGGAACCCAGAGAGAATCCTATCGC







AACCAATTCCCCCATCGATTTTAAGAGGGGCAGGG







ATACCGGCGGGTTCCATAGAAGGGAGTACTCAATC







GGATGGGTGGGAGATGAAGTCAAGGTCACTGAGTG







GTGCAATCCATCCTGTTCTCCAATCACCGCTGCAG







CAAGGCGATTTGAATGCACTTGTCACCAGTGTCCA







GTCACTTGCTCTGAATGTGAACGAGATACTTAATA







CAGTGAGAAATTTGGACTCTCGGATGAATCAACTG







GAGACAAAAGTAGATCGCATTCTCTCATCTCAGTC







TCTAATCCAGACCATCAAGAATGACATAGTTGGAC







TTAAAGCAGGGATGGCTACTTTAGAAGGAATGATT







ACAACTGTGAAAATCATGGACCCGGGAGTTCCCAG







TAATGTTACTGTGGAAGATGTACGCAAGAAACTAA







GTAACCATGCTGTTGTTGTGCCAGAATCATTCAAT







GATAGTTTCTTGACTCAATCTGAAGATGTAATTTC







ACTTGATGAGTTGGCTCGACCAACTGCAACAAGTG







TTAAGAAGATTGTCAGGAAGGTTCCTCCTCAGAAG







GATCTGACTGGATTGAAGATCACACTAGAGCAATT







GGCAAAGGATTGCATCAGCAAACCGAAGATGAGGG







AAGAGTATCTCCTCAAAATCAACCAGGCTTCCAGT







GAGGCTCAGCTAATTGACCTCAAGAAAGCAATCAT







CCGCAGTGCAATTTGATCAAGAAACACCCAATTAC







ACTACACTGGTATGACACTGTACTAACCCTGAGGG







TTTTAGAAAAAACGATTAACGATAAATAAGCCCGA







ACACTACACACCACCCGAGGCAGCCATGCCATCCA







TCAGCATCCCCGCAGACCCCACCAATCCACGTCAA







TCAATAAAAGCGTTCCCAATTGTGATCAACCGTGA







TGGGGGTGAGAAAGGTCGCTTGGTTAAACAACTAC







GCACAACCTACTTGAATGACCTAGATACTCATGAG







CCACTGGTGACATTCGTAAATACTTATGGATTCAT







CTACGAACAGGATCGGGGAAATACCATTGTCGGAG







AGGATCAACATGGGAAGAAAAGAGAGGCTGTGACT







GCTGCAATGGTTACCCTTGGATGTGGGCCTAATCT







ACCATCATTAGGGAATGTCCTGGGACAACTGAGTG







AATTCCAGGTCATTGTTAGGAAGACATCCAGCAAA







GCGGAAGAGATGGTCTTTGAAATTGTTAAGTATCC







GAGAATATTTCGGGGTCATACATTAATCCAGAAAG







GACTAGTCTGTGTCTCCGCAGAAAAATTTGTTAAG







TCACCAGGGAAAGTACAATCTGGAATGGACTATCT







CTTCATTCCGACATTTCTGTCAGTGACTTACTGTC







CAGCTGCAATCAAATTTCAGGTACCTGGCCCCATG







TTGAAAATGAGATCAAGATACACTCAGAGCTTACA







ACTTGAACTAATGATAAGAATCCTGTGTAAGCCCG







ATTCGCCACTTATGAAGGTCCATATCCCTGACAAG







GAAGGAAGAGGATGTCTTGTATCAGTATGGTTGCA







TGTATGCAATATCTTCAAATCAGGAAACAAGAATG







GCAGTGAGTGGCAGGAATACTGGATGAGAAAGTGT







GCTAACATGCAACTTGAAGTGTCGATTGCAGATAT







GTGGGGACCAACTATCATAATTCATGCCAGAGGTC







ACATTCCCAAAAGTGCTAAGTTGTTTTTTGGAAAG







GGTGGATGGAGCTGCCATCCACTTCACGAAGTTGT







TCCAAGTGTCACTAAAACACTATGGTCCGTGGGCT







GTGAGATTACAAAGGCGAAGGCAATAATACAAGAG







AGTAGCATCTCTCTTCTCGTGGAGACTACTGACAT







CATAAGTCCAAAAGTCAAAATTTCATCTAAGCATC







GCCGCTTTGGGAAATCAAATTGGGGTCTGTTCAAG







AAAACCAAATCACTGCCCAACCTGACGGAGCTGGA







ATGACTGACCCCCAATCGAGACTACACCACCTCAA







ACTATAGGTGGGTGGTACCTCAGTGATTAATCTCG







TAAGCACTGATCGTAGGCTACAACACACTAATATT







ATCCAGATTAGAGAGCTTAATTAGCTCTGTATTAA







TAATAACACTACTATTCCAATAACTGGAATCACCA







GCTTGATTTATCTCCAAAATGATTCAAAGAAAACA







AATCATATTAAGACTATCCTAAGCACGAACCCATA







TCGTCCTTCAAATCATGGGTACTATAATTCAATTT







CTGGTGGTCTCCTGTCTATTGGCAGGAGCAGGCAG







TCTTGATCCAGCAGCCCTCATGCAAATCGGTGTCA







TTCCAACAAATGTCCGGCAACTTATGTATTATACT







GAGGCCTCATCAGCATTCATTGTTGTGAAGTTAAT







GCCTACAATTGACTCGCCGATTAGTGGATGTAATA







TAACATCAATTTCAAGCTATAATGCAACAGTGACA







AAACTCCTACAGCCGATCGGTGAGAATTTGGAGAC







GATTAGGAACCAGTTGATTCCAACTCGGAGGAGAC







GCCGGTTTGCAGGGGTGGTGATTGGATTAGCTGCA







TTAGGAGTAGCTACTGCCGCACAGGTCACTGCCGC







AGTAGCACTAGTAAAGGCAAATGAAAATGCTGCGG







CTATACTCAATCTCAAAAATGCAATCCAAAAAACA







AATGCAGCAGTTGCAGATGTGGTCCAGGCCACACA







ATCACTAGGAACaGCAGTTCAAGCAGTTCAAGATC







ACATAAACAGTGTGGTAAGTCCAGCAATTACAGCA







GCCAATTGTAAAGCCCAAGATGCTATCATTGGCTC







AATCCTCAATCTCTATTTGACCGAGTTGACAACTA







TCTTCCACAATCAAATTACAAACCCTGCATTGAGT







CCTATTACAATTCAAGCTTTAAGGATCCTACTAGG







GAGTACCTTGCCGACTGTGGTCGAAAAATCTTTCA







ATACCCAGATAAGTGCGGCTGAGCTTCTCTCATCA







GGGTTATTGACAGGCCAGATTGTGGGATTAGATTT







GACCTATATGCAGATGGTCATAAAAATTGAGCTGC







CAACTTTAACTGTACAACCTGCAACCCAGATCATA







GATCTGGCCACCATTTCTGCATTCATTAACAATCA







AGAAGTCATGGCCCAATTACCAACACGTGTTATTG







TGACTGGCAGCTTGATCCAAGCCTATCCCGCATCG







CAATGCACTATTACACCCAACACTGTGTACTGTAG







GTATAATGATGCCCAAGTACTCTCAGATGATACGA







TGGCTTGCCTCCAAGGTAACTTGACAAGATGCACC







TTCTCTCCAGTGGTTGGGAGCTTTCTCACTCGATT







CGTGCTGTTCGATGGAATAGTTTATGCAAATTGCA







GGTCGATGTTGTGCAAGTGCATGCAGCCTGCTGCT







GTGATCCTACAGCCGAGTTCATCCCCTGTAACTGT







CATTGACATGTACAAATGTGTGAGTCTGCAGCTTG







ACAATCTCAGATTCACCATCACTCAATTGGCCAAT







GTAACCTACAATAGCACCATCAAGCTTGAAACATC







CCAGATCTTGCCTATTGATCCGTTGGATATATCCC







AGAATCTAGCTGCGGTGAATAAGAGTCTAAGTGAT







GCACTACAACACTTAGCACAAAGTGACACATACCT







TTCTGCAATCACATCAGCTACGACTACAAGTGTAT







TATCCATAATAGCAATCTGTCTTGGATCGTTAGGT







TTAATATTAATAATCTTGCTCAGTGTAGTTGTGTG







GAAGTTATTGACCATTGTCGCTGCTAATCGAAATA







GAATGGAGAATTTTGTTTATCATAATTCAGCATTC







CACCACTCACGATCTGATCTCAGTGAGAAAAATCA







ACCTGCAACTCTTGGAACAAGATAAGACAGTCATC







CATTAGTAATTTTTAAGAAAAAAACGATAGGACCG







AAACTAGTATTGAAAGAACCGTCTCGGTCAATCTA







GGTAATCGAGCTGcTACCGTCTCGGAAAGCTCAAA







TCATGCTGCCTGATCCGGAAGATCCGGAAAGCAAA







AAAGCTACAAGGAGAACAGGAAACCTAATTATCTG







CTTCCTATTCATCTTCTTTCCGTTTGTAAACTTCA







TTGTTCCAACTCTAAGACACTTGCTGTCCTAACAC







CTGCTATAGGCTATCCACTGCATCATCTCTTTTTA







AGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGC







GACTGCCGGTGCCAACAACACAATCCACAATCTAC







AGTCGACGCGGCCGCCatgttcgtcttcctggtcc







tgctgcctctggtctccATCcagtgcgtcaatctg







acaactcggactcagctgccacctgcttatactaa







tagcttcaccagaggcgtgtactatcctgacaagg







tgtttagaagctccgtgctgcactctacacaggat







ctgtttctgccattctttagcaacgtgacctggtt







ccacgccatccacgtgagcggcaccaatggcacaa







agcggttcgacaatcccgtgctgccttttaacgat







ggcgtgtacttcgcctctaccgagaagagcaacat







catcagaggctggatctttggcaccacactggact







ccaagacacagtctctgctgatcgtgaacaatgcc







accaacgtggtcatcaaggtgtgcgagttccagtt







ttgtaatgatcccttcctgggcgtgtactatcaca







agaacaataagagctgCatggagtccgagtttaga







gtgtattctagcgccaacaactgcacatttgagta







cgtgagccagcctttcctgatggacctggagggca







agcagggcaatttcaagaacctgagggagttcgtg







tttaagaatatcgacggctacttcaaaatctactc







taagcacacccccatcaacctggtgcgcgacctgc







ctcagggcttcagcgccctggagcccctggtggat







ctgcctatcggcatcaacatcacccggtttcagac







actgctggccctgcacagaagctacctgacacccg







gcgactcctctagcggatggaccgccggcgctgcc







gcctactatgtgggctacctccagccccggacctt







cctgctgaagtacaacgagaatggcaccatcacag







acgcagtggattgcgccctggaTcccctgagcgag







acaaagtgtacactgaagtcctttaccgtggagaa







gggcatctatcagacatccaatttcagggtgcagc







caaccgagtctatcgtgcgctttcctaatatcaca







aacctgtgcccatttggcgaggtgttcaacgcaac







ccgcttcgccagcgtgtacgcctggaataggaagc







ggatcagcaactgcgtggccgactatagcgtgctg







tacaactccgcctctttcagcacctttaagtgcta







tggcgtgtcccccacaaagctgaatgacctgtgct







ttaccaacgtctacgccgattctttcgtgatcagg







ggcgacgaggtgcgccagatcgcccccggccagac







aggcaagatcgcagactacaattataagctgccag







acgatttcaccggctgcgtgatcgcctggaacagc







aacaatctggattccaaagtgggcggcaactacaa







ttatcGgtaccggctgtttagaaagagcaatctga







agcccttcgagagggacatctctacagaaatctac







caggccggcagcaccccttgcaatggcgtggaggg







ctttaactgttatttcccactccagtcctacggct







tccagcccacaaacggcgtgggctatcagccttac







cgcgtggtggtgctgagctttgagctgctgcacgc







cccagcaacagtgtgcggccccaagaagtccacca







atctggtgaagaacaagtgcgtgaacttcaacttc







aacggcctgaccggcacaggcgtgctgaccgagtc







caacaagaagttcctgccatttcagcagttcggca







gggacatcgcagataccacagacgccgtgcgcgac







ccacagaccctggagatcctggacatcacaccctg







ctctttcggcggcgtgagcgtgatcacacccggca







ccaatacaagcaaccaggtggccgtgctgtatcag







gGcgtgaattgtaccgaggtgcccgtggctatcca







cgccgatcagctgaccccaacatggcgggtgtaca







gcaccggctccaacgtcttccagacaagagccgga







tgcctgatcggagcagagcacgtgaacaattccta







tgagtgcgacatcccaatcggcgccggcatctgtg







cctcttaccagacccagacaaactctcccagaaga







gcccggagcgtggcctcccagtctatcatcgccta







taccatgtccctgggcgccgagaacagcgtggcct







actctaacaatagcatcgccatcccaaccaacttc







acaatctctgtgaccacagagatcctgcccgtgtc







catgaccaagacatctgtggactgcacaatgtata







tctgtggcgattctaccgagtgcagcaacctgctg







ctccagtacggcagcttttgtacccagctgaatag







agccctgacaggcatcgccgtggagcaggataaga







acacacaggaggtgttcgcccaggtgaagcaaatc







tacaagaccccccctatcaaggactttggcggctt







caatttttcccagatcctgcctgatccatccaagc







cttctaagcggagctttatcgaggacctgctgttc







aacaaggtgaccctggccgatgccggcttcatcaa







gcagtatggcgattgcctgggcgacatcgcagcca







gggacctgatctgcgcccagaagtttaatggcctg







accgtgctgccacccctgctgacagatgagatgat







cgcacagtacacaagcgccctgctggccggcacca







tcacatccggatggaccttcggcgcaggagccgcc







ctccagatcccctttgccatgcagatggcctatag







gttcaacggcatcggcgtgacccagaatgtgctgt







acgagaaccagaagctgatcgccaatcagtttaac







tccgccatcggcaagatccaggacagcctgtcctc







tacagccagcgccctgggcaagctccaggatgtgg







tgaatcagaacgcccaggccctgaataccctggtg







aagcagctgagcagcaacttcggcgccatctctag







cgtgctgaatgacatcctgagccggctggacaagg







tggaggcagaggtgcagatcgaccggctgatcacc







ggccggctccagagcctccagacctatgtgacaca







gcagctgatcagggccgccgagatcagggccagcg







ccaatctggcagcaaccaagatgtccgagtgcgtg







ctgggccagtctaagagagtggacttttgtggcaa







gggctatcacctgatgtccttccctcagtctgccc







cacacggcgtggtgtttctgcacgtgacctacgtg







cccgcccaggagaagaacttcaccacagcccctgc







catctgccacgatggcaaggcccactttccaaggg







agggcgtgttcgtgtccaacggcacccactggttt







gtgacacagcgcaatttctacgagccccagatcat







caccacagacaacaccttcgtgagcggcaactgtg







acgtggtcatcggcatcgtgaacaataccgtgtat







gatccactccagcccgagctggacagctttaagga







ggagctggataagtatttcaagaatcacacctccc







ctgacgtggatctgggcgacatcagcggcatcaat







gcctccgtggtgaacatccagaaggagatcgaccg







cctgaacgaggtggctaagaatctgaacgagagcc







tgatcgacctccaggagctgggcaagtatgagcag







tacatcaagtggccctggtacatctggctgggctt







catcgccggcctgatcgccatcgtgatggtgacca







tcatgctgtgctgtatgacatcctgctgttcttgc







ctgaagggctgctgtagctgtggctcctgctgtAA







GTTATTGACCATTGTCGTTGCTAATCGAAATAGAA







TGGAGAATTTTGTTTATCATAAATGAacgcgtGCT







AGCCTCCTGCCATACTTCCTACTCACATCATATCT







ATTTTAAAGAAAAAATAGGCCCGAACACTAATCGT







GCCGGCAGTGCCACTGCACACACAACACTACACAT







ACAATACACTACAATGGTTGCAGAAGATGCCCCTG







TTAGGGGCACTTGCCGAGTATTATTTCGAACAACA







ACTTTAATTTTTCTATGCACACTATTAGCATTAAG







CATCTCTATCCTTTATGAGAGTTTAATAACCCAAA







AGCAAATCATGAGCCAAGCAGGCTCAACTGGATCT







AATTCTAGATTAGGAAGTATCACTGATCTTCTTAA







TAATATTCTCTCTGTCGCAAATCAGATTATATATA







ACTCTGCAGTCGCTCTACCTCTACAATTGGACACT







CTTGAATCAACACTCCTTACAGCCATTAAGTCTCT







TCAAACAAGTGACAAGCTAGAACAGAACTGCTCGT







GGGGTGCTGCACTGATTAATGATAATAGATACATT







AATGGCATCAATCAGTTCTATTTCTCAATTGCTGA







GGGTCGCAAGCTGACACTTGGCCCACTTCTTAATA







TACCTAGTTTCATTCCAACTGCCACGACACCAGAG







GGCTGCACCAGGATCCCATCATTCTCGCTCACCAA







GACACACTGGTGTTATACACACAATGTTATCCTGA







ATGGATGCCAGGATCATGTATCCTCAAATCAATTT







GTTTCCATGGGAATCATTGAACCCACTTCTGCCGG







GTTTCCATCCTTTCGAACCCTAAAGACTCTATATC







TCAGCGATGGGGTCAATCGTAAGAGCTGCTCTATC







AGTACAGTTCCGGGGGGTTGTATGATGTACTGTTT







CGTCTCTACTCAACCAGAGAGGGATGACTACTTTT







CTACCGCTCCTCCAGAACAACGAATTATTATAATG







TACTATAATGATACAATCGTGGAGCGCATAATTAA







TCCACCCGGGGTACTAGATGTATGGGCAACATTGA







ACCCAGGAACAGGAAGCGGGGTATATTATTTAGGT







TGGGTACTCTTTCCAATATATGGCGGCGTGATTAA







AGATACGAGTTTATGGAATAATCAAGCAAATAAAT







ACTTTATCCCCCAGATGGTTGCTGCTCTCTGCTCA







CAAAACCAGGCAACTCAAGTCCAAAATGCTAAGTC







ATCATACTATAGCAGCTGGTTTGGCAATCGAATGA







TTCAGTCTGGGATCCTGGCATGTCCTCTTCAACAG







GATCTAACCAATGAGTGTTTAGTTCTGCCCTTTTC







TAATGATCAGGTGCTTATGGGTGCTGAAGGGAGAT







TATACATGTATGGTGACTCGGTGTATTACTACCAA







AGAAGCAATAGTTGGTGGCCTATGACCATGCTGTA







TAAGGTAACCATAACATTCACTAATGGTCAGCCAT







CTGCTATATCAGCTCAGAATGTGCCCACACAGCAG







GTCCCTAGACCTGGGACAGGAAGCTGCTCTGCAAC







AAATAGATGTCCCGGTTTTTGCTTGAAAGGAGTGT







ATGCTGATGCCTGGTTACTGACCAACCCTTCGTCT







ACCAGTACATTTGGATCAGAAGCAACCTTCACTGG







TTCTTATCTCAACGCAGCAACTCAGCGTATCAATC







CGACGATGTATATCGCGAACAACACACAGATCATA







AGCTCACAGCAATTTGGATCAAGCGGTCAAGAAGC







AGCATATGGCCACACAACTTGTTTTAGGGACACAG







GCTCTGTTATGGTATACTGTATCTATATTATTGAA







TTGTCCTCATCTCTCTTAGGACAATTTCAGATTGT







CCCATTTATCCGTCAGGTGACACTATCCTAAAGGC







AGAAGCCTCCAGGTCTGACCCAGCCAATCAAAGCA







TTATACCAGACCATGGAATGCATACCAAACATTAT







TGACACTAATGACACACAAAATTGGTTTTAAGAAA







AACCAAGAGAACAATAGGCCAGAATGGCTGGGTCT







CGGGAGATATTACTCCCTGAAGTCCATCTCAATTC







ACCAATTGTAAAGCATAAGCTATACTATTACATTC







TACTTGGAAACCTCCCAAATGAGATCGACATTGAC







GATTTAGGTCCATTACATAATCAAAATTGGAATCA







AATAGCACATGAAGAGTCTAACTTAGCCCAACGCT







TGGTAAATGTAAGAAATTTTCTAATTACCCACATC







CCTGATCTTAGAAAGGGCCATTGGCAAGAGTATGT







CAATGTAATACTGTGGCCGCGAATTCTTCCCTTGA







TCCCGGATTTTAAAATCAATGACCAATTGCCTCTA







CTCAAAAATTGGGACAAGTTAGTTAAAGAATCATG







TTCAGTAATCAATGCGGGTACTTCCCAGTGCATTC







AGAATCTCAGCTATGGACTGACAGGTCGTGGGAAC







CTCTTTACACGATCACGTGAACTCTCTGGTGACCG







CAGGGATATTGATCTTAAGACGGTTGTGGCAGCAT







GGCATGACTCAGACTGGAAAAGAATAAGTGATTTT







TGGATTATGATCAAATTCCAGATGAGACAATTAAT







TGTTAGGCAAACAGATCATAATGATCCTGATTTAA







TCACGTATATCGAAAATAGAGAAGGCATAATCATC







ATAACCCCTGAACTGGTAGCATTATTTAACACTGA







GAATCATACACTAACATACATGACCTTTGAAATTG







TACTGATGGTTTCAGATATGTACGAAGGTCGTCAC







AACATTTTATCACTATGCACAGTTAGCACTTACCT







GAATCCTCTGAAGAAAAGAATAACATATTTATTGA







GCCTTGTAGATAACTTAGCTTTTCAGATAGGTGAT







GCTGTATATAACATAATTGCTTTGCTAGAATCCTT







TGTATATGCACAGTTGCAAATGTCAGATCCCATCC







CAGAACTCAGAGGACAATTCCATGCATTCGTATGT







TCTGAGATTCTTGATGCACTAAGGGGAACTAATAG







TTTCACCCAGGATGAATCAAGAACTGTGACAACCA







ATTTGATATCCCCATTCCAAGATCTGACCCCAGAT







CTTACGGCTGAATTGCTCTGTATAATGAGGCTTTG







GGGACACCCCATGCTCACCGCCAGTCAAGCTGCGG







GAAAGGTACGCGAGTCCATGTGTGCTGGAAAAGTA







TTAGACTTTCCCACCATTATGAAAACACTAGCCTT







TTTCCATACTATTCTGATCAATGGATACAGGAGGA







AGCATCATGGAGTATGGCCACCCTTAAACTTACCG







GGTAATGCTTCAAAGGGTCTCACGGAACTTATGAA







TGACAATACTGAGATAAGCTATGAATTCACACTTA







AGCATTGGAAGGAAATCTCTCTTATAAAATTCAAG







AAATGTTTTGATGCAGACGCAGGTGAGGAACTCAG







TATATTTATGAAAGATAAAGCAATTAGTGCCCCAA







AACAAGATTGGATGAGTGTGTTTAGAAGAAGCCTA







ATCAAACAGCGCCATCAGCATCATCAGGTCCCCCT







ACCAAATCCATTCAATCGACGGCTATTGCTAAACT







TTCTCGGAGATGACAAATTCGACCCGAATGTGGAG







CTACAGTATGTAACATCAGGTGAGTATCTACATGA







TGACACGTTTTGTGCATCATATTCACTAAAAGAGA







AGGAAATTAAACCTGATGGTCGAATTTTTGCAAAG







TTGACTAAGAGAATGAGATCATGTCAAGTTATAGC







AGAATCTCTTTTAGCGAACCATGCTGGGAAGTTAA







TGAAAGAGAATGGTGTTGTGATGAATCAGCTATCA







TTAACAAAATCACTATTAACAATGAGTCAGATTGG







AATAATATCCGAGAAAGCTAGAAAATCGACTCGAG







ATAACATAAATCAACCTGGTTTCCAGAATATCCAG







AGAAATAAATCACATCACTCCAAGCAAGTCAATCA







GCGAGATCCAAGTGATGACTTTGAATTGGCAGCAT







CTTTTTTAACTACTGATCTCAAAAAATATTGTTTA







CAATGGAGGTACCAGACAATTATCCCATTTGCTCA







ATCATTAAACAGAATGTATGGTTATCCTCATCTCT







TTGAGTGGATTCACTTACGGCTAATGCGTAGTACA







CTTTACGTGGGGGATCCCTTCAACCCACCAGCAGA







TACCAGTCAATTTGATCTAGATAAAGTAATTAATG







GAGATATCTTCATTGTATCACCCAGAGGTGGAATT







GAAGGGCTATGTCAAAAGGCTTGGACAATGATATC







TATCTCTGTGATAATTCTATCTGCCACAGAGTCTG







GCACACGAGTAATGAGTATGGTGCAGGGAGATAAT







CAAGCAATTGCTGTCACCACACGAGTACCAAGGAG







CCTGCCGACTCTTGAGAAAAAGACTATTGCTTTTA







GATCTTGTAATCTATTCTTTGAGAGGTTAAAATGT







AATAATTTTGGATTAGGTCACCATTTGAAAGAACA







AGAGACTATCATTAGTTCTCACTTCTTTGTTTATA







GCAAGAGAATATTCTATCAGGGGAGGATTCTAACG







CAAGCCTTAAAAAATGCTAGTAAGCTCTGCTTGAC







AGCTGATGTCCTAGGAGAATGTACCCAATCATCAT







GTTCTAATCTTGCAACTACTGTCATGAGGTTAACT







GAGAATGGTGTTGAAAAAGATATCTGTTTCTACTT







GAATATCTATATGACCATCAAACAGCTCTCCTATG







ATATCATCTTCCCTCAAGTGTCAATTCCTGGAGAT







CAGATCACATTAGAATACATAAATAATCCACACCT







GGTATCACGATTGGCTCTTCTGCCATCCCAGCTAG







GAGGTCTAAACTACCTGTCATGCAGTAGGCTGTTC







AATCGAAACATAGGCGACCCGGTGGTTTCCGCAGT







TGCAGATCTTAAGAGATTAATTAAATCAGGATGTA







TGGATTACTGGATCCTTTATAACTTATTAGGGAGA







AAACCGGGAAACGGCTCATGGGCTACTTTAGCAGC







TGACCCGTACTCAATCAATATAGAGTATCAATACC







CCCCAACTACAGCTCTTAAGAGGCACACCCAACAA







GCTCTGATGGAACTCAGTACGAATCCAATGTTACG







TGGCATATTCTCTGACAATGCACAGGCAGAAGAAA







ATAATCTTGCTAGATTTCTCCTGGATAGGGAGGTG







ATCTTTCCGCGTGTAGCTCACATCATCATTGAGCA







AACCAGTGTCGGGAGGAGAAAACAGATTCAAGGAT







ATTTGGATTCAACTAGATCGATAATGAGTAAATCA







CTAGAAATTAAGCCCTTGTCCAATAGGAAGCTTAA







TGAAATACTGGATTACAACATCAATTACCTAGCTT







ACAATTTGGCATTACTCAAGAATGCTATTGAACCT







CCGACTTATTTGAAAGCAATGACTCTTGAAACATG







TAGCATCGACATTGCAAGGAGCCTCCGGAAGCTCT







CCTGGGCCCCACTCTTGGGTGGGAGAAATCTTGAA







GGATTAGAGACGCCAGATCCCATTGAAATTACTGC







AGGAGCATTAATTGTTGGATCGGGCTACTGTGAAC







AGTGTGCTGCAGGAGACAATCGATTCACATGGTTT







TTCTTGCCATCTGGTATCGAGATAGGAGGGGATCC







CCGTGATAATCCTCCTATCCGTGTACCGTACATTG







GCTCCAGGACTGATGAGAGGAGGGTAGCCTCAATG







GCATACATCAGGGGTGCCTCGAGTAGCCTAAAAGC







AGTTCTTAGACTGGCGGGAGTGTACATCTGGGCAT







TCGGAGATACTCTGGAGAATTGGATAGATGCACTG







GATTTGTCTCACACTAGAGTTAACATCACACTTGA







ACAGCTGCAATCCCTCACCCCACTTCCAACCTCTG







CCAATCTAACCCATCGGTTGGATGATGGCACAACT







ACCCTAAAGTTTACTCCTGCGAGCTCTTACACCTT







TTCAAGTTTCACTCATATATCAAATGATGAGCAAT







ACCTGACAATTAATGACAAAACTGCAGATTCAAAT







ATAATCTACCAACAGTTAATGATCACTGGACTCGG







AATTTTAGAAACATGGAATAATCCCCCAATCAATA







GAACATTCGAAGAATCTACCCTACATTTGCACACT







GGTGCATCATGTTGTGTCCGACCTGTGGACTCCTG







CATCATCTCAGAAGCATTAACAGTCAAGCCACATA







TTACAGTACCGTACAGCAATAAATTTGTATTTGAT







GAAGACCCGCTATCTGAATATGAGACTGCAAAACT







GGAATCGTTATCATTTCAAGCCCAATTAGGCAACA







TTGATGCTGTAGATATGACAGGTAAATTAACATTA







TTGTCCCAATTCACTGCAAGGCAGATTATTAATGC







AATCACTGGACTCGATGAGTCTGTCTCTCTTACTA







ATGATGCCATTGTTGCATCAGACTATGTCTCCAAT







TGGATTAGTGAATGCATGTATACCAAATTAGATGA







ATTATTTATGTATTGTGGGTGGGAACTACTATTGG







AACTATCCTATCAAATGTATTATCTGAGGGTAGTT







GGGTGGAGTAATATAGTGGATTATTCTTACATGAT







CTTGAGAAGAATCCCGGGTGCAGCATTAAACAATC







TGGCATCTACATTAAGTCATCCAAAACTTTTCCGA







CGAGCTATCAACCTAGATATAGTTGCCCCCTTAAA







TGCTCCTCATTTTGCATCTCTGGACTACATCAAGA







TGAGTGTGGATGCAATACTCTGGGGCTGTAAAAGA







GTCATCAATGTGCTCTCCAATGGAGGGGACTTAGA







ATTAGTTGTGACATCTGAAGATAGCCTTATTCTCA







GTGACCGATCCATGAATCTCATTGCAAGGAAATTA







ACTTTATTATCACTGATTCACCATAATGGTTTGGA







ACTACCAAAGATTAAGGGGTTCTCTCCTGATGAGA







AGTGTTTCGCTTTGACAGAATTTTTGAGGAAAGTG







GTGAACTCAGGGTTGAGTTCAATAGAGAACCTATC







AAATTTTATGTACAATGTGGAGAACCCACGGCTTG







CAGCATTCGCCAGCAACAATTACTACCTGACCAGA







AAATTATTGAATTCAATACGAGATACTGAGTCGGG







TCAAGTAGCAGTCACCTCATATTATGAATCATTAG







AATATATTGATAGTCTTAAGCTAACCCCACATGTG







CCTGGTACCTCATGCATTGAGGATGATAGTCTATG







TACAAATGATTACATAATCTGGATCATAGAGTCTA







ATGCAAACTTGGAGAAGTATCCAATTCCAAATAGC







CCTGAGGATGATTCCAATTTCCATAACTTTAAGTT







GAATGCTCCATCGCACCATACCTTACGCCCATTAG







GGTTGTCATCAACTGCTTGGTATAAGGGTATAAGC







TGTTGCAGGTACCTTGAGCGATTAAAGCTACCACA







AGGTGATCATTTATATATTGCAGAAGGTAGTGGTG







CCAGTATGACAATCATAGAATACCTATTCCCAGGA







AGAAAGATATATTACAATTCTTTATTTAGTAGTGG







TGACAATCCCCCACAAAGAAATTATGCACCAATGC







CTACTCAGTTCATTGAGAGTGTCCCATACAAGCTC







TGGCAAGCACACACAGATCAATATCCCGAGATTTT







TGAGGACTTCATCCCTCTATGGAACGGAAATGCCG







CCATGACTGACATAGGAATGACAGCTTGTGTAGAA







TTCATCATCAATCGAGTCGGCCCAAGGACTTGCAG







TTTAGTACATGTAGATTTGGAATCAAGTGCAAGCT







TAAATCAACAATGCCTGTCAAAGCCGATAATTAAT







GCTATCATCACTGCTACAACTGTTTTGTGCCCTCA







TGGGGTGCTTATTCTGAAATATAGTTGGTTGCCAT







TTACTAGATTTAGTACTTTGATCACTTTCTTATGG







TGCTACTTTGAGAGAATCACTGTTCTTAGGAGCAC







ATATTCTGGTCCAGCTAATCATGAGGTTTATTTAA







TTTGTATCCTTGCCAACAACTTTGCATTCCAGACT







GTCTCGCAGGCAACAGGAATGGCGATGACTTTAAC







CGATCAAGGGTTTACTTTGATATCACCTGAAAGAA







TAAATCAGTATTGGGATGGTCACTTGAAGCAAGAA







CGTATCGTAGCAGAAGCAATTGATAAGGTGGTTCT







AGGAGAAGATGCTCTATTCAATTCGAGTGATAATG







AATTAATTCTCAAATGTGGAGGGACACCAAATGCA







CGGAATCTTATCGATATCGAGCCAGTCGCAACTTT







CATAGAATTTGAACAACTGATCTGCACAATGTTGA







CAACCCACTTGAAGGAAATAATTGATATAACAAGG







TCTGGAACCCAGGATTATGAAAGTTTATTACTCAC







TCCTTACAATTTAGGTCTTCTTGGTAAAATCAGTA







CGATAGTGAGATTATTAACAGAAAGGATTCTAAAT







CATACTATCAGGAATTGGTTGATCCTCCCACCTTC







GCTCCGGATGATCGTGAAGCAGGACTTGGAATTCG







GCATATTCAGGATTACTTCCATCCTCAATTCTGAT







CGGTTCCTGAAGCTTTCTCCAAATAGGAAATACTT







GATTACACAATTAACTGCAGGCTACATTAGGAAAT







TGATTGAGGGGGATTGTAATATCGATCTAACCAGA







CCTATCCAAAAACAAATCTGGAAAGCATTAGGTTG







TGTAGTCTATTGTCACGATCCAGTAGATCAAAGGG







AATCAACAGAGTTTATTGATATAAATATTAATGAA







GAAATAGACCGCGGGATCGATGGCGAGGAAATCTA







AATATATCAAGAATCAGAATTAGTTTAAGAAAAAA







GAAGAGGATTAATCTTGGTTTTCCCCTTGGT.






6. CVL52


The nucleic acid sequence for CVL52 is:










(SEQ ID NO: 66)



ACCAGGGGGAAAACGAAGTGGTGACTCAAATCATCGAAGACCCTCGAGATTACATAGG






TCCGGAACCTATGGCCTTCGTGACCGACCTCGAGTCAGAGTAGTTCAATAAGGACCTATCAAGTTTGG





GCAATTTTTCGTCCCCGACACAAAAATGTCATCCGTGCTTAAAGCATATGAGCGATTCACACTCACTC





AAGAACTGCAAGATCAGAGTGAGGAAGGTACAATCCCACCTACAACACTAAAACCGGTAATCAGGG





TATTTATACTAACCTCTAATAACCCAGAGCTAAGATCCCGGCTTCTTCTATTCTGCCTACGGATTGTTC





TCAGTAATGGTGCAAGGGATTCCCATCGCTTTGGAGCATTACTTACAATGTTTTCGCTACCATCAGCC





ACAATGCTCAATCATGTCAAATTAGCTGACCAGTCACCAGAAGCTGATATCGAAAGGGTAGAGATCG





ATGGCTTTGAGGAGGGATCATTCCGCTTAATCCCCAATGCTCGTTCAGGTATGAGCCGTGGAGAGATC





AATGCCTATGCTGCACTTGCAGAAGATCTACCTGACACACTAAACCATGCAACACCTTTTGTTGATTC





CGAAGTCGAGGGAACTGCATGGGATGAGATTGAGACTTTCTTAGATATGTGTTACAGTGTCCTAATGC





AGGCATGGATAGTGACTTGCAAGTGCATGACTGCGCCAGACCAACCTGCTGCTTCTATTGAGAAACG





CCTGCAAAAATATCGTCAGCAAGGCAGGATCAACCCGAGATATCTCCTGCAACCGGAGGCTCGAAGA





ATAATCCAGAATGTAATCCGAAAGGGAATGGTGGTCAGACATTTCCTCACCTTTGAACTGCAGCTTGC





CCGAGCACAAAGCCTTGTATCAAATAGGTATTATGCTATGGTAGGGGATGTTGGAAAGTATATAGAG





AATTGTGGAATGGGAGGCTTCTTTTTGACACTAAAATATGCATTAGGAACCAGATGGCCCACACTTGC





TTTAGCTGCATTTTCAGGAGAGCTAACAAAGCTAAAGTCCCTCATGGCATTATACCAGACCCTTGGTG





AGCAGGCCCGATATTTGGCCCTATTGGAGTCACCACATTTGATGGATTTTGCTGCAGCAAACTACCCA





CTGCTATATAGCTATGCTATGGGAATAGGCTATGTGTTAGATGTCAACATGAGGAACTACGCTTTCTC





CAGATCATACATGAATAAGACATATTTCCAATTGGGAATGGAAACTGCAAGAAAACAACAGGGTGCA





GTTGACATGAGGATGGCAGAAGATCTCGGTCTAACTCAAGCCGAACGCACCGAGATGGCAAATACAC





TTGCCAAATTGACCACAGCAAATCGAGGGGCAGACACCAGGGGAGGAGTCAACCCGTTCTCATCTAT





CACTGGGACAACTCAGGTGCCCGCTGCAGCAACAGGTGACACATTCGAGAGTTACATGGCAGCGGAT





CGACTGAGGCAGAGATATGCTGATGCAGGCACCCACGATGATGAGATGCCACCATTGGAAGAGGAG





GAAGAGGACGACACATCTGCAGGTCCACGCACTGGACTAACTCTTGAACAAGTGGCCTTGGACATCC





AGAACGCAGCAGTTGGAGCTCCCATCCATACAGATGACCTGAATGCCGCACTGGGTGATCTTGACAT





CTAGACAATTCAGATCCCAATCTTAAATCGACACACCTAATTGACCAGTTAGATGGAACTACAGTGG





ATTCCATAAGGTTCCTGCCTACCATCGGCTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAA





GCGACTGCCGATGCCAATAACACAATCCACAATCTACAATGGATCCCACTGATCTGAGCTTCTCCCCA





GATGAGATCAATAAGCTCATAGAGACAGGCCTGAATACTGTGGAGTATTTTACTTCCCAACAAGTCA





CAGGAACATCCTCTCTTGGAAAGAATACAATACCACCAGGGGTCACAGGACTACTAACCAATGCTGC





AGAGGCAAAGATCCAAGAGTCAACCAACCATCAGAAGGGTTCAGTTGGTGGGGGCGCAAAACCAAA





GAAACCGCGACCAAAAATTGCCATTGTGCCAGCAGATGACAAAACGGTGCCCGGAAAGCCGATCCC





AAACCCTCTATTAGGTCTGGACTCCACCCCGAGCACCCAAACTGTGCTTGATCTAAGTGGGAAAACAT





TACCATCAGGATCCTATAAGGGGGTTAAACTTGCGAAATTTGGAAAAGAAAATCTGATGACACGGTT





CATCGAGGAACCCAGAGAGAATCCTATCGCAACCAATTCCCCCATCGATTTTAAGAGGGGCAGGGAT





ACCGGCGGGTTCCATAGAAGGGAGTACTCAATCGGATGGGTGGGAGATGAAGTCAAGGTCACTGAGT





GGTGCAATCCATCCTGTTCTCCAATCACCGCTGCAGCAAGGCGATTTGAATGCACTTGTCACCAGTGT





CCAGTCACTTGCTCTGAATGTGAACGAGATACTTAATACAGTGAGAAATTTGGACTCTCGGATGAATC





AACTGGAGACAAAAGTAGATCGCATTCTCTCATCTCAGTCTCTAATCCAGACCATCAAGAATGACAT





AGTTGGACTTAAAGCAGGGATGGCTACTTTAGAAGGAATGATTACAACTGTGAAAATCATGGACCCG





GGAGTTCCCAGTAATGTTACTGTGGAAGATGTACGCAAGAAACTAAGTAACCATGCTGTTGTTGTGCC





AGAATCATTCAATGATAGTTTCTTGACTCAATCTGAAGATGTAATTTCACTTGATGAGTTGGCTCGAC





CAACTGCAACAAGTGTTAAGAAGATTGTCAGGAAGGTTCCTCCTCAGAAGGATCTGACTGGATTGAA





GATCACACTAGAGCAATTGGCAAAGGATTGCATCAGCAAACCGAAGATGAGGGAAGAGTATCTCCTC





AAAATCAACCAGGCTTCCAGTGAGGCTCAGCTAATTGACCTCAAGAAAGCAATCATCCGCAGTGCAA





TTTGATCAAGAAACACCCAATTACACTACACTGGTATGACACTGTACTAACCCTGAGGGTTTTAGAAA





AAACGATTAACGATAAATAAGCCCGAACACTACACACCACCCGAGGCAGCCATGCCATCCATCAGCA





TCCCCGCAGACCCCACCAATCCACGTCAATCAATAAAAGCGTTCCCAATTGTGATCAACCGTGATGG





GGGTGAGAAAGGTCGCTTGGTTAAACAACTACGCACAACCTACTTGAATGACCTAGATACTCATGAG





CCACTGGTGACATTCGTAAATACTTATGGATTCATCTACGAACAGGATCGGGGAAATACCATTGTCGG





AGAGGATCAACATGGGAAGAAAAGAGAGGCTGTGACTGCTGCAATGGTTACCCTTGGATGTGGGCCT





AATCTACCATCATTAGGGAATGTCCTGGGACAACTGAGTGAATTCCAGGTCATTGTTAGGAAGACAT





CCAGCAAAGCGGAAGAGATGGTCTTTGAAATTGTTAAGTATCCGAGAATATTTCGGGGTCATACATT





AATCCAGAAAGGACTAGTCTGTGTCTCCGCAGAAAAATTTGTTAAGTCACCAGGGAAAGTACAATCT





GGAATGGACTATCTCTTCATTCCGACATTTCTGTCAGTGACTTACTGTCCAGCTGCAATCAAATTTCAG





GTACCTGGCCCCATGTTGAAAATGAGATCAAGATACACTCAGAGCTTACAACTTGAACTAATGATAA





GAATCCTGTGTAAGCCCGATTCGCCACTTATGAAGGTCCATATCCCTGACAAGGAAGGAAGAGGATG





TCTTGTATCAGTATGGTTGCATGTATGCAATATCTTCAAATCAGGAAACAAGAATGGCAGTGAGTGGC





AGGAATACTGGATGAGAAAGTGTGCTAACATGCAACTTGAAGTGTCGATTGCAGATATGTGGGGACC





AACTATCATAATTCATGCCAGAGGTCACATTCCCAAAAGTGCTAAGTTGTTTTTTGGAAAGGGTGGAT





GGAGCTGCCATCCACTTCACGAAGTTGTTCCAAGTGTCACTAAAACACTATGGTCCGTGGGCTGTGAG





ATTACAAAGGCGAAGGCAATAATACAAGAGAGTAGCATCTCTCTTCTCGTGGAGACTACTGACATCA





TAAGTCCAAAAGTCAAAATTTCATCTAAGCATCGCCGCTTTGGGAAATCAAATTGGGGTCTGTTCAAG





AAAACCAAATCACTGCCCAACCTGACGGAGCTGGAATGACTGACCCCCAATCGAGACTACACCACCT





CAAACTATAGGTGGGTGGTACCTCAGTGATTAATCTCGTAAGCACTGATCGTAGGCTACAACACACT





AATATTATCCAGATTAGAGAGCTTAATTAGCTCTGTATTAATAATAACACTACTATTCCAATAACTGG





AATCACCAGCTTGATTTATCTCCAAAATGATTCAAAGAAAACAAATCATATTAAGACTATCCTAAGCA





CGAACCCATATCGTCCTTCAAATCATGGGTACTATAATTCAATTTCTGGTGGTCTCCTGTCTATTGGCA





GGAGCAGGCAGTCTTGATCCAGCAGCCCTCATGCAAATCGGTGTCATTCCAACAAATGTCCGGCAAC





TTATGTATTATACTGAGGCCTCATCAGCATTCATTGTTGTGAAGTTAATGCCTACAATTGACTCGCCG





ATTAGTGGATGTAATATAACATCAATTTCAAGCTATAATGCAACAGTGACAAAACTCCTACAGCCGA





TCGGTGAGAATTTGGAGACGATTAGGAACCAGTTGATTCCAACTCGGAGGAGACGCCGGTTTGCAGG





GGTGGTGATTGGATTAGCTGCATTAGGAGTAGCTACTGCCGCACAGGTCACTGCCGCAGTAGCACTA





GTAAAGGCAAATGAAAATGCTGCGGCTATACTCAATCTCAAAAATGCAATCCAAAAAACAAATGCAG





CAGTTGCAGATGTGGTCCAGGCCACACAATCACTAGGAACaGCAGTTCAAGCAGTTCAAGATCACAT





AAACAGTGTGGTAAGTCCAGCAATTACAGCAGCCAATTGTAAAGCCCAAGATGCTATCATTGGCTCA





ATCCTCAATCTCTATTTGACCGAGTTGACAACTATCTTCCACAATCAAATTACAAACCCTGCATTGAG





TCCTATTACAATTCAAGCTTTAAGGATCCTACTAGGGAGTACCTTGCCGACTGTGGTCGAAAAATCTT





TCAATACCCAGATAAGTGCGGCTGAGCTTCTCTCATCAGGGTTATTGACAGGCCAGATTGTGGGATTA





GATTTGACCTATATGCAGATGGTCATAAAAATTGAGCTGCCAACTTTAACTGTACAACCTGCAACCCA





GATCATAGATCTGGCCACCATTTCTGCATTCATTAACAATCAAGAAGTCATGGCCCAATTACCAACAC





GTGTTATTGTGACTGGCAGCTTGATCCAAGCCTATCCCGCATCGCAATGCACTATTACACCCAACACT





GTGTACTGTAGGTATAATGATGCCCAAGTACTCTCAGATGATACGATGGCTTGCCTCCAAGGTAACTT





GACAAGATGCACCTTCTCTCCAGTGGTTGGGAGCTTTCTCACTCGATTCGTGCTGTTCGATGGAATAG





TTTATGCAAATTGCAGGTCGATGTTGTGCAAGTGCATGCAGCCTGCTGCTGTGATCCTACAGCCGAGT





TCATCCCCTGTAACTGTCATTGACATGTACAAATGTGTGAGTCTGCAGCTTGACAATCTCAGATTCAC





CATCACTCAATTGGCCAATGTAACCTACAATAGCACCATCAAGCTTGAAACATCCCAGATCTTGCCTA





TTGATCCGTTGGATATATCCCAGAATCTAGCTGCGGTGAATAAGAGTCTAAGTGATGCACTACAACAC





TTAGCACAAAGTGACACATACCTTTCTGCAATCACATCAGCTACGACTACAAGTGTATTATCCATAAT





AGCAATCTGTCTTGGATCGTTAGGTTTAATATTAATAATCTTGCTCAGTGTAGTTGTGTGGAAGTTATT





GACCATTGTCGCTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAATTCAGCATTCCACCACT





CACGATCTGATCTCAGTGAGAAAAATCAACCTGCAACTCTTGGAACAAGATAAGACAGTCATCCATT





AGTAATTTTTAAGAAAAAAACGATAGGACCGAAACTAGTATTGAAAGAACCGTCTCGGTCAATCTAG





GTAATCGAGCTGcTACCGTCTCGGAAAGCTCAAATCGCGCGCCACCatgtcagataacggaccacaga






accagaggaacgcacccaggattactttcggaggaccaagcgatagcaccgggagcaaccagaatgg







agagcggagcggagcaagatccaagcagagacggccccagggcctgccaaacaataccgcatcct







ggttcaccgccctgacacagcacggcaaggaggacctgaagtttccaaggggacagggagtgccta







tcaacaccaatagctcccctgacgatcagatcggctactataggagggcaacaaggagaatcaggg







gaggcgacggcaagatgaaggatctgagcccacgctggtacttctactatctgggaaccggacc







tgaggcaggcctgccatatggcgccaacaaggacggaatcatctgggtggcaaccgagggcgccctg







aacacaccaaaggatcacatcggcacaagaaatcccgccaacaatgcagcaatcgtgctgcagc







tgccacagggaaccacactgcccaagggcttttacgcagagggctctcggggaggcagccaggcatct







agcagatcctctagccggagcagaaactcctctaggaattccaccccaggaagctccaggggcacatcc







cctgcccgcatggcaggaaacggaggcgacgccgccctggccctgctgctgctggatcgcctgaatcag







ctggagtccaagatgtctggcaagggacagcagcagcagggacagaccgtgacaaagaagtccgccgc







cgaggcctctaagaagccaaggcagaagcgcaccgccacaaaggcctacaacgtgacccaggcctt







cggcaggcgcggaccagagcagacacagggcaattttggcgaccaggagctgatcaggcaggga







accgattataagcactggcctcagatcgcccagttcgccccatctgccagcgccttctttggcatgtcta







gaatcggcatggaggtgacccccagcggcacatggctgacctacacaggcgccatcaagctggac







gataaggaccctaacttcaaggatcaggtcatcctgctgaacaagcacatcgacgcctataagaccttt







ccccctacagagcccaagaaggacaagaagaagaaggccgatgagacacaggccctgcctcagaggcagaa







gaagcagcagaccgtgacactgctgccagccgccgatctggacgatttctccaaacagctgcagcagag







catgtccagtgccgactccacccaggcttgaCGTACGACCTGCTATAGGCTATCCACTGCATCATCTC






TTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCCGGTGCCAACAACACAATCC





ACAATCTACAGTCGACGCGGCCGCCACCatgttcgtgttcctggtgctgctgccactggtcagcagccagtgc





gtgaatttcactacccggacccagctgcctcctgcttatacaaacagcttcaccaggggagtgtactac





cccgataaggtgttccgcagctctgtgctgcacagcacccaggacttgtttcttcccttcttcagcaac





gtgacctggttccacgccatccacgtgtccggcaccaacggcaccaaaagattcgccaatcctgtgctgcctt





tcaacgatggcgtgtactttgcctctacagagaagtctaacatcatcagaggctggatcttcggcacaaccc





tggattctaaaacccagagcctgctgatcgtgaacaatgccaccaatgtagtgatcaaggtttgtgagtt





ccagttctgcaacgacccctttctgggcgtttactaccacaagaacaacaaaagctggatggaaagcgag





ttcagggtgtactctagcgccaacaactgtaccttcgagtacgtgagccagccttttctgatggacct





ggagggcaagcagggcaacttcaaaaacctgcgggagttcgtgtttaagaacatcgacggatacttcaag





atttactccaagcacaccccaattaacttggttagaggactgccccaaggcttcagcgccctggaaccc





ctggtggacctgcctatcggcatcaacatcacaagattccaaaccctgcatagaagctatctgacacca





ggcgactctagctctggatggacagccggcgccgctgcttattacgtgggctacctgcagcctagaacctt





cctcctgaaatacaacgagaacggaaccatcaccgacgccgtggactgcgccctggatcctctgagcgagac





aaagtgcaccctgaagtccttcaccgtcgaaaagggcatctaccaaacaagcaacttcagagtgcagcctact





gagagcatcgtgcggtttccaaacatcaccaacctgtgtccttttggcgaggtgttcaacgccacccggttc





gcttccgtgtacgcctggaatagaaagcggatcagcaactgcgtggccgactacagcgtgctgtataat





agcgcctcattttctacttttaaatgttacggcgtgtctcctacaaagctgaacgatctgtgctt





cacaaatgtgtacgccgatagcttcgtgattagaggcgacgaggtgcggcagatcgcccctggcca





gaccggcaacatcgctgactacaactacaagctgcctgacgacttcaccggctgtgtgatcgcat





ggaacagcaataacctggactctaaggtgggcggaaactacaattacctgtacagactgttcag





aaagagcaacctgaagcccttcgagagagatatctccacagaaatctatcaggccggatctacacc





ttgtaatggcgtgaagggcttcaactgctacttccctctgcaatcctacggctttcagcccacatacggcg





tgggctaccagccataccgggtcgtggtgctgagcttcgagctgctgcacgcccctgccacagtgtgc





ggccctaagaagagcaccaatctggtaaagaacaagtgcgtcaacttcaatttcaacggcctgaccg





ggaccggagtgctgaccgaaagcaacaagaaattcctgccgttccagcagttcggcagagatatcgc





cgacaccaccgatgccgtgcgggacccccagacacttgaaatcctggacatcaccccttgcagt





tttggcggcgtgtccgtgatcacacctggaacaaacaccagcaaccaggtggccgtgctgtaccagg





gcgtcaactgcaccgaggtccccgtggccatccacgccgatcagctgacacctacatggcgggtgtact





ctaccggcagcaacgtgttccaaaccagagccggctgcctgatcggcgctgagcacgtgaacaacagc





tacgagtgcgacattcctatcggtgctggcatctgcgcctcttaccagacacagacaaacagc





cccagaagagcgagaagcgtggctagtcagagcatcatcgcctacaccatgagcctgggcgt





ggagaacagcgtggcctactctaacaatagcatcgccatcccaaccaacttcacaatctctgtg





accacagagatcctgcccgtgtccatgaccaagacatctgtggactgcacaatgtatatctgtggcg





attctaccgagtgcagcaacctgctgctccagtacggcagcttttgtacccagctgaataga





gccctgacaggcatcgccgtggagcaggataagaacacacaggaggtgttcgcccaggtgaag





caaatctacaagaccccccctatcaaggactttggcggcttcaatttttcccagatcctgcctgatc





catccaagccttctaagcggagctttatcgaggacctgctgttcaacaaggtgaccctggccg





atgccggcttcatcaagcagtatggcgattgcctgggcgacatcgcagccagggacctgatctgcg





cccagaagtttaatggcctgaccgtgctgccacccctgctgacagatgagatgatcgcacagtac





acaagcgccctgctggccggcaccatcacatccggatggaccttcggcgcaggagccgccctccagat





cccctttgccatgcagatggcctataggttcaacggcatcggcgtgacccagaatgtgctgtacg





agaaccagaagctgatcgccaatcagtttaactccgccatcggcaagatccaggacagcctgtc





ctctacagccagcgccctgggcaagctccaggatgtggtgaatcagaacgcccaggccctgaatac





cctggtgaagcagctgagcagcaacttcggcgccatctctagcgtgctgaatgacatcctgagcc





ggctggacaaggtggaggcagaggtgcagatcgaccggctgatcaccggccggctccagagcctc





cagacctatgtgacacagcagctgatcagggccgccgagatcagggccagcgccaatctggcagc





aaccaagatgtccgagtgcgtgctgggccagtctaagagagtggacttttgtggcaagggctatca





cctgatgtccttccctcagtctgccccacacggcgtggtgtttctgcacgtgacctacgtgcccgccc





aggagaagaacttcaccacagcccctgccatctgccacgatggcaaggcccactttccaagggag





ggcgtgttcgtgtccaacggcacccactggtttgtgacacagcgcaatttctacgagccccaga





tcatcaccacagacaacaccttcgtgagcggcaactgtgacgtggtcatcggcatcgtgaacaata





ccgtgtatgatccactccagcccgagctggacagctttaaggaggagctggataagtatttcaag





aatcacacctcccctgacgtggatctgggcgacatcagcggcatcaatgcctccgtggtgaacatcc





agaaggagatcgaccgcctgaacgaggtggctaagaatctgaacgagagcctgatcgacctccag





gagctgggcaagtatgagcagtacatcaagtggccctggtacatctggctgggcttcatcgccggcctgatcgc





catcgtgatggtgaccatcatgctgtgctgtatgacatcctgctgttcttgcctgaagggctgctgtag





ctgtggctcctgctgtAAGTTATTGACCATTGTCGTTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAA





ATGAACGCGTGCTAGCCTCCTGCCATACTTCCTACTCACATCATATCTATTTTAAAGAAAAAATAGGC





CCGAACACTAATCGTGCCGGCAGTGCCACTGCACACACAACACTACACATACAATACACTACAATGG





TTGCAGAAGATGCCCCTGTTAGGGGCACTTGCCGAGTATTATTTCGAACAACAACTTTAATTTTTCTA





TGCACACTATTAGCATTAAGCATCTCTATCCTTTATGAGAGTTTAATAACCCAAAAGCAAATCATGAG





CCAAGCAGGCTCAACTGGATCTAATTCTAGATTAGGAAGTATCACTGATCTTCTTAATAATATTCTCT





CTGTCGCAAATCAGATTATATATAACTCTGCAGTCGCTCTACCTCTACAATTGGACACTCTTGAATCA





ACACTCCTTACAGCCATTAAGTCTCTTCAAACAAGTGACAAGCTAGAACAGAACTGCTCGTGGGGTG





CTGCACTGATTAATGATAATAGATACATTAATGGCATCAATCAGTTCTATTTCTCAATTGCTGAGGGT





CGCAAGCTGACACTTGGCCCACTTCTTAATATACCTAGTTTCATTCCAACTGCCACGACACCAGAGGG





CTGCACCAGGATCCCATCATTCTCGCTCACCAAGACACACTGGTGTTATACACACAATGTTATCCTGA





ATGGATGCCAGGATCATGTATCCTCAAATCAATTTGTTTCCATGGGAATCATTGAACCCACTTCTGCC





GGGTTTCCATCCTTTCGAACCCTAAAGACTCTATATCTCAGCGATGGGGTCAATCGTAAGAGCTGCTC





TATCAGTACAGTTCCGGGGGGTTGTATGATGTACTGTTTCGTCTCTACTCAACCAGAGAGGGATGACT





ACTTTTCTACCGCTCCTCCAGAACAACGAATTATTATAATGTACTATAATGATACAATCGTGGAGCGC





ATAATTAATCCACCCGGGGTACTAGATGTATGGGCAACATTGAACCCAGGAACAGGAAGCGGGGTAT





ATTATTTAGGTTGGGTACTCTTTCCAATATATGGCGGCGTGATTAAAGATACGAGTTTATGGAATAAT





CAAGCAAATAAATACTTTATCCCCCAGATGGTTGCTGCTCTCTGCTCACAAAACCAGGCAACTCAAGT





CCAAAATGCTAAGTCATCATACTATAGCAGCTGGTTTGGCAATCGAATGATTCAGTCTGGGATCCTGG





CATGTCCTCTTCAACAGGATCTAACCAATGAGTGTTTAGTTCTGCCCTTTTCTAATGATCAGGTGCTTA





TGGGTGCTGAAGGGAGATTATACATGTATGGTGACTCGGTGTATTACTACCAAAGAAGCAATAGTTG





GTGGCCTATGACCATGCTGTATAAGGTAACCATAACATTCACTAATGGTCAGCCATCTGCTATATCAG





CTCAGAATGTGCCCACACAGCAGGTCCCTAGACCTGGGACAGGAAGCTGCTCTGCAACAAATAGATG





TCCCGGTTTTTGCTTGAAAGGAGTGTATGCTGATGCCTGGTTACTGACCAACCCTTCGTCTACCAGTA





CATTTGGATCAGAAGCAACCTTCACTGGTTCTTATCTCAACGCAGCAACTCAGCGTATCAATCCGACG





ATGTATATCGCGAACAACACACAGATCATAAGCTCACAGCAATTTGGATCAAGCGGTCAAGAAGCAG





CATATGGCCACACAACTTGTTTTAGGGACACAGGCTCTGTTATGGTATACTGTATCTATATTATTGAA





TTGTCCTCATCTCTCTTAGGACAATTTCAGATTGTCCCATTTATCCGTCAGGTGACACTATCCTAAAGG





CAGAAGCCTCCAGGTCTGACCCAGCCAATCAAAGCATTATACCAGACCATGGAATGCATACCAAACA





TTATTGACACTAATGACACACAAAATTGGTTTTAAGAAAAACCAAGAGAACAATAGGCCAGAATGGC





TGGGTCTCGGGAGATATTACTCCCTGAAGTCCATCTCAATTCACCAATTGTAAAGCATAAGCTATACT





ATTACATTCTACTTGGAAACCTCCCAAATGAGATCGACATTGACGATTTAGGTCCATTACATAATCAA





AATTGGAATCAAATAGCACATGAAGAGTCTAACTTAGCCCAACGCTTGGTAAATGTAAGAAATTTTC





TAATTACCCACATCCCTGATCTTAGAAAGGGCCATTGGCAAGAGTATGTCAATGTAATACTGTGGCCG





CGAATTCTTCCCTTGATCCCGGATTTTAAAATCAATGACCAATTGCCTCTACTCAAAAATTGGGACAA





GTTAGTTAAAGAATCATGTTCAGTAATCAATGCGGGTACTTCCCAGTGCATTCAGAATCTCAGCTATG





GACTGACAGGTCGTGGGAACCTCTTTACACGATCACGTGAACTCTCTGGTGACCGCAGGGATATTGAT





CTTAAGACGGTTGTGGCAGCATGGCATGACTCAGACTGGAAAAGAATAAGTGATTTTTGGATTATGA





TCAAATTCCAGATGAGACAATTAATTGTTAGGCAAACAGATCATAATGATCCTGATTTAATCACGTAT





ATCGAAAATAGAGAAGGCATAATCATCATAACCCCTGAACTGGTAGCATTATTTAACACTGAGAATC





ATACACTAACATACATGACCTTTGAAATTGTACTGATGGTTTCAGATATGTACGAAGGTCGTCACAAC





ATTTTATCACTATGCACAGTTAGCACTTACCTGAATCCTCTGAAGAAAAGAATAACATATTTATTGAG





CCTTGTAGATAACTTAGCTTTTCAGATAGGTGATGCTGTATATAACATAATTGCTTTGCTAGAATCCTT





TGTATATGCACAGTTGCAAATGTCAGATCCCATCCCAGAACTCAGAGGACAATTCCATGCATTCGTAT





GTTCTGAGATTCTTGATGCACTAAGGGGAACTAATAGTTTCACCCAGGATGAATCAAGAACTGTGAC





AACCAATTTGATATCCCCATTCCAAGATCTGACCCCAGATCTTACGGCTGAATTGCTCTGTATAATGA





GGCTTTGGGGACACCCCATGCTCACCGCCAGTCAAGCTGCGGGAAAGGTACGCGAGTCCATGTGTGC





TGGAAAAGTATTAGACTTTCCCACCATTATGAAAACACTAGCCTTTTTCCATACTATTCTGATCAATG





GATACAGGAGGAAGCATCATGGAGTATGGCCACCCTTAAACTTACCGGGTAATGCTTCAAAGGGTCT





CACGGAACTTATGAATGACAATACTGAGATAAGCTATGAATTCACACTTAAGCATTGGAAGGAAATC





TCTCTTATAAAATTCAAGAAATGTTTTGATGCAGACGCAGGTGAGGAACTCAGTATATTTATGAAAGA





TAAAGCAATTAGTGCCCCAAAACAAGATTGGATGAGTGTGTTTAGAAGAAGCCTAATCAAACAGCGC





CATCAGCATCATCAGGTCCCCCTACCAAATCCATTCAATCGACGGCTATTGCTAAACTTTCTCGGAGA





TGACAAATTCGACCCGAATGTGGAGCTACAGTATGTAACATCAGGTGAGTATCTACATGATGACACG





TTTTGTGCATCATATTCACTAAAAGAGAAGGAAATTAAACCTGATGGTCGAATTTTTGCAAAGTTGAC





TAAGAGAATGAGATCATGTCAAGTTATAGCAGAATCTCTTTTAGCGAACCATGCTGGGAAGTTAATG





AAAGAGAATGGTGTTGTGATGAATCAGCTATCATTAACAAAATCACTATTAACAATGAGTCAGATTG





GAATAATATCCGAGAAAGCTAGAAAATCGACTCGAGATAACATAAATCAACCTGGTTTCCAGAATAT





CCAGAGAAATAAATCACATCACTCCAAGCAAGTCAATCAGCGAGATCCAAGTGATGACTTTGAATTG





GCAGCATCTTTTTTAACTACTGATCTCAAAAAATATTGTTTACAATGGAGGTACCAGACAATTATCCC





ATTTGCTCAATCATTAAACAGAATGTATGGTTATCCTCATCTCTTTGAGTGGATTCACTTACGGCTAAT





GCGTAGTACACTTTACGTGGGGGATCCCTTCAACCCACCAGCAGATACCAGTCAATTTGATCTAGATA





AAGTAATTAATGGAGATATCTTCATTGTATCACCCAGAGGTGGAATTGAAGGGCTATGTCAAAAGGC





TTGGACAATGATATCTATCTCTGTGATAATTCTATCTGCCACAGAGTCTGGCACACGAGTAATGAGTA





TGGTGCAGGGAGATAATCAAGCAATTGCTGTCACCACACGAGTACCAAGGAGCCTGCCGACTCTTGA





GAAAAAGACTATTGCTTTTAGATCTTGTAATCTATTCTTTGAGAGGTTAAAATGTAATAATTTTGGATT





AGGTCACCATTTGAAAGAACAAGAGACTATCATTAGTTCTCACTTCTTTGTTTATAGCAAGAGAATAT





TCTATCAGGGGAGGATTCTAACGCAAGCCTTAAAAAATGCTAGTAAGCTCTGCTTGACAGCTGATGTC





CTAGGAGAATGTACCCAATCATCATGTTCTAATCTTGCAACTACTGTCATGAGGTTAACTGAGAATGG





TGTTGAAAAAGATATCTGTTTCTACTTGAATATCTATATGACCATCAAACAGCTCTCCTATGATATCAT





CTTCCCTCAAGTGTCAATTCCTGGAGATCAGATCACATTAGAATACATAAATAATCCACACCTGGTAT





CACGATTGGCTCTTCTGCCATCCCAGCTAGGAGGTCTAAACTACCTGTCATGCAGTAGGCTGTTCAAT





CGAAACATAGGCGACCCGGTGGTTTCCGCAGTTGCAGATCTTAAGAGATTAATTAAATCAGGATGTA





TGGATTACTGGATCCTTTATAACTTATTAGGGAGAAAACCGGGAAACGGCTCATGGGCTACTTTAGCA





GCTGACCCGTACTCAATCAATATAGAGTATCAATACCCCCCAACTACAGCTCTTAAGAGGCACACCC





AACAAGCTCTGATGGAACTCAGTACGAATCCAATGTTACGTGGCATATTCTCTGACAATGCACAGGC





AGAAGAAAATAATCTTGCTAGATTTCTCCTGGATAGGGAGGTGATCTTTCCGCGTGTAGCTCACATCA





TCATTGAGCAAACCAGTGTCGGGAGGAGAAAACAGATTCAAGGATATTTGGATTCAACTAGATCGAT





AATGAGTAAATCACTAGAAATTAAGCCCTTGTCCAATAGGAAGCTTAATGAAATACTGGATTACAAC





ATCAATTACCTAGCTTACAATTTGGCATTACTCAAGAATGCTATTGAACCTCCGACTTATTTGAAAGC





AATGACTCTTGAAACATGTAGCATCGACATTGCAAGGAGCCTCCGGAAGCTCTCCTGGGCCCCACTCT





TGGGTGGGAGAAATCTTGAAGGATTAGAGACGCCAGATCCCATTGAAATTACTGCAGGAGCATTAAT





TGTTGGATCGGGCTACTGTGAACAGTGTGCTGCAGGAGACAATCGATTCACATGGTTTTTCTTGCCAT





CTGGTATCGAGATAGGAGGGGATCCCCGTGATAATCCTCCTATCCGTGTACCGTACATTGGCTCCAGG





ACTGATGAGAGGAGGGTAGCCTCAATGGCATACATCAGGGGTGCCTCGAGTAGCCTAAAAGCAGTTC





TTAGACTGGCGGGAGTGTACATCTGGGCATTCGGAGATACTCTGGAGAATTGGATAGATGCACTGGA





TTTGTCTCACACTAGAGTTAACATCACACTTGAACAGCTGCAATCCCTCACCCCACTTCCAACCTCTG





CCAATCTAACCCATCGGTTGGATGATGGCACAACTACCCTAAAGTTTACTCCTGCGAGCTCTTACACC





TTTTCAAGTTTCACTCATATATCAAATGATGAGCAATACCTGACAATTAATGACAAAACTGCAGATTC





AAATATAATCTACCAACAGTTAATGATCACTGGACTCGGAATTTTAGAAACATGGAATAATCCCCCA





ATCAATAGAACATTCGAAGAATCTACCCTACATTTGCACACTGGTGCATCATGTTGTGTCCGACCTGT





GGACTCCTGCATCATCTCAGAAGCATTAACAGTCAAGCCACATATTACAGTACCGTACAGCAATAAA





TTTGTATTTGATGAAGACCCGCTATCTGAATATGAGACTGCAAAACTGGAATCGTTATCATTTCAAGC





CCAATTAGGCAACATTGATGCTGTAGATATGACAGGTAAATTAACATTATTGTCCCAATTCACTGCAA





GGCAGATTATTAATGCAATCACTGGACTCGATGAGTCTGTCTCTCTTACTAATGATGCCATTGTTGCA





TCAGACTATGTCTCCAATTGGATTAGTGAATGCATGTATACCAAATTAGATGAATTATTTATGTATTG





TGGGTGGGAACTACTATTGGAACTATCCTATCAAATGTATTATCTGAGGGTAGTTGGGTGGAGTAATA





TAGTGGATTATTCTTACATGATCTTGAGAAGAATCCCGGGTGCAGCATTAAACAATCTGGCATCTACA





TTAAGTCATCCAAAACTTTTCCGACGAGCTATCAACCTAGATATAGTTGCCCCCTTAAATGCTCCTCA





TTTTGCATCTCTGGACTACATCAAGATGAGTGTGGATGCAATACTCTGGGGCTGTAAAAGAGTCATCA





ATGTGCTCTCCAATGGAGGGGACTTAGAATTAGTTGTGACATCTGAAGATAGCCTTATTCTCAGTGAC





CGATCCATGAATCTCATTGCAAGGAAATTAACTTTATTATCACTGATTCACCATAATGGTTTGGAACT





ACCAAAGATTAAGGGGTTCTCTCCTGATGAGAAGTGTTTCGCTTTGACAGAATTTTTGAGGAAAGTGG





TGAACTCAGGGTTGAGTTCAATAGAGAACCTATCAAATTTTATGTACAATGTGGAGAACCCACGGCTT





GCAGCATTCGCCAGCAACAATTACTACCTGACCAGAAAATTATTGAATTCAATACGAGATACTGAGT





CGGGTCAAGTAGCAGTCACCTCATATTATGAATCATTAGAATATATTGATAGTCTTAAGCTAACCCCA





CATGTGCCTGGTACCTCATGCATTGAGGATGATAGTCTATGTACAAATGATTACATAATCTGGATCAT





AGAGTCTAATGCAAACTTGGAGAAGTATCCAATTCCAAATAGCCCTGAGGATGATTCCAATTTCCATA





ACTTTAAGTTGAATGCTCCATCGCACCATACCTTACGCCCATTAGGGTTGTCATCAACTGCTTGGTAT





AAGGGTATAAGCTGTTGCAGGTACCTTGAGCGATTAAAGCTACCACAAGGTGATCATTTATATATTGC





AGAAGGTAGTGGTGCCAGTATGACAATCATAGAATACCTATTCCCAGGAAGAAAGATATATTACAAT





TCTTTATTTAGTAGTGGTGACAATCCCCCACAAAGAAATTATGCACCAATGCCTACTCAGTTCATTGA





GAGTGTCCCATACAAGCTCTGGCAAGCACACACAGATCAATATCCCGAGATTTTTGAGGACTTCATCC





CTCTATGGAACGGAAATGCCGCCATGACTGACATAGGAATGACAGCTTGTGTAGAATTCATCATCAA





TCGAGTCGGCCCAAGGACTTGCAGTTTAGTACATGTAGATTTGGAATCAAGTGCAAGCTTAAATCAA





CAATGCCTGTCAAAGCCGATAATTAATGCTATCATCACTGCTACAACTGTTTTGTGCCCTCATGGGGT





GCTTATTCTGAAATATAGTTGGTTGCCATTTACTAGATTTAGTACTTTGATCACTTTCTTATGGTGCTA





CTTTGAGAGAATCACTGTTCTTAGGAGCACATATTCTGGTCCAGCTAATCATGAGGTTTATTTAATTTG





TATCCTTGCCAACAACTTTGCATTCCAGACTGTCTCGCAGGCAACAGGAATGGCGATGACTTTAACCG





ATCAAGGGTTTACTTTGATATCACCTGAAAGAATAAATCAGTATTGGGATGGTCACTTGAAGCAAGA





ACGTATCGTAGCAGAAGCAATTGATAAGGTGGTTCTAGGAGAAGATGCTCTATTCAATTCGAGTGAT





AATGAATTAATTCTCAAATGTGGAGGGACACCAAATGCACGGAATCTTATCGATATCGAGCCAGTCG





CAACTTTCATAGAATTTGAACAACTGATCTGCACAATGTTGACAACCCACTTGAAGGAAATAATTGAT





ATAACAAGGTCTGGAACCCAGGATTATGAAAGTTTATTACTCACTCCTTACAATTTAGGTCTTCTTGG





TAAAATCAGTACGATAGTGAGATTATTAACAGAAAGGATTCTAAATCATACTATCAGGAATTGGTTG





ATCCTCCCACCTTCGCTCCGGATGATCGTGAAGCAGGACTTGGAATTCGGCATATTCAGGATTACTTC





CATCCTCAATTCTGATCGGTTCCTGAAGCTTTCTCCAAATAGGAAATACTTGATTACACAATTAACTG





CAGGCTACATTAGGAAATTGATTGAGGGGGATTGTAATATCGATCTAACCAGACCTATCCAAAAACA





AATCTGGAAAGCATTAGGTTGTGTAGTCTATTGTCACGATCCAGTAGATCAAAGGGAATCAACAGAG





TTTATTGATATAAATATTAATGAAGAAATAGACCGCGGGATCGATGGCGAGGAAATCTAAATATATC





AAGAATCAGAATTAGTTTAAGAAAAAAGAAGAGGATTAATCTTGGTTTTCCCCTTGGT.






7. CVL53


The nucleic acid sequence for CVL53 is:










(SEQ ID NO: 67)



ACCAGGGGGAAAACGAAGTGGTGACTCAAATCATCGAAGACCCTCGAGATTACATAGGTCCGGAACC






TATGGCCTTCGTGACCGACCTCGAGTCAGAGTAGTTCAATAAGGACCTATCAAGTTTGGGCAATTTTTC





GTCCCCGACACAAAAATGTCATCCGTGCTTAAAGCATATGAGCGATTCACACTCACTCAAGAACTGCA





AGATCAGAGTGAGGAAGGTACAATCCCACCTACAACACTAAAACCGGTAATCAGGGTATTTATACTAA





CCTCTAATAACCCAGAGCTAAGATCCCGGCTTCTTCTATTCTGCCTACGGATTGTTCTCAGTAATGGTG





CAAGGGATTCCCATCGCTTTGGAGCATTACTTACAATGTTTTCGCTACCATCAGCCACAATGCTCAATC





ATGTCAAATTAGCTGACCAGTCACCAGAAGCTGATATCGAAAGGGTAGAGATCGATGGCTTTGAGGA





GGGATCATTCCGCTTAATCCCCAATGCTCGTTCAGGTATGAGCCGTGGAGAGATCAATGCCTATGCTG





CACTTGCAGAAGATCTACCTGACACACTAAACCATGCAACACCTTTTGTTGATTCCGAAGTCGAGGGA





ACTGCATGGGATGAGATTGAGACTTTCTTAGATATGTGTTACAGTGTCCTAATGCAGGCATGGATAGT





GACTTGCAAGTGCATGACTGCGCCAGACCAACCTGCTGCTTCTATTGAGAAACGCCTGCAAAAATATC





GTCAGCAAGGCAGGATCAACCCGAGATATCTCCTGCAACCGGAGGCTCGAAGAATAATCCAGAATGT





AATCCGAAAGGGAATGGTGGTCAGACATTTCCTCACCTTTGAACTGCAGCTTGCCCGAGCACAAAGCC





TTGTATCAAATAGGTATTATGCTATGGTAGGGGATGTTGGAAAGTATATAGAGAATTGTGGAATGGGA





GGCTTCTTTTTGACACTAAAATATGCATTAGGAACCAGATGGCCCACACTTGCTTTAGCTGCATTTTCA





GGAGAGCTAACAAAGCTAAAGTCCCTCATGGCATTATACCAGACCCTTGGTGAGCAGGCCCGATATTT





GGCCCTATTGGAGTCACCACATTTGATGGATTTTGCTGCAGCAAACTACCCACTGCTATATAGCTATGC





TATGGGAATAGGCTATGTGTTAGATGTCAACATGAGGAACTACGCTTTCTCCAGATCATACATGAATA





AGACATATTTCCAATTGGGAATGGAAACTGCAAGAAAACAACAGGGTGCAGTTGACATGAGGATGGC





AGAAGATCTCGGTCTAACTCAAGCCGAACGCACCGAGATGGCAAATACACTTGCCAAATTGACCACA





GCAAATCGAGGGGCAGACACCAGGGGAGGAGTCAACCCGTTCTCATCTATCACTGGGACAACTCAGG





TGCCCGCTGCAGCAACAGGTGACACATTCGAGAGTTACATGGCAGCGGATCGACTGAGGCAGAGATA





TGCTGATGCAGGCACCCACGATGATGAGATGCCACCATTGGAAGAGGAGGAAGAGGACGACACATCT





GCAGGTCCACGCACTGGACTAACTCTTGAACAAGTGGCCTTGGACATCCAGAACGCAGCAGTTGGAGC





TCCCATCCATACAGATGACCTGAATGCCGCACTGGGTGATCTTGACATCTAGACAATTCAGATCCCAA





TCTTAAATCGACACACCTAATTGACCAGTTAGATGGAACTACAGTGGATTCCATAAGGTTCCTGCCTAC





CATCGGCTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCCGATGCCAATAACA





CAATCCACAATCTACAATGGATCCCACTGATCTGAGCTTCTCCCCAGATGAGATCAATAAGCTCATAG





AGACAGGCCTGAATACTGTGGAGTATTTTACTTCCCAACAAGTCACAGGAACATCCTCTCTTGGAAAG





AATACAATACCACCAGGGGTCACAGGACTACTAACCAATGCTGCAGAGGCAAAGATCCAAGAGTCAA





CCAACCATCAGAAGGGTTCAGTTGGTGGGGGCGCAAAACCAAAGAAACCGCGACCAAAAATTGCCAT





TGTGCCAGCAGATGACAAAACGGTGCCCGGAAAGCCGATCCCAAACCCTCTATTAGGTCTGGACTCCA





CCCCGAGCACCCAAACTGTGCTTGATCTAAGTGGGAAAACATTACCATCAGGATCCTATAAGGGGGTT





AAACTTGCGAAATTTGGAAAAGAAAATCTGATGACACGGTTCATCGAGGAACCCAGAGAGAATCCTA





TCGCAACCAATTCCCCCATCGATTTTAAGAGGGGCAGGGATACCGGCGGGTTCCATAGAAGGGAGTAC





TCAATCGGATGGGTGGGAGATGAAGTCAAGGTCACTGAGTGGTGCAATCCATCCTGTTCTCCAATCAC





CGCTGCAGCAAGGCGATTTGAATGCACTTGTCACCAGTGTCCAGTCACTTGCTCTGAATGTGAACGAG





ATACTTAATACAGTGAGAAATTTGGACTCTCGGATGAATCAACTGGAGACAAAAGTAGATCGCATTCT





CTCATCTCAGTCTCTAATCCAGACCATCAAGAATGACATAGTTGGACTTAAAGCAGGGATGGCTACTT





TAGAAGGAATGATTACAACTGTGAAAATCATGGACCCGGGAGTTCCCAGTAATGTTACTGTGGAAGAT





GTACGCAAGAAACTAAGTAACCATGCTGTTGTTGTGCCAGAATCATTCAATGATAGTTTCTTGACTCAA





TCTGAAGATGTAATTTCACTTGATGAGTTGGCTCGACCAACTGCAACAAGTGTTAAGAAGATTGTCAG





GAAGGTTCCTCCTCAGAAGGATCTGACTGGATTGAAGATCACACTAGAGCAATTGGCAAAGGATTGCA





TCAGCAAACCGAAGATGAGGGAAGAGTATCTCCTCAAAATCAACCAGGCTTCCAGTGAGGCTCAGCT





AATTGACCTCAAGAAAGCAATCATCCGCAGTGCAATTTGATCAAGAAACACCCAATTACACTACACTG





GTATGACACTGTACTAACCCTGAGGGTTTTAGAAAAAACGATTAACGATAAATAAGCCCGAACACTAC





ACACCACCCGAGGCAGCCATGCCATCCATCAGCATCCCCGCAGACCCCACCAATCCACGTCAATCAAT





AAAAGCGTTCCCAATTGTGATCAACCGTGATGGGGGTGAGAAAGGTCGCTTGGTTAAACAACTACGCA





CAACCTACTTGAATGACCTAGATACTCATGAGCCACTGGTGACATTCGTAAATACTTATGGATTCATCT





ACGAACAGGATCGGGGAAATACCATTGTCGGAGAGGATCAACATGGGAAGAAAAGAGAGGCTGTGA





CTGCTGCAATGGTTACCCTTGGATGTGGGCCTAATCTACCATCATTAGGGAATGTCCTGGGACAACTG





AGTGAATTCCAGGTCATTGTTAGGAAGACATCCAGCAAAGCGGAAGAGATGGTCTTTGAAATTGTTAA





GTATCCGAGAATATTTCGGGGTCATACATTAATCCAGAAAGGACTAGTCTGTGTCTCCGCAGAAAAAT





TTGTTAAGTCACCAGGGAAAGTACAATCTGGAATGGACTATCTCTTCATTCCGACATTTCTGTCAGTGA





CTTACTGTCCAGCTGCAATCAAATTTCAGGTACCTGGCCCCATGTTGAAAATGAGATCAAGATACACT





CAGAGCTTACAACTTGAACTAATGATAAGAATCCTGTGTAAGCCCGATTCGCCACTTATGAAGGTCCA





TATCCCTGACAAGGAAGGAAGAGGATGTCTTGTATCAGTATGGTTGCATGTATGCAATATCTTCAAAT





CAGGAAACAAGAATGGCAGTGAGTGGCAGGAATACTGGATGAGAAAGTGTGCTAACATGCAACTTGA





AGTGTCGATTGCAGATATGTGGGGACCAACTATCATAATTCATGCCAGAGGTCACATTCCCAAAAGTG





CTAAGTTGTTTTTTGGAAAGGGTGGATGGAGCTGCCATCCACTTCACGAAGTTGTTCCAAGTGTCACTA





AAACACTATGGTCCGTGGGCTGTGAGATTACAAAGGCGAAGGCAATAATACAAGAGAGTAGCATCTC





TCTTCTCGTGGAGACTACTGACATCATAAGTCCAAAAGTCAAAATTTCATCTAAGCATCGCCGCTTTGG





GAAATCAAATTGGGGTCTGTTCAAGAAAACCAAATCACTGCCCAACCTGACGGAGCTGGAATGACTG





ACCCCCAATCGAGACTACACCACCTCAAACTATAGGTGGGTGGTACCTCAGTGATTAATCTCGTAAGC





ACTGATCGTAGGCTACAACACACTAATATTATCCAGATTAGAGAGCTTAATTAGCTCTGTATTAATAAT





AACACTACTATTCCAATAACTGGAATCACCAGCTTGATTTATCTCCAAAATGATTCAAAGAAAACAAA





TCATATTAAGACTATCCTAAGCACGAACCCATATCGTCCTTCAAATCATGGGTACTATAATTCAATTTC





TGGTGGTCTCCTGTCTATTGGCAGGAGCAGGCAGTCTTGATCCAGCAGCCCTCATGCAAATCGGTGTC





ATTCCAACAAATGTCCGGCAACTTATGTATTATACTGAGGCCTCATCAGCATTCATTGTTGTGAAGTTA





ATGCCTACAATTGACTCGCCGATTAGTGGATGTAATATAACATCAATTTCAAGCTATAATGCAACAGT





GACAAAACTCCTACAGCCGATCGGTGAGAATTTGGAGACGATTAGGAACCAGTTGATTCCAACTCGGA





GGAGACGCCGGTTTGCAGGGGTGGTGATTGGATTAGCTGCATTAGGAGTAGCTACTGCCGCACAGGTC





ACTGCCGCAGTAGCACTAGTAAAGGCAAATGAAAATGCTGCGGCTATACTCAATCTCAAAAATGCAAT





CCAAAAAACAAATGCAGCAGTTGCAGATGTGGTCCAGGCCACACAATCACTAGGAACaGCAGTTCAAG





CAGTTCAAGATCACATAAACAGTGTGGTAAGTCCAGCAATTACAGCAGCCAATTGTAAAGCCCAAGAT





GCTATCATTGGCTCAATCCTCAATCTCTATTTGACCGAGTTGACAACTATCTTCCACAATCAAATTACA





AACCCTGCATTGAGTCCTATTACAATTCAAGCTTTAAGGATCCTACTAGGGAGTACCTTGCCGACTGTG





GTCGAAAAATCTTTCAATACCCAGATAAGTGCGGCTGAGCTTCTCTCATCAGGGTTATTGACAGGCCA





GATTGTGGGATTAGATTTGACCTATATGCAGATGGTCATAAAAATTGAGCTGCCAACTTTAACTGTAC





AACCTGCAACCCAGATCATAGATCTGGCCACCATTTCTGCATTCATTAACAATCAAGAAGTCATGGCC





CAATTACCAACACGTGTTATTGTGACTGGCAGCTTGATCCAAGCCTATCCCGCATCGCAATGCACTATT





ACACCCAACACTGTGTACTGTAGGTATAATGATGCCCAAGTACTCTCAGATGATACGATGGCTTGCCT





CCAAGGTAACTTGACAAGATGCACCTTCTCTCCAGTGGTTGGGAGCTTTCTCACTCGATTCGTGCTGTT





CGATGGAATAGTTTATGCAAATTGCAGGTCGATGTTGTGCAAGTGCATGCAGCCTGCTGCTGTGATCCT





ACAGCCGAGTTCATCCCCTGTAACTGTCATTGACATGTACAAATGTGTGAGTCTGCAGCTTGACAATCT





CAGATTCACCATCACTCAATTGGCCAATGTAACCTACAATAGCACCATCAAGCTTGAAACATCCCAGA





TCTTGCCTATTGATCCGTTGGATATATCCCAGAATCTAGCTGCGGTGAATAAGAGTCTAAGTGATGCAC





TACAACACTTAGCACAAAGTGACACATACCTTTCTGCAATCACATCAGCTACGACTACAAGTGTATTA





TCCATAATAGCAATCTGTCTTGGATCGTTAGGTTTAATATTAATAATCTTGCTCAGTGTAGTTGTGTGG





AAGTTATTGACCATTGTCGCTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAATTCAGCATTC





CACCACTCACGATCTGATCTCAGTGAGAAAAATCAACCTGCAACTCTTGGAACAAGATAAGACAGTCA





TCCATTAGTAATTTTTAAGAAAAAAACGATAGGACCGAAACTAGTATTGAAAGAACCGTCTCGGTCAA





TCTAGGTAATCGAGCTGcTACCGTCTCGGAAAGCTCAAATCGCGCGCCACCatgtcagataacggacca






cagaaccagaggaacgcacccaggattactttcggaggaccaagcgatagcaccgggagcaaccagaat







ggagagcggagcggagcaagatccaagcagagacggccccagggcctgccaaacaataccgcatcctggt







tcaccgccctgacacagcacggcaaggaggacctgaagtttccaaggggacagggagtgcctatcaac







accaatagctcccctgacgatcagatcggctactataggagggcaacaaggagaatcaggggaggcgac







ggcaagatgaaggatctgagcccacgctggtacttctactatctgggaaccggacctgaggcaggcc






tgccatatggcgccaacaaggacggaatcatctgggtggcaaccgagggcgccctgaacacaccaaagg






atcacatcggcacaagaaatcccgccaacaatgcagcaatcgtgctgcagctgccacagggaaccacac







tgcccaagggcttttacgcagagggctctcggggaggcagccaggcatctagcagatcctctagccgg







agcagaaactcctctaggaattccaccccaggaagctccaggggcacatcccctgcccgcatggca







ggaaacggaggcgacgccgccctggccctgctgctgctggatcgcctgaatcagctggagtccaagatg







tctggcaagggacagcagcagcagggacagaccgtgacaaagaagtccgccgccgaggcctctaagaa







gccaaggcagaagcgcaccgccacaaaggcctacaacgtgacccaggccttcggcaggcgcggacc







agagcagacacagggcaattttggcgaccaggagctgatcaggcagggaaccgattataagcactggc







ctcagatcgcccagttcgccccatctgccagcgccttctttggcatgtctagaatcggcatggaggtga







cccccagcggcacatggctgacctacacaggcgccatcaagctggacgataaggaccctaacttcaa







ggatcaggtcatcctgctgaacaagcacatcgacgcctataagacctttccccctacagagcccaaga







aggacaagaagaagaaggccgatgagacacaggccctgcctcagaggcagaagaagcagcagaccgt







gacactgctgccagccgccgatctggacgatttctccaaacagctgcagcagagcat







gtccagtgccgactccacccaggcttgaGCTAGCCTCCTGCCATACTTCCTACTCACA






TCATATCTATTTTAAAGAAAAAATAGGCCCGAACACTAATCGTGCCGGCAGTGCCACTGCACACACAA





CACTACACATACAATACACTACAATGGTTGCAGAAGATGCCCCTGTTAGGGGCACTTGCCGAGTATTA





TTTCGAACAACAACTTTAATTTTTCTATGCACACTATTAGCATTAAGCATCTCTATCCTTTATGAGAGTT





TAATAACCCAAAAGCAAATCATGAGCCAAGCAGGCTCAACTGGATCTAATTCTAGATTAGGAAGTATC





ACTGATCTTCTTAATAATATTCTCTCTGTCGCAAATCAGATTATATATAACTCTGCAGTCGCTCTACCTC





TACAATTGGACACTCTTGAATCAACACTCCTTACAGCCATTAAGTCTCTTCAAACAAGTGACAAGCTA





GAACAGAACTGCTCGTGGGGTGCTGCACTGATTAATGATAATAGATACATTAATGGCATCAATCAGTT





CTATTTCTCAATTGCTGAGGGTCGCAAGCTGACACTTGGCCCACTTCTTAATATACCTAGTTTCATTCC





AACTGCCACGACACCAGAGGGCTGCACCAGGATCCCATCATTCTCGCTCACCAAGACACACTGGTGTT





ATACACACAATGTTATCCTGAATGGATGCCAGGATCATGTATCCTCAAATCAATTTGTTTCCATGGGAA





TCATTGAACCCACTTCTGCCGGGTTTCCATCCTTTCGAACCCTAAAGACTCTATATCTCAGCGATGGGG





TCAATCGTAAGAGCTGCTCTATCAGTACAGTTCCGGGGGGTTGTATGATGTACTGTTTCGTCTCTACTC





AACCAGAGAGGGATGACTACTTTTCTACCGCTCCTCCAGAACAACGAATTATTATAATGTACTATAAT





GATACAATCGTGGAGCGCATAATTAATCCACCCGGGGTACTAGATGTATGGGCAACATTGAACCCAGG





AACAGGAAGCGGGGTATATTATTTAGGTTGGGTACTCTTTCCAATATATGGCGGCGTGATTAAAGATA





CGAGTTTATGGAATAATCAAGCAAATAAATACTTTATCCCCCAGATGGTTGCTGCTCTCTGCTCACAAA





ACCAGGCAACTCAAGTCCAAAATGCTAAGTCATCATACTATAGCAGCTGGTTTGGCAATCGAATGATT





CAGTCTGGGATCCTGGCATGTCCTCTTCAACAGGATCTAACCAATGAGTGTTTAGTTCTGCCCTTTTCT





AATGATCAGGTGCTTATGGGTGCTGAAGGGAGATTATACATGTATGGTGACTCGGTGTATTACTACCA





AAGAAGCAATAGTTGGTGGCCTATGACCATGCTGTATAAGGTAACCATAACATTCACTAATGGTCAGC





CATCTGCTATATCAGCTCAGAATGTGCCCACACAGCAGGTCCCTAGACCTGGGACAGGAAGCTGCTCT





GCAACAAATAGATGTCCCGGTTTTTGCTTGAAAGGAGTGTATGCTGATGCCTGGTTACTGACCAACCCT





TCGTCTACCAGTACATTTGGATCAGAAGCAACCTTCACTGGTTCTTATCTCAACGCAGCAACTCAGCGT





ATCAATCCGACGATGTATATCGCGAACAACACACAGATCATAAGCTCACAGCAATTTGGATCAAGCGG





TCAAGAAGCAGCATATGGCCACACAACTTGTTTTAGGGACACAGGCTCTGTTATGGTATACTGTATCT





ATATTATTGAATTGTCCTCATCTCTCTTAGGACAATTTCAGATTGTCCCATTTATCCGTCAGGTGACACT





ATCCTAAAGGCAGAAGCCTCCAGGTCTGACCCAGCCAATCAAAGCATTATACCAGACCATGGAATGCA





TACCAAACATTATTGACACTAATGACACACAAAATTGGTTTTAAGAAAAACCAAGAGAACAATAGGC





CAGAATGGCTGGGTCTCGGGAGATATTACTCCCTGAAGTCCATCTCAATTCACCAATTGTAAAGCATA





AGCTATACTATTACATTCTACTTGGAAACCTCCCAAATGAGATCGACATTGACGATTTAGGTCCATTAC





ATAATCAAAATTGGAATCAAATAGCACATGAAGAGTCTAACTTAGCCCAACGCTTGGTAAATGTAAGA





AATTTTCTAATTACCCACATCCCTGATCTTAGAAAGGGCCATTGGCAAGAGTATGTCAATGTAATACTG





TGGCCGCGAATTCTTCCCTTGATCCCGGATTTTAAAATCAATGACCAATTGCCTCTACTCAAAAATTGG





GACAAGTTAGTTAAAGAATCATGTTCAGTAATCAATGCGGGTACTTCCCAGTGCATTCAGAATCTCAG





CTATGGACTGACAGGTCGTGGGAACCTCTTTACACGATCACGTGAACTCTCTGGTGACCGCAGGGATA





TTGATCTTAAGACGGTTGTGGCAGCATGGCATGACTCAGACTGGAAAAGAATAAGTGATTTTTGGATT





ATGATCAAATTCCAGATGAGACAATTAATTGTTAGGCAAACAGATCATAATGATCCTGATTTAATCAC





GTATATCGAAAATAGAGAAGGCATAATCATCATAACCCCTGAACTGGTAGCATTATTTAACACTGAGA





ATCATACACTAACATACATGACCTTTGAAATTGTACTGATGGTTTCAGATATGTACGAAGGTCGTCACA





ACATTTTATCACTATGCACAGTTAGCACTTACCTGAATCCTCTGAAGAAAAGAATAACATATTTATTGA





GCCTTGTAGATAACTTAGCTTTTCAGATAGGTGATGCTGTATATAACATAATTGCTTTGCTAGAATCCT





TTGTATATGCACAGTTGCAAATGTCAGATCCCATCCCAGAACTCAGAGGACAATTCCATGCATTCGTAT





GTTCTGAGATTCTTGATGCACTAAGGGGAACTAATAGTTTCACCCAGGATGAATCAAGAACTGTGACA





ACCAATTTGATATCCCCATTCCAAGATCTGACCCCAGATCTTACGGCTGAATTGCTCTGTATAATGAGG





CTTTGGGGACACCCCATGCTCACCGCCAGTCAAGCTGCGGGAAAGGTACGCGAGTCCATGTGTGCTGG





AAAAGTATTAGACTTTCCCACCATTATGAAAACACTAGCCTTTTTCCATACTATTCTGATCAATGGATA





CAGGAGGAAGCATCATGGAGTATGGCCACCCTTAAACTTACCGGGTAATGCTTCAAAGGGTCTCACGG





AACTTATGAATGACAATACTGAGATAAGCTATGAATTCACACTTAAGCATTGGAAGGAAATCTCTCTT





ATAAAATTCAAGAAATGTTTTGATGCAGACGCAGGTGAGGAACTCAGTATATTTATGAAAGATAAAGC





AATTAGTGCCCCAAAACAAGATTGGATGAGTGTGTTTAGAAGAAGCCTAATCAAACAGCGCCATCAGC





ATCATCAGGTCCCCCTACCAAATCCATTCAATCGACGGCTATTGCTAAACTTTCTCGGAGATGACAAAT





TCGACCCGAATGTGGAGCTACAGTATGTAACATCAGGTGAGTATCTACATGATGACACGTTTTGTGCA





TCATATTCACTAAAAGAGAAGGAAATTAAACCTGATGGTCGAATTTTTGCAAAGTTGACTAAGAGAAT





GAGATCATGTCAAGTTATAGCAGAATCTCTTTTAGCGAACCATGCTGGGAAGTTAATGAAAGAGAATG





GTGTTGTGATGAATCAGCTATCATTAACAAAATCACTATTAACAATGAGTCAGATTGGAATAATATCC





GAGAAAGCTAGAAAATCGACTCGAGATAACATAAATCAACCTGGTTTCCAGAATATCCAGAGAAATA





AATCACATCACTCCAAGCAAGTCAATCAGCGAGATCCAAGTGATGACTTTGAATTGGCAGCATCTTTT





TTAACTACTGATCTCAAAAAATATTGTTTACAATGGAGGTACCAGACAATTATCCCATTTGCTCAATCA





TTAAACAGAATGTATGGTTATCCTCATCTCTTTGAGTGGATTCACTTACGGCTAATGCGTAGTACACTT





TACGTGGGGGATCCCTTCAACCCACCAGCAGATACCAGTCAATTTGATCTAGATAAAGTAATTAATGG





AGATATCTTCATTGTATCACCCAGAGGTGGAATTGAAGGGCTATGTCAAAAGGCTTGGACAATGATAT





CTATCTCTGTGATAATTCTATCTGCCACAGAGTCTGGCACACGAGTAATGAGTATGGTGCAGGGAGAT





AATCAAGCAATTGCTGTCACCACACGAGTACCAAGGAGCCTGCCGACTCTTGAGAAAAAGACTATTGC





TTTTAGATCTTGTAATCTATTCTTTGAGAGGTTAAAATGTAATAATTTTGGATTAGGTCACCATTTGAA





AGAACAAGAGACTATCATTAGTTCTCACTTCTTTGTTTATAGCAAGAGAATATTCTATCAGGGGAGGA





TTCTAACGCAAGCCTTAAAAAATGCTAGTAAGCTCTGCTTGACAGCTGATGTCCTAGGAGAATGTACC





CAATCATCATGTTCTAATCTTGCAACTACTGTCATGAGGTTAACTGAGAATGGTGTTGAAAAAGATATC





TGTTTCTACTTGAATATCTATATGACCATCAAACAGCTCTCCTATGATATCATCTTCCCTCAAGTGTCAA





TTCCTGGAGATCAGATCACATTAGAATACATAAATAATCCACACCTGGTATCACGATTGGCTCTTCTGC





CATCCCAGCTAGGAGGTCTAAACTACCTGTCATGCAGTAGGCTGTTCAATCGAAACATAGGCGACCCG





GTGGTTTCCGCAGTTGCAGATCTTAAGAGATTAATTAAATCAGGATGTATGGATTACTGGATCCTTTAT





AACTTATTAGGGAGAAAACCGGGAAACGGCTCATGGGCTACTTTAGCAGCTGACCCGTACTCAATCAA





TATAGAGTATCAATACCCCCCAACTACAGCTCTTAAGAGGCACACCCAACAAGCTCTGATGGAACTCA





GTACGAATCCAATGTTACGTGGCATATTCTCTGACAATGCACAGGCAGAAGAAAATAATCTTGCTAGA





TTTCTCCTGGATAGGGAGGTGATCTTTCCGCGTGTAGCTCACATCATCATTGAGCAAACCAGTGTCGGG





AGGAGAAAACAGATTCAAGGATATTTGGATTCAACTAGATCGATAATGAGTAAATCACTAGAAATTA





AGCCCTTGTCCAATAGGAAGCTTAATGAAATACTGGATTACAACATCAATTACCTAGCTTACAATTTG





GCATTACTCAAGAATGCTATTGAACCTCCGACTTATTTGAAAGCAATGACTCTTGAAACATGTAGCATC





GACATTGCAAGGAGCCTCCGGAAGCTCTCCTGGGCCCCACTCTTGGGTGGGAGAAATCTTGAAGGATT





AGAGACGCCAGATCCCATTGAAATTACTGCAGGAGCATTAATTGTTGGATCGGGCTACTGTGAACAGT





GTGCTGCAGGAGACAATCGATTCACATGGTTTTTCTTGCCATCTGGTATCGAGATAGGAGGGGATCCC





CGTGATAATCCTCCTATCCGTGTACCGTACATTGGCTCCAGGACTGATGAGAGGAGGGTAGCCTCAAT





GGCATACATCAGGGGTGCCTCGAGTAGCCTAAAAGCAGTTCTTAGACTGGCGGGAGTGTACATCTGGG





CATTCGGAGATACTCTGGAGAATTGGATAGATGCACTGGATTTGTCTCACACTAGAGTTAACATCACA





CTTGAACAGCTGCAATCCCTCACCCCACTTCCAACCTCTGCCAATCTAACCCATCGGTTGGATGATGGC





ACAACTACCCTAAAGTTTACTCCTGCGAGCTCTTACACCTTTTCAAGTTTCACTCATATATCAAATGAT





GAGCAATACCTGACAATTAATGACAAAACTGCAGATTCAAATATAATCTACCAACAGTTAATGATCAC





TGGACTCGGAATTTTAGAAACATGGAATAATCCCCCAATCAATAGAACATTCGAAGAATCTACCCTAC





ATTTGCACACTGGTGCATCATGTTGTGTCCGACCTGTGGACTCCTGCATCATCTCAGAAGCATTAACAG





TCAAGCCACATATTACAGTACCGTACAGCAATAAATTTGTATTTGATGAAGACCCGCTATCTGAATAT





GAGACTGCAAAACTGGAATCGTTATCATTTCAAGCCCAATTAGGCAACATTGATGCTGTAGATATGAC





AGGTAAATTAACATTATTGTCCCAATTCACTGCAAGGCAGATTATTAATGCAATCACTGGACTCGATG





AGTCTGTCTCTCTTACTAATGATGCCATTGTTGCATCAGACTATGTCTCCAATTGGATTAGTGAATGCA





TGTATACCAAATTAGATGAATTATTTATGTATTGTGGGTGGGAACTACTATTGGAACTATCCTATCAAA





TGTATTATCTGAGGGTAGTTGGGTGGAGTAATATAGTGGATTATTCTTACATGATCTTGAGAAGAATCC





CGGGTGCAGCATTAAACAATCTGGCATCTACATTAAGTCATCCAAAACTTTTCCGACGAGCTATCAAC





CTAGATATAGTTGCCCCCTTAAATGCTCCTCATTTTGCATCTCTGGACTACATCAAGATGAGTGTGGAT





GCAATACTCTGGGGCTGTAAAAGAGTCATCAATGTGCTCTCCAATGGAGGGGACTTAGAATTAGTTGT





GACATCTGAAGATAGCCTTATTCTCAGTGACCGATCCATGAATCTCATTGCAAGGAAATTAACTTTATT





ATCACTGATTCACCATAATGGTTTGGAACTACCAAAGATTAAGGGGTTCTCTCCTGATGAGAAGTGTTT





CGCTTTGACAGAATTTTTGAGGAAAGTGGTGAACTCAGGGTTGAGTTCAATAGAGAACCTATCAAATT





TTATGTACAATGTGGAGAACCCACGGCTTGCAGCATTCGCCAGCAACAATTACTACCTGACCAGAAAA





TTATTGAATTCAATACGAGATACTGAGTCGGGTCAAGTAGCAGTCACCTCATATTATGAATCATTAGA





ATATATTGATAGTCTTAAGCTAACCCCACATGTGCCTGGTACCTCATGCATTGAGGATGATAGTCTATG





TACAAATGATTACATAATCTGGATCATAGAGTCTAATGCAAACTTGGAGAAGTATCCAATTCCAAATA





GCCCTGAGGATGATTCCAATTTCCATAACTTTAAGTTGAATGCTCCATCGCACCATACCTTACGCCCAT





TAGGGTTGTCATCAACTGCTTGGTATAAGGGTATAAGCTGTTGCAGGTACCTTGAGCGATTAAAGCTA





CCACAAGGTGATCATTTATATATTGCAGAAGGTAGTGGTGCCAGTATGACAATCATAGAATACCTATT





CCCAGGAAGAAAGATATATTACAATTCTTTATTTAGTAGTGGTGACAATCCCCCACAAAGAAATTATG





CACCAATGCCTACTCAGTTCATTGAGAGTGTCCCATACAAGCTCTGGCAAGCACACACAGATCAATAT





CCCGAGATTTTTGAGGACTTCATCCCTCTATGGAACGGAAATGCCGCCATGACTGACATAGGAATGAC





AGCTTGTGTAGAATTCATCATCAATCGAGTCGGCCCAAGGACTTGCAGTTTAGTACATGTAGATTTGG





AATCAAGTGCAAGCTTAAATCAACAATGCCTGTCAAAGCCGATAATTAATGCTATCATCACTGCTACA





ACTGTTTTGTGCCCTCATGGGGTGCTTATTCTGAAATATAGTTGGTTGCCATTTACTAGATTTAGTACTT





TGATCACTTTCTTATGGTGCTACTTTGAGAGAATCACTGTTCTTAGGAGCACATATTCTGGTCCAGCTA





ATCATGAGGTTTATTTAATTTGTATCCTTGCCAACAACTTTGCATTCCAGACTGTCTCGCAGGCAACAG





GAATGGCGATGACTTTAACCGATCAAGGGTTTACTTTGATATCACCTGAAAGAATAAATCAGTATTGG





GATGGTCACTTGAAGCAAGAACGTATCGTAGCAGAAGCAATTGATAAGGTGGTTCTAGGAGAAGATG





CTCTATTCAATTCGAGTGATAATGAATTAATTCTCAAATGTGGAGGGACACCAAATGCACGGAATCTT





ATCGATATCGAGCCAGTCGCAACTTTCATAGAATTTGAACAACTGATCTGCACAATGTTGACAACCCA





CTTGAAGGAAATAATTGATATAACAAGGTCTGGAACCCAGGATTATGAAAGTTTATTACTCACTCCTT





ACAATTTAGGTCTTCTTGGTAAAATCAGTACGATAGTGAGATTATTAACAGAAAGGATTCTAAATCAT





ACTATCAGGAATTGGTTGATCCTCCCACCTTCGCTCCGGATGATCGTGAAGCAGGACTTGGAATTCGG





CATATTCAGGATTACTTCCATCCTCAATTCTGATCGGTTCCTGAAGCTTTCTCCAAATAGGAAATACTT





GATTACACAATTAACTGCAGGCTACATTAGGAAATTGATTGAGGGGGATTGTAATATCGATCTAACCA





GACCTATCCAAAAACAAATCTGGAAAGCATTAGGTTGTGTAGTCTATTGTCACGATCCAGTAGATCAA





AGGGAATCAACAGAGTTTATTGATATAAATATTAATGAAGAAATAGACCGCGGGATCGATGGCGAGG





AAATCTAAATATATCAAGAATCAGAATTAGTTTAAGAAAAAAGAAGAGGATTAATCTTGGTTTTCCCC





TTGGT.






8. CVL54


The nucleic acid sequence for CVL54 is:










(SEQ ID NO: 68)



ACCAGGGGGAAAACGAAGTGGTGACTCAAATCATCGAAGACCCTCGAGATTACATAGGTCCGGAACC






TATGGCCTTCGTGACCGACCTCGAGTCAGAGTAGTTCAATAAGGACCTATCAAGTTTGGGCAATTTTTC





GTCCCCGACACAAAAATGTCATCCGTGCTTAAAGCATATGAGCGATTCACACTCACTCAAGAACTGCA





AGATCAGAGTGAGGAAGGTACAATCCCACCTACAACACTAAAACCGGTAATCAGGGTATTTATACTAA





CCTCTAATAACCCAGAGCTAAGATCCCGGCTTCTTCTATTCTGCCTACGGATTGTTCTCAGTAATGGTG





CAAGGGATTCCCATCGCTTTGGAGCATTACTTACAATGTTTTCGCTACCATCAGCCACAATGCTCAATC





ATGTCAAATTAGCTGACCAGTCACCAGAAGCTGATATCGAAAGGGTAGAGATCGATGGCTTTGAGGA





GGGATCATTCCGCTTAATCCCCAATGCTCGTTCAGGTATGAGCCGTGGAGAGATCAATGCCTATGCTG





CACTTGCAGAAGATCTACCTGACACACTAAACCATGCAACACCTTTTGTTGATTCCGAAGTCGAGGGA





ACTGCATGGGATGAGATTGAGACTTTCTTAGATATGTGTTACAGTGTCCTAATGCAGGCATGGATAGT





GACTTGCAAGTGCATGACTGCGCCAGACCAACCTGCTGCTTCTATTGAGAAACGCCTGCAAAAATATC





GTCAGCAAGGCAGGATCAACCCGAGATATCTCCTGCAACCGGAGGCTCGAAGAATAATCCAGAATGT





AATCCGAAAGGGAATGGTGGTCAGACATTTCCTCACCTTTGAACTGCAGCTTGCCCGAGCACAAAGCC





TTGTATCAAATAGGTATTATGCTATGGTAGGGGATGTTGGAAAGTATATAGAGAATTGTGGAATGGGA





GGCTTCTTTTTGACACTAAAATATGCATTAGGAACCAGATGGCCCACACTTGCTTTAGCTGCATTTTCA





GGAGAGCTAACAAAGCTAAAGTCCCTCATGGCATTATACCAGACCCTTGGTGAGCAGGCCCGATATTT





GGCCCTATTGGAGTCACCACATTTGATGGATTTTGCTGCAGCAAACTACCCACTGCTATATAGCTATGC





TATGGGAATAGGCTATGTGTTAGATGTCAACATGAGGAACTACGCTTTCTCCAGATCATACATGAATA





AGACATATTTCCAATTGGGAATGGAAACTGCAAGAAAACAACAGGGTGCAGTTGACATGAGGATGGC





AGAAGATCTCGGTCTAACTCAAGCCGAACGCACCGAGATGGCAAATACACTTGCCAAATTGACCACA





GCAAATCGAGGGGCAGACACCAGGGGAGGAGTCAACCCGTTCTCATCTATCACTGGGACAACTCAGG





TGCCCGCTGCAGCAACAGGTGACACATTCGAGAGTTACATGGCAGCGGATCGACTGAGGCAGAGATA





TGCTGATGCAGGCACCCACGATGATGAGATGCCACCATTGGAAGAGGAGGAAGAGGACGACACATCT





GCAGGTCCACGCACTGGACTAACTCTTGAACAAGTGGCCTTGGACATCCAGAACGCAGCAGTTGGAGC





TCCCATCCATACAGATGACCTGAATGCCGCACTGGGTGATCTTGACATCTAGACAATTCAGATCCCAA





TCTTAAATCGACACACCTAATTGACCAGTTAGATGGAACTACAGTGGATTCCATAAGGTTCCTGCCTAC





CATCGGCTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCCGATGCCAATAACA





CAATCCACAATCTACAATGGATCCCACTGATCTGAGCTTCTCCCCAGATGAGATCAATAAGCTCATAG





AGACAGGCCTGAATACTGTGGAGTATTTTACTTCCCAACAAGTCACAGGAACATCCTCTCTTGGAAAG





AATACAATACCACCAGGGGTCACAGGACTACTAACCAATGCTGCAGAGGCAAAGATCCAAGAGTCAA





CCAACCATCAGAAGGGTTCAGTTGGTGGGGGCGCAAAACCAAAGAAACCGCGACCAAAAATTGCCAT





TGTGCCAGCAGATGACAAAACGGTGCCCGGAAAGCCGATCCCAAACCCTCTATTAGGTCTGGACTCCA





CCCCGAGCACCCAAACTGTGCTTGATCTAAGTGGGAAAACATTACCATCAGGATCCTATAAGGGGGTT





AAACTTGCGAAATTTGGAAAAGAAAATCTGATGACACGGTTCATCGAGGAACCCAGAGAGAATCCTA





TCGCAACCAATTCCCCCATCGATTTTAAGAGGGGCAGGGATACCGGCGGGTTCCATAGAAGGGAGTAC





TCAATCGGATGGGTGGGAGATGAAGTCAAGGTCACTGAGTGGTGCAATCCATCCTGTTCTCCAATCAC





CGCTGCAGCAAGGCGATTTGAATGCACTTGTCACCAGTGTCCAGTCACTTGCTCTGAATGTGAACGAG





ATACTTAATACAGTGAGAAATTTGGACTCTCGGATGAATCAACTGGAGACAAAAGTAGATCGCATTCT





CTCATCTCAGTCTCTAATCCAGACCATCAAGAATGACATAGTTGGACTTAAAGCAGGGATGGCTACTT





TAGAAGGAATGATTACAACTGTGAAAATCATGGACCCGGGAGTTCCCAGTAATGTTACTGTGGAAGAT





GTACGCAAGAAACTAAGTAACCATGCTGTTGTTGTGCCAGAATCATTCAATGATAGTTTCTTGACTCAA





TCTGAAGATGTAATTTCACTTGATGAGTTGGCTCGACCAACTGCAACAAGTGTTAAGAAGATTGTCAG





GAAGGTTCCTCCTCAGAAGGATCTGACTGGATTGAAGATCACACTAGAGCAATTGGCAAAGGATTGCA





TCAGCAAACCGAAGATGAGGGAAGAGTATCTCCTCAAAATCAACCAGGCTTCCAGTGAGGCTCAGCT





AATTGACCTCAAGAAAGCAATCATCCGCAGTGCAATTTGATCAAGAAACACCCAATTACACTACACTG





GTATGACACTGTACTAACCCTGAGGGTTTTAGAAAAAACGATTAACGATAAATAAGCCCGAACACTAC





ACACCACCCGAGGCAGCCATGCCATCCATCAGCATCCCCGCAGACCCCACCAATCCACGTCAATCAAT





AAAAGCGTTCCCAATTGTGATCAACCGTGATGGGGGTGAGAAAGGTCGCTTGGTTAAACAACTACGCA





CAACCTACTTGAATGACCTAGATACTCATGAGCCACTGGTGACATTCGTAAATACTTATGGATTCATCT





ACGAACAGGATCGGGGAAATACCATTGTCGGAGAGGATCAACATGGGAAGAAAAGAGAGGCTGTGA





CTGCTGCAATGGTTACCCTTGGATGTGGGCCTAATCTACCATCATTAGGGAATGTCCTGGGACAACTG





AGTGAATTCCAGGTCATTGTTAGGAAGACATCCAGCAAAGCGGAAGAGATGGTCTTTGAAATTGTTAA





GTATCCGAGAATATTTCGGGGTCATACATTAATCCAGAAAGGACTAGTCTGTGTCTCCGCAGAAAAAT





TTGTTAAGTCACCAGGGAAAGTACAATCTGGAATGGACTATCTCTTCATTCCGACATTTCTGTCAGTGA





CTTACTGTCCAGCTGCAATCAAATTTCAGGTACCTGGCCCCATGTTGAAAATGAGATCAAGATACACT





CAGAGCTTACAACTTGAACTAATGATAAGAATCCTGTGTAAGCCCGATTCGCCACTTATGAAGGTCCA





TATCCCTGACAAGGAAGGAAGAGGATGTCTTGTATCAGTATGGTTGCATGTATGCAATATCTTCAAAT





CAGGAAACAAGAATGGCAGTGAGTGGCAGGAATACTGGATGAGAAAGTGTGCTAACATGCAACTTGA





AGTGTCGATTGCAGATATGTGGGGACCAACTATCATAATTCATGCCAGAGGTCACATTCCCAAAAGTG





CTAAGTTGTTTTTTGGAAAGGGTGGATGGAGCTGCCATCCACTTCACGAAGTTGTTCCAAGTGTCACTA





AAACACTATGGTCCGTGGGCTGTGAGATTACAAAGGCGAAGGCAATAATACAAGAGAGTAGCATCTC





TCTTCTCGTGGAGACTACTGACATCATAAGTCCAAAAGTCAAAATTTCATCTAAGCATCGCCGCTTTGG





GAAATCAAATTGGGGTCTGTTCAAGAAAACCAAATCACTGCCCAACCTGACGGAGCTGGAATGACTG





ACCCCCAATCGAGACTACACCACCTCAAACTATAGGTGGGTGGTACCTCAGTGATTAATCTCGTAAGC





ACTGATCGTAGGCTACAACACACTAATATTATCCAGATTAGAGAGCTTAATTAGCTCTGTATTAATAAT





AACACTACTATTCCAATAACTGGAATCACCAGCTTGATTTATCTCCAAAATGATTCAAAGAAAACAAA





TCATATTAAGACTATCCTAAGCACGAACCCATATCGTCCTTCAAATCATGGGTACTATAATTCAATTTC





TGGTGGTCTCCTGTCTATTGGCAGGAGCAGGCAGTCTTGATCCAGCAGCCCTCATGCAAATCGGTGTC





ATTCCAACAAATGTCCGGCAACTTATGTATTATACTGAGGCCTCATCAGCATTCATTGTTGTGAAGTTA





ATGCCTACAATTGACTCGCCGATTAGTGGATGTAATATAACATCAATTTCAAGCTATAATGCAACAGT





GACAAAACTCCTACAGCCGATCGGTGAGAATTTGGAGACGATTAGGAACCAGTTGATTCCAACTCGGA





GGAGACGCCGGTTTGCAGGGGTGGTGATTGGATTAGCTGCATTAGGAGTAGCTACTGCCGCACAGGTC





ACTGCCGCAGTAGCACTAGTAAAGGCAAATGAAAATGCTGCGGCTATACTCAATCTCAAAAATGCAAT





CCAAAAAACAAATGCAGCAGTTGCAGATGTGGTCCAGGCCACACAATCACTAGGAACaGCAGTTCAAG





CAGTTCAAGATCACATAAACAGTGTGGTAAGTCCAGCAATTACAGCAGCCAATTGTAAAGCCCAAGAT





GCTATCATTGGCTCAATCCTCAATCTCTATTTGACCGAGTTGACAACTATCTTCCACAATCAAATTACA





AACCCTGCATTGAGTCCTATTACAATTCAAGCTTTAAGGATCCTACTAGGGAGTACCTTGCCGACTGTG





GTCGAAAAATCTTTCAATACCCAGATAAGTGCGGCTGAGCTTCTCTCATCAGGGTTATTGACAGGCCA





GATTGTGGGATTAGATTTGACCTATATGCAGATGGTCATAAAAATTGAGCTGCCAACTTTAACTGTAC





AACCTGCAACCCAGATCATAGATCTGGCCACCATTTCTGCATTCATTAACAATCAAGAAGTCATGGCC





CAATTACCAACACGTGTTATTGTGACTGGCAGCTTGATCCAAGCCTATCCCGCATCGCAATGCACTATT





ACACCCAACACTGTGTACTGTAGGTATAATGATGCCCAAGTACTCTCAGATGATACGATGGCTTGCCT





CCAAGGTAACTTGACAAGATGCACCTTCTCTCCAGTGGTTGGGAGCTTTCTCACTCGATTCGTGCTGTT





CGATGGAATAGTTTATGCAAATTGCAGGTCGATGTTGTGCAAGTGCATGCAGCCTGCTGCTGTGATCCT





ACAGCCGAGTTCATCCCCTGTAACTGTCATTGACATGTACAAATGTGTGAGTCTGCAGCTTGACAATCT





CAGATTCACCATCACTCAATTGGCCAATGTAACCTACAATAGCACCATCAAGCTTGAAACATCCCAGA





TCTTGCCTATTGATCCGTTGGATATATCCCAGAATCTAGCTGCGGTGAATAAGAGTCTAAGTGATGCAC





TACAACACTTAGCACAAAGTGACACATACCTTTCTGCAATCACATCAGCTACGACTACAAGTGTATTA





TCCATAATAGCAATCTGTCTTGGATCGTTAGGTTTAATATTAATAATCTTGCTCAGTGTAGTTGTGTGG





AAGTTATTGACCATTGTCGCTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAATTCAGCATTC





CACCACTCACGATCTGATCTCAGTGAGAAAAATCAACCTGCAACTCTTGGAACAAGATAAGACAGTCA





TCCATTAGTAATTTTTAAGAAAAAAACGATAGGACCGAAACTAGTATTGAAAGAACCGTCTCGGTCAA





TCTAGGTAATCGAGCTGcTACCGTCTCGGAAAGCTCAAATCGCGCGCCACCatgtcagataacggacca






cagaaccagaggaacgcacccaggattactttcggaggaccaagcgatagcaccgggagcaaccagaatg







gagagcggagcggagcaagatccaagcagagacggccccagggcctgccaaacaataccgcatcctggttc







accgccctgacacagcacggcaaggaggacctgaagtttccaaggggacagggagtgcctatcaacaccaa







tagctcccctgacgatcagatcggctactataggagggcaacaaggagaatcaggggaggcgacggcaa







gatgaaggatctgagcccacgctggtacttctactatctgggaaccggacctgaggcaggcctgc







catatggcgccaacaaggacggaatcatctgggtggcaaccgagggcgccctgaacacaccaaagga







tcacatcggcacaagaaatcccgccaacaatgcagcaatcgtgctgcagctgccacagggaaccacactg







cccaagggcttttacgcagagggctctcggggaggcagccaggcatctagcagatcctctagccggagc







agaaactcctctaggaattccaccccaggaagctccaggggcacatcccctgcccgcatggcaggaaa







cggaggcgacgccgccctggccctgctgctgctggatcgcctgaatcagctggagtccaagatgtc







tggcaagggacagcagcagcagggacagaccgtgacaaagaagtccgccgccgaggcctctaagaa







gccaaggcagaagcgcaccgccacaaaggcctacaacgtgacccaggccttcggcaggcgcggacca







gagcagacacagggcaattttggcgaccaggagctgatcaggcagggaaccgattataagcact







ggcctcagatcgcccagttcgccccatctgccagcgccttctttggcatgtctagaatcggcatgg







aggtgacccccagcggcacatggctgacctacacaggcgccatcaagctggacgataaggaccct







aacttcaaggatcaggtcatcctgctgaacaagcacatcgacgcctataagacctttccccctacaga







gcccaagaaggacaagaagaagaaggccgatgagacacaggccctgcctcagaggcagaagaagcag







cagaccgtgacactgctgccagccgccgatctggacgatttctccaaacagctgcagcagagcatgtc







cagtgccgactccacccaggcttgaGCTAGCCTCCTGCCATACTTCCTACTCACA






TCATATCTATTTTAAAGAAAAAATAGGCCCGAACACTAATCGTGCCGGCAGTGCCACTGCACACACAA





CACTACACATACAATACACTACAATGGTTGCAGAAGATGCCCCTGTTAGGGGCACTTGCCGAGTATTA





TTTCGAACAACAACTTTAATTTTTCTATGCACACTATTAGCATTAAGCATCTCTATCCTTTATGAGAGTT





TAATAACCCAAAAGCAAATCATGAGCCAAGCAGGCTCAACTGGATCTAATTCTAGATTAGGAAGTATC





ACTGATCTTCTTAATAATATTCTCTCTGTCGCAAATCAGATTATATATAACTCTGCAGTCGCTCTACCTC





TACAATTGGACACTCTTGAATCAACACTCCTTACAGCCATTAAGTCTCTTCAAACAAGTGACAAGCTA





GAACAGAACTGCTCGTGGGGTGCTGCACTGATTAATGATAATAGATACATTAATGGCATCAATCAGTT





CTATTTCTCAATTGCTGAGGGTCGCAAGCTGACACTTGGCCCACTTCTTAATATACCTAGTTTCATTCC





AACTGCCACGACACCAGAGGGCTGCACCAGGATCCCATCATTCTCGCTCACCAAGACACACTGGTGTT





ATACACACAATGTTATCCTGAATGGATGCCAGGATCATGTATCCTCAAATCAATTTGTTTCCATGGGAA





TCATTGAACCCACTTCTGCCGGGTTTCCATCCTTTCGAACCCTAAAGACTCTATATCTCAGCGATGGGG





TCAATCGTAAGAGCTGCTCTATCAGTACAGTTCCGGGGGGTTGTATGATGTACTGTTTCGTCTCTACTC





AACCAGAGAGGGATGACTACTTTTCTACCGCTCCTCCAGAACAACGAATTATTATAATGTACTATAAT





GATACAATCGTGGAGCGCATAATTAATCCACCCGGGGTACTAGATGTATGGGCAACATTGAACCCAGG





AACAGGAAGCGGGGTATATTATTTAGGTTGGGTACTCTTTCCAATATATGGCGGCGTGATTAAAGATA





CGAGTTTATGGAATAATCAAGCAAATAAATACTTTATCCCCCAGATGGTTGCTGCTCTCTGCTCACAAA





ACCAGGCAACTCAAGTCCAAAATGCTAAGTCATCATACTATAGCAGCTGGTTTGGCAATCGAATGATT





CAGTCTGGGATCCTGGCATGTCCTCTTCAACAGGATCTAACCAATGAGTGTTTAGTTCTGCCCTTTTCT





AATGATCAGGTGCTTATGGGTGCTGAAGGGAGATTATACATGTATGGTGACTCGGTGTATTACTACCA





AAGAAGCAATAGTTGGTGGCCTATGACCATGCTGTATAAGGTAACCATAACATTCACTAATGGTCAGC





CATCTGCTATATCAGCTCAGAATGTGCCCACACAGCAGGTCCCTAGACCTGGGACAGGAAGCTGCTCT





GCAACAAATAGATGTCCCGGTTTTTGCTTGAAAGGAGTGTATGCTGATGCCTGGTTACTGACCAACCCT





TCGTCTACCAGTACATTTGGATCAGAAGCAACCTTCACTGGTTCTTATCTCAACGCAGCAACTCAGCGT





ATCAATCCGACGATGTATATCGCGAACAACACACAGATCATAAGCTCACAGCAATTTGGATCAAGCGG





TCAAGAAGCAGCATATGGCCACACAACTTGTTTTAGGGACACAGGCTCTGTTATGGTATACTGTATCT





ATATTATTGAATTGTCCTCATCTCTCTTAGGACAATTTCAGATTGTCCCATTTATCCGTCAGGTGACACT





ATCCTAAACCTGCTATAGGCTATCCACTGCATCATCTCTTTTTAAGAAAAAAATAGGCCCGGACGGGTT





AGCAACAAGCGACTGCCGGTGCCAACAACACAATCCACAATCTACAGTCGACGCGGCCGCCACCatgttc





gtgttcctggtgctgctgccactggtcagcagccagtgcgtgaatttcactacccggacccagctgc





ctcctgcttatacaaacagcttcaccaggggagtgtactaccccgataaggtgttccgcagctctgtgct





gcacagcacccaggacttgtttcttcccttcttcagcaacgtgacctggttccacgccatccacgtgt





ccggcaccaacggcaccaaaagattcgccaatcctgtgctgcctttcaacgatggcgtgtactttgcctc





tacagagaagtctaacatcatcagaggctggatcttcggcacaaccctggattctaaaacccagagcctg





ctgatcgtgaacaatgccaccaatgtagtgatcaaggtttgtgagttccagttctgcaacgaccccttt





ctgggcgtttactaccacaagaacaacaaaagctggatggaaagcgagttcagggtgtactctagcgcc





aacaactgtaccttcgagtacgtgagccagccttttctgatggacctggagggcaagcagggcaacttc





aaaaacctgcgggagttcgtgtttaagaacatcgacggatacttcaagatttactccaagcacaccc





caattaacttggttagaggactgccccaaggcttcagcgccctggaacccctggtggacctgccta





tcggcatcaacatcacaagattccaaaccctgcatagaagctatctgacaccaggcgactctagctc





tggatggacagccggcgccgctgcttattacgtgggctacctgcagcctagaaccttcctcctgaaata





caacgagaacggaaccatcaccgacgccgtggactgcgccctggatcctctgagcgagacaaagtg





caccctgaagtccttcaccgtcgaaaagggcatctaccaaacaagcaacttcagagtgcagcctac





tgagagcatcgtgcggtttccaaacatcaccaacctgtgtccttttggcgaggtgttcaacgccacc





cggttcgcttccgtgtacgcctggaatagaaagcggatcagcaactgcgtggccgactacagcgtgct





gtataatagcgcctcattttctacttttaaatgttacggcgtgtctcctacaaagctgaacgatctgt





gcttcacaaatgtgtacgccgatagcttcgtgattagaggcgacgaggtgcggcagatcgcccctg





gccagaccggcaacatcgctgactacaactacaagctgcctgacgacttcaccggctgtgtgatc





gcatggaacagcaataacctggactctaaggtgggcggaaactacaattacctgtacagactgt





tcagaaagagcaacctgaagcccttcgagagagatatctccacagaaatctatcaggccggatctacac





cttgtaatggcgtgaagggcttcaactgctacttccctctgcaatcctacggctttcagcccacatacgg





cgtgggctaccagccataccgggtcgtggtgctgagcttcgagctgctgcacgcccctgccacagtgtg





cggccctaagaagagcaccaatctggtaaagaacaagtgcgtcaacttcaatttcaacggcctgacc





gggaccggagtgctgaccgaaagcaacaagaaattcctgccgttccagcagttcggcagagatatcgccgac





accaccgatgccgtgcgggacccccagacacttgaaatcctggacatcaccccttgcagttttggcggc





gtgtccgtgatcacacctggaacaaacaccagcaaccaggtggccgtgctgtaccagggcgtca





actgcaccgaggtccccgtggccatccacgccgatcagctgacacctacatggcgggtg





tactctaccggcagcaacgtgttccaaaccagagccggctgcctgatcggcgctga





gcacgtgaacaacagctacgagtgcgacattcctatcggtgctggcatctgcgcctcttaccag





acacagacaaacagccccagaagagcgagaagcgtggctagtcagagcatcatcgcctacaccatg





agcctgggcgtggagaacagcgtggcctactctaacaatagcatcgccatcccaaccaacttcacaa





tctctgtgaccacagagatcctgcccgtgtccatgaccaagacatctgtggactgcacaatgtatatct





gtggcgattctaccgagtgcagcaacctgctgctccagtacggcagcttttgtacccagctgaataga





gccctgacaggcatcgccgtggagcaggataagaacacacaggaggtgttcgcccaggtgaagcaaat





ctacaagaccccccctatcaaggactttggcggcttcaatttttcccagatcctgcctgatccatccaagc





cttctaagcggagctttatcgaggacctgctgttcaacaaggtgaccctggccgatgccggcttcatca





agcagtatggcgattgcctgggcgacatcgcagccagggacctgatctgcgcccagaagtttaatggcctg





accgtgctgccacccctgctgacagatgagatgatcgcacagtacacaagcgccctgctggccggca





ccatcacatccggatggaccttcggcgcaggagccgccctccagatcccctttgccatgcagatggcctat





aggttcaacggcatcggcgtgacccagaatgtgctgtacgagaaccagaagctgatcgccaatcagtttaa





ctccgccatcggcaagatccaggacagcctgtcctctacagccagcgccctgggcaagctccaggatg





tggtgaatcagaacgcccaggccctgaataccctggtgaagcagctgagcagcaacttcggcgccatct





ctagcgtgctgaatgacatcctgagccggctggacaaggtggaggcagaggtgcagatcgaccggctgatca





ccggccggctccagagcctccagacctatgtgacacagcagctgatcagggccgccgagatcagggccag





cgccaatctggcagcaaccaagatgtccgagtgcgtgctgggccagtctaagagagtggacttttgtggc





aagggctatcacctgatgtccttccctcagtctgccccacacggcgtggtgtttctgcacgtgacctac





gtgcccgcccaggagaagaacttcaccacagcccctgccatctgccacgatggcaaggcccactttcca





agggagggcgtgttcgtgtccaacggcacccactggtttgtgacacagcgcaatttctacgagcccc





agatcatcaccacagacaacaccttcgtgagcggcaactgtgacgtggtcatcggcatcgtgaacaat





accgtgtatgatccactccagcccgagctggacagctttaaggaggagctggataagtatttcaagaa





tcacacctcccctgacgtggatctgggcgacatcagcggcatcaatgcctccgtggtgaacatccag





aaggagatcgaccgcctgaacgaggtggctaagaatctgaacgagagcctgatcgacctccaggagc





tgggcaagtatgagcagtacatcaagtggccctggtacatctggctgggcttcatcgccggcctgatcg





ccatcgtgatggtgaccatcatgctgtgctgtatgacatcctgctgttcttgcctgaagggctgctgtagct





gtggctcctgctgtAAGTTATTGACCATTGTCGTTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAAA





TGACGTACGAGGCAGAAGCCTCCAGGTCTGACCCAGCCAATCAAAGCATTATACCAGACCATGGAAT





GCATACCAAACATTATTGACACTAATGACACACAAAATTGGTTTTAAGAAAAACCAAGAGAACAATA





GGCCAGAATGGCTGGGTCTCGGGAGATATTACTCCCTGAAGTCCATCTCAATTCACCAATTGTAAAGC





ATAAGCTATACTATTACATTCTACTTGGAAACCTCCCAAATGAGATCGACATTGACGATTTAGGTCCAT





TACATAATCAAAATTGGAATCAAATAGCACATGAAGAGTCTAACTTAGCCCAACGCTTGGTAAATGTA





AGAAATTTTCTAATTACCCACATCCCTGATCTTAGAAAGGGCCATTGGCAAGAGTATGTCAATGTAAT





ACTGTGGCCGCGAATTCTTCCCTTGATCCCGGATTTTAAAATCAATGACCAATTGCCTCTACTCAAAAA





TTGGGACAAGTTAGTTAAAGAATCATGTTCAGTAATCAATGCGGGTACTTCCCAGTGCATTCAGAATC





TCAGCTATGGACTGACAGGTCGTGGGAACCTCTTTACACGATCACGTGAACTCTCTGGTGACCGCAGG





GATATTGATCTTAAGACGGTTGTGGCAGCATGGCATGACTCAGACTGGAAAAGAATAAGTGATTTTTG





GATTATGATCAAATTCCAGATGAGACAATTAATTGTTAGGCAAACAGATCATAATGATCCTGATTTAA





TCACGTATATCGAAAATAGAGAAGGCATAATCATCATAACCCCTGAACTGGTAGCATTATTTAACACT





GAGAATCATACACTAACATACATGACCTTTGAAATTGTACTGATGGTTTCAGATATGTACGAAGGTCG





TCACAACATTTTATCACTATGCACAGTTAGCACTTACCTGAATCCTCTGAAGAAAAGAATAACATATTT





ATTGAGCCTTGTAGATAACTTAGCTTTTCAGATAGGTGATGCTGTATATAACATAATTGCTTTGCTAGA





ATCCTTTGTATATGCACAGTTGCAAATGTCAGATCCCATCCCAGAACTCAGAGGACAATTCCATGCATT





CGTATGTTCTGAGATTCTTGATGCACTAAGGGGAACTAATAGTTTCACCCAGGATGAATCAAGAACTG





TGACAACCAATTTGATATCCCCATTCCAAGATCTGACCCCAGATCTTACGGCTGAATTGCTCTGTATAA





TGAGGCTTTGGGGACACCCCATGCTCACCGCCAGTCAAGCTGCGGGAAAGGTACGCGAGTCCATGTGT





GCTGGAAAAGTATTAGACTTTCCCACCATTATGAAAACACTAGCCTTTTTCCATACTATTCTGATCAAT





GGATACAGGAGGAAGCATCATGGAGTATGGCCACCCTTAAACTTACCGGGTAATGCTTCAAAGGGTCT





CACGGAACTTATGAATGACAATACTGAGATAAGCTATGAATTCACACTTAAGCATTGGAAGGAAATCT





CTCTTATAAAATTCAAGAAATGTTTTGATGCAGACGCAGGTGAGGAACTCAGTATATTTATGAAAGAT





AAAGCAATTAGTGCCCCAAAACAAGATTGGATGAGTGTGTTTAGAAGAAGCCTAATCAAACAGCGCC





ATCAGCATCATCAGGTCCCCCTACCAAATCCATTCAATCGACGGCTATTGCTAAACTTTCTCGGAGATG





ACAAATTCGACCCGAATGTGGAGCTACAGTATGTAACATCAGGTGAGTATCTACATGATGACACGTTT





TGTGCATCATATTCACTAAAAGAGAAGGAAATTAAACCTGATGGTCGAATTTTTGCAAAGTTGACTAA





GAGAATGAGATCATGTCAAGTTATAGCAGAATCTCTTTTAGCGAACCATGCTGGGAAGTTAATGAAAG





AGAATGGTGTTGTGATGAATCAGCTATCATTAACAAAATCACTATTAACAATGAGTCAGATTGGAATA





ATATCCGAGAAAGCTAGAAAATCGACTCGAGATAACATAAATCAACCTGGTTTCCAGAATATCCAGAG





AAATAAATCACATCACTCCAAGCAAGTCAATCAGCGAGATCCAAGTGATGACTTTGAATTGGCAGCAT





CTTTTTTAACTACTGATCTCAAAAAATATTGTTTACAATGGAGGTACCAGACAATTATCCCATTTGCTC





AATCATTAAACAGAATGTATGGTTATCCTCATCTCTTTGAGTGGATTCACTTACGGCTAATGCGTAGTA





CACTTTACGTGGGGGATCCCTTCAACCCACCAGCAGATACCAGTCAATTTGATCTAGATAAAGTAATT





AATGGAGATATCTTCATTGTATCACCCAGAGGTGGAATTGAAGGGCTATGTCAAAAGGCTTGGACAAT





GATATCTATCTCTGTGATAATTCTATCTGCCACAGAGTCTGGCACACGAGTAATGAGTATGGTGCAGG





GAGATAATCAAGCAATTGCTGTCACCACACGAGTACCAAGGAGCCTGCCGACTCTTGAGAAAAAGAC





TATTGCTTTTAGATCTTGTAATCTATTCTTTGAGAGGTTAAAATGTAATAATTTTGGATTAGGTCACCAT





TTGAAAGAACAAGAGACTATCATTAGTTCTCACTTCTTTGTTTATAGCAAGAGAATATTCTATCAGGGG





AGGATTCTAACGCAAGCCTTAAAAAATGCTAGTAAGCTCTGCTTGACAGCTGATGTCCTAGGAGAATG





TACCCAATCATCATGTTCTAATCTTGCAACTACTGTCATGAGGTTAACTGAGAATGGTGTTGAAAAAG





ATATCTGTTTCTACTTGAATATCTATATGACCATCAAACAGCTCTCCTATGATATCATCTTCCCTCAAGT





GTCAATTCCTGGAGATCAGATCACATTAGAATACATAAATAATTCCACACCTGGTATCACGATTGGCTC





TTCTGCCATCCCAGCTAGGAGGTCTAAACTACCTGTCATGCAGTAGGCTGTTCAATCGAAACATAGGC





GACCCGGTGGTTTCCGCAGTTGCAGATCTTAAGAGATTAATTAAATCAGGATGTATGGATTACTGGAT





CCTTTATAACTTATTAGGGAGAAAACCGGGAAACGGCTCATGGGCTACTTTAGCAGCTGACCCGTACT





CAATCAATATAGAGTATCAATACCCCCCAACTACAGCTCTTAAGAGGCACACCCAACAAGCTCTGATG





GAACTCAGTACGAATCCAATGTTACGTGGCATATTCTCTGACAATGCACAGGCAGAAGAAAATAATCT





TGCTAGATTTCTCCTGGATAGGGAGGTGATCTTTCCGCGTGTAGCTCACATCATCATTGAGCAAACCAG





TGTCGGGAGGAGAAAACAGATTCAAGGATATTTGGATTCAACTAGATCGATAATGAGTAAATCACTAG





AAATTAAGCCCTTGTCCAATAGGAAGCTTAATGAAATACTGGATTACAACATCAATTACCTAGCTTAC





AATTTGGCATTACTCAAGAATGCTATTGAACCTCCGACTTATTTGAAAGCAATGACTCTTGAAACATGT





AGCATCGACATTGCAAGGAGCCTCCGGAAGCTCTCCTGGGCCCCACTCTTGGGTGGGAGAAATCTTGA





AGGATTAGAGACGCCAGATCCCATTGAAATTACTGCAGGAGCATTAATTGTTGGATCGGGCTACTGTG





AACAGTGTGCTGCAGGAGACAATCGATTCACATGGTTTTTCTTGCCATCTGGTATCGAGATAGGAGGG





GATCCCCGTGATAATCCTCCTATCCGTGTACCGTACATTGGCTCCAGGACTGATGAGAGGAGGGTAGC





CTCAATGGCATACATCAGGGGTGCCTCGAGTAGCCTAAAAGCAGTTCTTAGACTGGCGGGAGTGTACA





TCTGGGCATTCGGAGATACTCTGGAGAATTGGATAGATGCACTGGATTTGTCTCACACTAGAGTTAAC





ATCACACTTGAACAGCTGCAATCCCTCACCCCACTTCCAACCTCTGCCAATCTAACCCATCGGTTGGAT





GATGGCACAACTACCCTAAAGTTTACTCCTGCGAGCTCTTACACCTTTTCAAGTTTCACTCATATATCA





AATGATGAGCAATACCTGACAATTAATGACAAAACTGCAGATTCAAATATAATCTACCAACAGTTAAT





GATCACTGGACTCGGAATTTTAGAAACATGGAATAATCCCCCAATCAATAGAACATTCGAAGAATCTA





CCCTACATTTGCACACTGGTGCATCATGTTGTGTCCGACCTGTGGACTCCTGCATCATCTCAGAAGCAT





TAACAGTCAAGCCACATATTACAGTACCGTACAGCAATAAATTTGTATTTGATGAAGACCCGCTATCT





GAATATGAGACTGCAAAACTGGAATCGTTATCATTTCAAGCCCAATTAGGCAACATTGATGCTGTAGA





TATGACAGGTAAATTAACATTATTGTCCCAATTCACTGCAAGGCAGATTATTAATGCAATCACTGGACT





CGATGAGTCTGTCTCTCTTACTAATGATGCCATTGTTGCATCAGACTATGTCTCCAATTGGATTAGTGA





ATGCATGTATACCAAATTAGATGAATTATTTATGTATTGTGGGTGGGAACTACTATTGGAACTATCCTA





TCAAATGTATTATCTGAGGGTAGTTGGGTGGAGTAATATAGTGGATTATTCTTACATGATCTTGAGAAG





AATCCCGGGTGCAGCATTAAACAATCTGGCATCTACATTAAGTCATCCAAAACTTTTCCGACGAGCTA





TCAACCTAGATATAGTTGCCCCCTTAAATGCTCCTCATTTTGCATCTCTGGACTACATCAAGATGAGTG





TGGATGCAATACTCTGGGGCTGTAAAAGAGTCATCAATGTGCTCTCCAATGGAGGGGACTTAGAATTA





GTTGTGACATCTGAAGATAGCCTTATTCTCAGTGACCGATCCATGAATCTCATTGCAAGGAAATTAACT





TTATTATCACTGATTCACCATAATGGTTTGGAACTACCAAAGATTAAGGGGTTCTCTCCTGATGAGAAG





TGTTTCGCTTTGACAGAATTTTTGAGGAAAGTGGTGAACTCAGGGTTGAGTTCAATAGAGAACCTATC





AAATTTTATGTACAATGTGGAGAACCCACGGCTTGCAGCATTCGCCAGCAACAATTACTACCTGACCA





GAAAATTATTGAATTCAATACGAGATACTGAGTCGGGTCAAGTAGCAGTCACCTCATATTATGAATCA





TTAGAATATATTGATAGTCTTAAGCTAACCCCACATGTGCCTGGTACCTCATGCATTGAGGATGATAGT





CTATGTACAAATGATTACATAATCTGGATCATAGAGTCTAATGCAAACTTGGAGAAGTATCCAATTCC





AAATAGCCCTGAGGATGATTCCAATTTCCATAACTTTAAGTTGAATGCTCCATCGCACCATACCTTACG





CCCATTAGGGTTGTCATCAACTGCTTGGTATAAGGGTATAAGCTGTTGCAGGTACCTTGAGCGATTAA





AGCTACCACAAGGTGATCATTTATATATTGCAGAAGGTAGTGGTGCCAGTATGACAATCATAGAATAC





CTATTCCCAGGAAGAAAGATATATTACAATTCTTTATTTAGTAGTGGTGACAATCCCCCACAAAGAAA





TTATGCACCAATGCCTACTCAGTTCATTGAGAGTGTCCCATACAAGCTCTGGCAAGCACACACAGATC





AATATCCCGAGATTTTTGAGGACTTCATCCCTCTATGGAACGGAAATGCCGCCATGACTGACATAGGA





ATGACAGCTTGTGTAGAATTCATCATCAATCGAGTCGGCCCAAGGACTTGCAGTTTAGTACATGTAGA





TTTGGAATCAAGTGCAAGCTTAAATCAACAATGCCTGTCAAAGCCGATAATTAATGCTATCATCACTG





CTACAACTGTTTTGTGCCCTCATGGGGTGCTTATTCTGAAATATAGTTGGTTGCCATTTACTAGATTTAG





TACTTTGATCACTTTCTTATGGTGCTACTTTGAGAGAATCACTGTTCTTAGGAGCACATATTCTGGTCCA





GCTAATCATGAGGTTTATTTAATTTGTATCCTTGCCAACAACTTTGCATTCCAGACTGTCTCGCAGGCA





ACAGGAATGGCGATGACTTTAACCGATCAAGGGTTTACTTTGATATCACCTGAAAGAATAAATCAGTA





TTGGGATGGTCACTTGAAGCAAGAACGTATCGTAGCAGAAGCAATTGATAAGGTGGTTCTAGGAGAA





GATGCTCTATTCAATTCGAGTGATAATGAATTAATTCTCAAATGTGGAGGGACACCAAATGCACGGAA





TCTTATCGATATCGAGCCAGTCGCAACTTTCATAGAATTTGAACAACTGATCTGCACAATGTTGACAAC





CCACTTGAAGGAAATAATTGATATAACAAGGTCTGGAACCCAGGATTATGAAAGTTTATTACTCACTC





CTTACAATTTAGGTCTTCTTGGTAAAATCAGTACGATAGTGAGATTATTAACAGAAAGGATTCTAAATC





ATACTATCAGGAATTGGTTGATCCTCCCACCTTCGCTCCGGATGATCGTGAAGCAGGACTTGGAATTCG





GCATATTCAGGATTACTTCCATCCTCAATTCTGATCGGTTCCTGAAGCTTTCTCCAAATAGGAAATACT





TGATTACACAATTAACTGCAGGCTACATTAGGAAATTGATTGAGGGGGATTGTAATATCGATCTAACC





AGACCTATCCAAAAACAAATCTGGAAAGCATTAGGTTGTGTAGTCTATTGTCACGATCCAGTAGATCA





AAGGGAATCAACAGAGTTTATTGATATAAATATTAATGAAGAAATAGACCGCGGGATCGATGGCGAG





GAAATCTAAATATATCAAGAATCAGAATTAGTTTAAGAAAAAAGAAGAGGATTAATCTTGGTTTTCCC





CTTGGT






9. CVL55


The nucleic acid sequence for CVL55 is:










(SEQ ID NO:69)



ACCAGGGGGAAAACGAAGTGGTGACTCAAATCATCGAAGACCCTCGAGATTACATAGGTCCGGAACC






TATGGCCTTCGTGACCGACCTCGAGTCAGAGTAGTTCAATAAGGACCTATCAAGTTTGGGCAATTTTTC





GTCCCCGACACAAAAATGTCATCCGTGCTTAAAGCATATGAGCGATTCACACTCACTCAAGAACTGCA





AGATCAGAGTGAGGAAGGTACAATCCCACCTACAACACTAAAACCGGTAATCAGGGTATTTATACTAA





CCTCTAATAACCCAGAGCTAAGATCCCGGCTTCTTCTATTCTGCCTACGGATTGTTCTCAGTAATGGTG





CAAGGGATTCCCATCGCTTTGGAGCATTACTTACAATGTTTTCGCTACCATCAGCCACAATGCTCAATC





ATGTCAAATTAGCTGACCAGTCACCAGAAGCTGATATCGAAAGGGTAGAGATCGATGGCTTTGAGGA





GGGATCATTCCGCTTAATCCCCAATGCTCGTTCAGGTATGAGCCGTGGAGAGATCAATGCCTATGCTG





CACTTGCAGAAGATCTACCTGACACACTAAACCATGCAACACCTTTTGTTGATTCCGAAGTCGAGGGA





ACTGCATGGGATGAGATTGAGACTTTCTTAGATATGTGTTACAGTGTCCTAATGCAGGCATGGATAGT





GACTTGCAAGTGCATGACTGCGCCAGACCAACCTGCTGCTTCTATTGAGAAACGCCTGCAAAAATATC





GTCAGCAAGGCAGGATCAACCCGAGATATCTCCTGCAACCGGAGGCTCGAAGAATAATCCAGAATGT





AATCCGAAAGGGAATGGTGGTCAGACATTTCCTCACCTTTGAACTGCAGCTTGCCCGAGCACAAAGCC





TTGTATCAAATAGGTATTATGCTATGGTAGGGGATGTTGGAAAGTATATAGAGAATTGTGGAATGGGA





GGCTTCTTTTTGACACTAAAATATGCATTAGGAACCAGATGGCCCACACTTGCTTTAGCTGCATTTTCA





GGAGAGCTAACAAAGCTAAAGTCCCTCATGGCATTATACCAGACCCTTGGTGAGCAGGCCCGATATTT





GGCCCTATTGGAGTCACCACATTTGATGGATTTTGCTGCAGCAAACTACCCACTGCTATATAGCTATGC





TATGGGAATAGGCTATGTGTTAGATGTCAACATGAGGAACTACGCTTTCTCCAGATCATACATGAATA





AGACATATTTCCAATTGGGAATGGAAACTGCAAGAAAACAACAGGGTGCAGTTGACATGAGGATGGC





AGAAGATCTCGGTCTAACTCAAGCCGAACGCACCGAGATGGCAAATACACTTGCCAAATTGACCACA





GCAAATCGAGGGGCAGACACCAGGGGAGGAGTCAACCCGTTCTCATCTATCACTGGGACAACTCAGG





TGCCCGCTGCAGCAACAGGTGACACATTCGAGAGTTACATGGCAGCGGATCGACTGAGGCAGAGATA





TGCTGATGCAGGCACCCACGATGATGAGATGCCACCATTGGAAGAGGAGGAAGAGGACGACACATCT





GCAGGTCCACGCACTGGACTAACTCTTGAACAAGTGGCCTTGGACATCCAGAACGCAGCAGTTGGAGC





TCCCATCCATACAGATGACCTGAATGCCGCACTGGGTGATCTTGACATCTAGACAATTCAGATCCCAA





TCTTAAATCGACACACCTAATTGACCAGTTAGATGGAACTACAGTGGATTCCATAAGGTTCCTGCCTAC





CATCGGCTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCCGATGCCAATAACA





CAATCCACAATCTACAATGGATCCCACTGATCTGAGCTTCTCCCCAGATGAGATCAATAAGCTCATAG





AGACAGGCCTGAATACTGTGGAGTATTTTACTTCCCAACAAGTCACAGGAACATCCTCTCTTGGAAAG





AATACAATACCACCAGGGGTCACAGGACTACTAACCAATGCTGCAGAGGCAAAGATCCAAGAGTCAA





CCAACCATCAGAAGGGTTCAGTTGGTGGGGGCGCAAAACCAAAGAAACCGCGACCAAAAATTGCCAT





TGTGCCAGCAGATGACAAAACGGTGCCCGGAAAGCCGATCCCAAACCCTCTATTAGGTCTGGACTCCA





CCCCGAGCACCCAAACTGTGCTTGATCTAAGTGGGAAAACATTACCATCAGGATCCTATAAGGGGGTT





AAACTTGCGAAATTTGGAAAAGAAAATCTGATGACACGGTTCATCGAGGAACCCAGAGAGAATCCTA





TCGCAACCAATTTCCCCATCGATTTTAAGAGGGGCAGGGATACCGGCGGGTTCCATAGAAGGGAGTAC





TCAATCGGATGGGTGGGAGATGAAGTCAAGGTCACTGAGTGGTGCAATCCATCCTGTTCTCCAATCAC





CGCTGCAGCAAGGCGATTTGAATGCACTTGTCACCAGTGTCCAGTCACTTGCTCTGAATGTGAACGAG





ATACTTAATACAGTGAGAAATTTGGACTCTCGGATGAATCAACTGGAGACAAAAGTAGATCGCATTCT





CTCATCTCAGTCTCTAATCCAGACCATCAAGAATGACATAGTTGGACTTAAAGCAGGGATGGCTACTT





TAGAAGGAATGATTACAACTGTGAAAATCATGGACCCGGGAGTTCCCAGTAATGTTACTGTGGAAGAT





GTACGCAAGAAACTAAGTAACCATGCTGTTGTTGTGCCAGAATCATTCAATGATgccTTCTTGACTCAAT





CTGAAGATGTAATTTCACTTGATGAGTTGGCTCGACCAACTGCAACAAGTGTTAAGAAGATTGTCAGG





AAGGTTCCTCCTCAGAAGGATCTGACTGGATTGAAGATCACACTAGAGCAATTGGCAAAGGATTGCAT





CAGCAAACCGAAGATGAGGGAAGAGTATCTCCTCAAAATCAACCAGGCTTCCAGTGAGGCTCAGCTA





ATTGACCTCAAGAAAGCAATCATCCGCAGTGCAATTTGATCAAGAAACACCCAATTACACTACACTGG





TATGACACTGTACTAACCCTGAGGGTTTTAGAAAAAACGATTAACGATAAATAAGCCCGAACACTACA





CACCACCCGAGGCAGCCATGCCATCCATCAGCATCCCCGCAGACCCCACCAATCCACGTCAATCAATA





AAAGCGTTCCCAATTGTGATCAACCGTGATGGGGGTGAGAAAGGTCGCTTGGTTAAACAACTACGCAC





AACCTACTTGAATGACCTAGATACTCATGAGCCACTGGTGACATTCGTAAATACTTATGGATTCATCTA





CGAACAGGATCGGGGAAATACCATTGTCGGAGAGGATCAACATGGGAAGAAAAGAGAGGCTGTGACT





GCTGCAATGGTTACCCTTGGATGTGGGCCTAATCTACCATCATTAGGGAATGTCCTGGGACAACTGAG





TGAATTCCAGGTCATTGTTAGGAAGACATCCAGCAAAGCGGAAGAGATGGTCTTTGAAATTGTTAAGT





ATCCGAGAATATTTCGGGGTCATACATTAATCCAGAAAGGACTAGTCTGTGTCTCCGCAGAAAAATTT





GTTAAGTCACCAGGGAAAGTACAATCTGGAATGGACTATCTCTTCATTCCGACATTTCTGTCAGTGACT





TACTGTCCAGCTGCAATCAAATTTCAGGTACCTGGCCCCATGTTGAAAATGAGATCAAGATACACTCA





GAGCTTACAACTTGAACTAATGATAAGAATCCTGTGTAAGCCCGATTCGCCACTTATGAAGGTCCATA





TCCCTGACAAGGAAGGAAGAGGATGTCTTGTATCAGTATGGTTGCATGTATGCAATATCTTCAAATCA





GGAAACAAGAATGGCAGTGAGTGGCAGGAATACTGGATGAGAAAGTGTGCTAACATGCAACTTGAAG





TGTCGATTGCAGATATGTGGGGACCAACTATCATAATTCATGCCAGAGGTCACATTCCCAAAAGTGCT





AAGTTGTTTTTTGGAAAGGGTGGATGGAGCTGCCATCCACTTCACGAAGTTGTTCCAAGTGTCACTAA





AACACTATGGTCCGTGGGCTGTGAGATTACAAAGGCGAAGGCAATAATACAAGAGAGTAGCATCTCT





CTTCTCGTGGAGACTACTGACATCATAAGTCCAAAAGTCAAAATTTCATCTAAGCATCGCCGCTTTGGG





AAATCAAATTGGGGTCTGTTCAAGAAAACCAAATCACTGCCCAACCTGACGGAGCTGGAATGACTGAC





CCCCAATCGAGACTACACCACCTCAAACTATAGGTGGGTGGTACCTCAGTGATTAATCTCGTAAGCAC





TGATCGTAGGCTACAACACACTAATATTATCCAGATTAGAGAGCTTAATTAGCTCTGTATTAATAATAA





CACTACTATTCCAATAACTGGAATCACCAGCTTGATTTATCTCCAAAATGATTCAAAGAAAACAAATC





ATATTAAGACTATCCTAAGCACGAACCCATATCGTCCTTCAAATCATGGGTACTATAATTCAATTTCTG





GTGGTCTCCTGTCTATTGGCAGGAGCAGGCAGTCTTGATCCAGCAGCCCTCATGCAAATCGGTGTCATT





CCAACAAATGTCCGGCAACTTATGTATTATACTGAGGCCTCATCAGCATTCATTGTTGTGAAGTTAATG





CCTACAATTGACTCGCCGATTAGTGGATGTAATATAACATCAATTTCAAGCTATAATGCAACAGTGAC





AAAACTCCTACAGCCGATCGGTGAGAATTTGGAGACGATTAGGAACCAGTTGATTCCAACTCGGAGGA





GACGCCGGTTTGCAGGGGTGGTGATTGGATTAGCTGCATTAGGAGTAGCTACTGCCGCACAGGTCACT





GCCGCAGTAGCACTAGTAAAGGCAAATGAAAATGCTGCGGCTATACTCAATCTCAAAAATGCAATCCA





AAAAACAAATGCAGCAGTTGCAGATGTGGTCCAGGCCACACAATCACTAGGAACaGCAGTTCAAGCA





GTTCAAGATCACATAAACAGTGTGGTAAGTCCAGCAATTACAGCAGCCAATTGTAAAGCCCAAGATGC





TATCATTGGCTCAATCCTCAATCTCTATTTGACCGAGTTGACAACTATCTTCCACAATCAAATTACAAA





CCCTGCATTGAGTCCTATTACAATTCAAGCTTTAAGGATCCTACTAGGGAGTACCTTGCCGACTGTGGT





CGAAAAATCTTTCAATACCCAGATAAGTGCGGCTGAGCTTCTCTCATCAGGGTTATTGACAGGCCAGA





TTGTGGGATTAGATTTGACCTATATGCAGATGGTCATAAAAATTGAGCTGCCAACTTTAACTGTACAAC





CTGCAACCCAGATCATAGATCTGGCCACCATTTCTGCATTCATTAACAATCAAGAAGTCATGGCCCAA





TTACCAACACGTGTTATTGTGACTGGCAGCTTGATCCAAGCCTATCCCGCATCGCAATGCACTATTACA





CCCAACACTGTGTACTGTAGGTATAATGATGCCCAAGTACTCTCAGATGATACGATGGCTTGCCTCCA





AGGTAACTTGACAAGATGCACCTTCTCTCCAGTGGTTGGGAGCTTTCTCACTCGATTCGTGCTGTTCGA





TGGAATAGTTTATGCAAATTGCAGGTCGATGTTGTGCAAGTGCATGCAGCCTGCTGCTGTGATCCTACA





GCCGAGTTCATCCCCTGTAACTGTCATTGACATGTACAAATGTGTGAGTCTGCAGCTTGACAATCTCAG





ATTCACCATCACTCAATTGGCCAATGTAACCTACAATAGCACCATCAAGCTTGAAACATCCCAGATCTT





GCCTATTGATCCGTTGGATATATCCCAGAATCTAGCTGCGGTGAATAAGAGTCTAAGTGATGCACTAC





AACACTTAGCACAAAGTGACACATACCTTTCTGCAATCACATCAGCTACGACTACAAGTGTATTATCC





ATAATAGCAATCTGTCTTGGATCGTTAGGTTTAATATTAATAATCTTGCTCAGTGTAGTTGTGTGGAAG





TTATTGACCATTGTCGCTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAATTCAGCATTCCAC





CACTCACGATCTGATCTCAGTGAGAAAAATCAACCTGCAACTCTTGGAACAAGATAAGACAGTCATCC





ATTAGTAATTTTTAAGAAAAAAACGATAGGACCGAAACTAGTATTGAAAGAACCGTCTCGGTCAATCT





AGGTAATCGAGCTGcTACCGTCTCGGAAAGCTCAAATCATGCTGCCTGATCCGGAAGATCCGGAAAGC





AAAAAAGCTACAAGGAGAACAGGAAACCTAATTATCTGCTTCCTATTCATCTTCTTTCCGTTTGTAAAC





TTCATTGTTCCAACTCTAAGACACTTGCTGTCCTAACACCTGCTATAGGCTATCCACTGCATCATCTCTT





TTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCCGGTGCCAACAACACAATCCAC





AATCTACAGTCGACGCGGCCGCCACCatgttcgtgttcctggtgctgctgccactggtcagcagccagtg





cgtgaatttcactacccggacccagctgcctcctgcttatacaaacagcttcaccaggggagtgtactaccccg





ataaggtgttccgcagctctgtgctgcacagcacccaggacttgtttcttcccttcttcagcaacgtgac





ctggttccacgccatccacgtgtccggcaccaacggcaccaaaagattcgccaatcctgtgctgcctttcaacgat





ggcgtgtactttgcctctacagagaagtctaacatcatcagaggctggatcttcggcacaaccctggattct





aaaacccagagcctgctgatcgtgaacaatgccaccaatgtagtgatcaaggtttgtgagttccagttct





gcaacgacccctttctgggcgtttactaccacaagaacaacaaaagctggatggaaagcgagtt





cagggtgtactctagcgccaacaactgtaccttcgagtacgtgagccagccttttctgatggacctggaggg





caagcagggcaacttcaaaaacctgcgggagttcgtgtttaagaacatcgacggatacttcaagatt





tactccaagcacaccccaattaacttggttagaggactgccccaaggcttcagcgccctggaacccctggt





ggacctgcctatcggcatcaacatcacaagattccaaaccctgcatagaagctatctgacaccaggcgactctagc





tctggatggacagccggcgccgctgcttattacgtgggctacctgcagcctagaaccttcctcctg





aaatacaacgagaacggaaccatcaccgacgccgtggactgcgccctggatcctctgagcgagacaaagtgcac





cctgaagtccttcaccgtcgaaaagggcatctaccaaacaagcaacttcagagtgcagcctactgagagcatcgtg





cggtttccaaacatcaccaacctgtgtccttttggcgaggtgttcaacgccacccggttcgcttccgtgt





acgcctggaatagaaagcggatcagcaactgcgtggccgactacagcgtgctgtata





atagcgcctcattttctacttttaaatgttacggcgtgtctcctacaaagctgaacgatc





tgtgcttcacaaatgtgtacgccgatagcttcgtgattagaggcgacgaggtgcggcagatcgc





ccctggccagaccggcaacatcgctgactacaactacaagctgcctgacgacttcaccggct





gtgtgatcgcatggaacagcaataacctggactctaaggtgggcggaaactacaattacctgtaca





gactgttcagaaagagcaacctgaagcccttcgagagagatatctccacagaaatctatca





gccggatctacaccttgtaatggcgtgaagggcttcaactgctacttccctctgcaatc





ctacgggctttcagcccacatacggcgtgggctaccagccataccgggtcgtggtgctg





agcttcgagctgctgcacgcccctgccacagtgtgcggccctaagaagagcaccaatctggtaa





agaacaagtgcgtcaacttcaatttcaacggcctgaccgggaccggagtgctgaccgaaagcaa





caagaaattcctgccgttccagcagttcggcagagatatcgccgacaccaccgatgccgtgcg





ggacccccagacacttgaaatcctggacatcaccccttgcagttttggcggcgtgtccgtgat





cacacctggaacaaacaccagcaaccaggtggccgtgctgtaccagggcgtcaactgcaccgaggtccccgt





ggccatccacgccgatcagctgacacctacatggcgggtgtactctaccggcagcaacgtgttcc





aaaccagagccggctgcctgatcggcgctgagcacgtgaacaacagctacgagtgcgacattcctatcggt





gctggcatctgcgcctcttaccagacacagacaaacagccccagaagagcgagaagcgtggctagtcagagca





tcatcgcctacaccatgagcctgggcgtggagaacagcgtggcctactctaacaatagcatcgccatcccaacca





acttcacaatctctgtgaccacagagatcctgcccgtgtccatgaccaagacatctgtggactgcacaatgtata





tctgtggcgattctaccgagtgcagcaacctgctgctccagtacggcagcttttgtacccagctgaatagagcc





ctgacaggcatcgccgtggagcaggataagaacacacaggaggtgttcgcccaggtga





agcaaatctacaagaccccccctatcaaggactttggcggcttcaatttttc





ccagatcctgcctgatccatccaagccttctaagcggagcttta





tcgaggacctgctgttcaacaaggtgaccctggccgatgccggcttcatc





aagcagtatggcgattgcctgggcgacatcgcagccagggacctgatctgcgc





ccagaagtttaatggcctgaccgtgctgccacccctgctgacagatgagatgatcg





cacagtacacaagcgccctgctggccggcaccatcacatccggatggacctt





cggcgcaggagccgccctccagatcccctttgccatgcagatggcctataggttcaa





cggcatcggcgtgacccagaatgtgctgtacgagaaccagaagctgatcgccaa





tcagtttaactccgccatcggcaagatccaggacagcctgtcctctacagccagc





gccctgggcaagctccaggatgtggtgaatcagaacgcccaggccctgaataccctgg





tgaagcagctgagcagcaacttcggcgccatctctagcgtgctgaatgac





atcctgagccggctggacaaggtggaggcagaggtgcagatcgaccggctgatcacc





ggccggctccagagcctccagacctatgtgacacagcagctgatcaggg





ccgccgagatcagggccagcgccaatctggcagcaaccaagatgtccgagtgcgtgct





gggccagtctaagagagtggacttttgtggcaagggctatcacctgatgt





ccttccctcagtctgccccacacggcgtggtgtttctgcacgtgacctacgtgccc





gcccaggagaagaacttcaccacagcccctgccatctgccacgatggcaaggc





ccactttccaagggagggcgtgttcgtgtccaacggcacccactggtttgtgacacag





cgcaatttctacgagccccagatcatcaccacagacaacaccttcgtgagcg





gcaactgtgacgtggtcatcggcatcgtgaacaataccgtgtatgatccactccagc





ccgagctggacagctttaaggaggagctggataagtatttcaagaatcacacct





cccctgacgtggatctgggcgacatcagcggcatcaatgcctccgtggtgaacatc





cagaaggagatcgaccgcctgaacgaggtggctaagaatctgaacgagagc





ctgatcgacctccaggagctgggcaagtatgagcagtacatcaagtggccctggta





catctggctgggcttcatcgccggcctgatcgccatcgtgatggtgaccatcat





gctgtgctgtatgacatcctgctgttcttgcctgaagggctgctgtagctgt





ggctcctgctgtAAGTTATTGACCATTGTCGTTGCTAATCGAA





ATAGAATGGAGAATTTTGTTTATCATAAATGAACGCGTGCTAGCCTCCTGCCATACTTCCTACTCACAT





CATATCTATTTTAAAGAAAAAATAGGCCCGAACACTAATCGTGCCGGCAGTGCCACTGCACACACAAC





ACTACACATACAATACACTACAATGGTTGCAGAAGATGCCCCTGTTAGGGGCACTTGCCGAGTATTAT





TTCGAACAACAACTTTAATTTTTCTATGCACACTATTAGCATTAAGCATCTCTATCCTTTATGAGAGTTT





AATAACCCAAAAGCAAATCATGAGCCAAGCAGGCTCAACTGGATCTAATTCTAGATTAGGAAGTATCA





CTGATCTTCTTAATAATATTCTCTCTGTCGCAAATCAGATTATATATAACTCTGCAGTCGCTCTACCTCT





ACAATTGGACACTCTTGAATCAACACTCCTTACAGCCATTAAGTCTCTTCAAACAAGTGACAAGCTAG





AACAGAACTGCTCGTGGGGTGCTGCACTGATTAATGATAATAGATACATTAATGGCATCAATCAGTTC





TATTTCTCAATTGCTGAGGGTCGCAAGCTGACACTTGGCCCACTTCTTAATATACCTAGTTTCATTCCA





ACTGCCACGACACCAGAGGGCTGCACCAGGATCCCATCATTCTCGCTCACCAAGACACACTGGTGTTA





TACACACAATGTTATCCTGAATGGATGCCAGGATCATGTATCCTCAAATCAATTTGTTTCCATGGGAAT





CATTGAACCCACTTCTGCCGGGTTTCCATCCTTTCGAACCCTAAAGACTCTATATCTCAGCGATGGGGT





CAATCGTAAGAGCTGCTCTATCAGTACAGTTCCGGGGGGTTGTATGATGTACTGTTTCGTCTCTACTCA





ACCAGAGAGGGATGACTACTTTTCTACCGCTCCTCCAGAACAACGAATTATTATAATGTACTATAATG





ATACAATCGTGGAGCGCATAATTAATCCACCCGGGGTACTAGATGTATGGGCAACATTGAACCCAGGA





ACAGGAAGCGGGGTATATTATTTAGGTTGGGTACTCTTTCCAATATATGGCGGCGTGATTAAAGATAC





GAGTTTATGGAATAATCAAGCAAATAAATACTTTATCCCCCAGATGGTTGCTGCTCTCTGCTCACAAAA





CCAGGCAACTCAAGTCCAAAATGCTAAGTCATCATACTATAGCAGCTGGTTTGGCAATCGAATGATTC





AGTCTGGGATCCTGGCATGTCCTCTTCAACAGGATCTAACCAATGAGTGTTTAGTTCTGCCCTTTTCTA





ATGATCAGGTGCTTATGGGTGCTGAAGGGAGATTATACATGTATGGTGACTCGGTGTATTACTACCAA





AGAAGCAATAGTTGGTGGCCTATGACCATGCTGTATAAGGTAACCATAACATTCACTAATGGTCAGCC





ATCTGCTATATCAGCTCAGAATGTGCCCACACAGCAGGTCCCTAGACCTGGGACAGGAAGCTGCTCTG





CAACAAATAGATGTCCCGGTTTTTGCTTGAAAGGAGTGTATGCTGATGCCTGGTTACTGACCAACCCTT





CGTCTACCAGTACATTTGGATCAGAAGCAACCTTCACTGGTTCTTATCTCAACGCAGCAACTCAGCGTA





TCAATCCGACGATGTATATCGCGAACAACACACAGATCATAAGCTCACAGCAATTTGGATCAAGCGGT





CAAGAAGCAGCATATGGCCACACAACTTGTTTTAGGGACACAGGCTCTGTTATGGTATACTGTATCTA





TATTATTGAATTGTCCTCATCTCTCTTAGGACAATTTCAGATTGTCCCATTTATCCGTCAGGTGACACTA





TCCTAAAGGCAGAAGCCTCCAGGTCTGACCCAGCCAATCAAAGCATTATACCAGACCATGGAATGCAT





ACCAAACATTATTGACACTAATGACACACAAAATTGGTTTTAAGAAAAACCAAGAGAACAATAGGCC





AGAATGGCTGGGTCTCGGGAGATATTACTCCCTGAAGTCCATCTCAATTCACCAATTGTAAAGCATAA





GCTATACTATTACATTCTACTTGGAAACCTCCCAAATGAGATCGACATTGACGATTTAGGTCCATTACA





TAATCAAAATTGGAATCAAATAGCACATGAAGAGTCTAACTTAGCCCAACGCTTGGTAAATGTAAGAA





ATTTTCTAATTACCCACATCCCTGATCTTAGAAAGGGCCATTGGCAAGAGTATGTCAATGTAATACTGT





GGCCGCGAATTCTTCCCTTGATCCCGGATTTTAAAATCAATGACCAATTGCCTCTACTCAAAAATTGGG





ACAAGTTAGTTAAAGAATCATGTTCAGTAATCAATGCGGGTACTTCCCAGTGCATTCAGAATCTCAGC





TATGGACTGACAGGTCGTGGGAACCTCTTTACACGATCACGTGAACTCTCTGGTGACCGCAGGGATAT





TGATCTTAAGACGGTTGTGGCAGCATGGCATGACTCAGACTGGAAAAGAATAAGTGATTTTTGGATTA





TGATCAAATTCCAGATGAGACAATTAATTGTTAGGCAAACAGATCATAATGATCCTGATTTAATCACG





TATATCGAAAATAGAGAAGGCATAATCATCATAACCCCTGAACTGGTAGCATTATTTAACACTGAGAA





TCATACACTAACATACATGACCTTTGAAATTGTACTGATGGTTTCAGATATGTACGAAGGTCGTCACAA





CATTTTATCACTATGCACAGTTAGCACTTACCTGAATCCTCTGAAGAAAAGAATAACATATTTATTGAG





CCTTGTAGATAACTTAGCTTTTCAGATAGGTGATGCTGTATATAACATAATTGCTTTGCTAGAATCCTT





TGTATATGCACAGTTGCAAATGTCAGATCCCATCCCAGAACTCAGAGGACAATTCCATGCATTCGTAT





GTTCTGAGATTCTTGATGCACTAAGGGGAACTAATAGTTTCACCCAGGATGAATCAAGAACTGTGACA





ACCAATTTGATATCCCCATTCCAAGATCTGACCCCAGATCTTACGGCTGAATTGCTCTGTATAATGAGG





CTTTGGGGACACCCCATGCTCACCGCCAGTCAAGCTGCGGGAAAGGTACGCGAGTCCATGTGTGCTGG





AAAAGTATTAGACTTTCCCACCATTATGAAAACACTAGCCTTTTTCCATACTATTCTGATCAATGGATA





CAGGAGGAAGCATCATGGAGTATGGCCACCCTTAAACTTACCGGGTAATGCTTCAAAGGGTCTCACGG





AACTTATGAATGACAATACTGAGATAAGCTATGAATTCACACTTAAGCATTGGAAGGAAATCTCTCTT





ATAAAATTCAAGAAATGTTTTGATGCAGACGCAGGTGAGGAACTCAGTATATTTATGAAAGATAAAGC





AATTAGTGCCCCAAAACAAGATTGGATGAGTGTGTTTAGAAGAAGCCTAATCAAACAGCGCCATCAGC





ATCATCAGGTCCCCCTACCAAATCCATTCAATCGACGGCTATTGCTAAACTTTCTCGGAGATGACAAAT





TCGACCCGAATGTGGAGCTACAGTATGTAACATCAGGTGAGTATCTACATGATGACACGTTTTGTGCA





TCATATTCACTAAAAGAGAAGGAAATTAAACCTGATGGTCGAATTTTTGCAAAGTTGACTAAGAGAAT





GAGATCATGTCAAGTTATAGCAGAATCTCTTTTAGCGAACCATGCTGGGAAGTTAATGAAAGAGAATG





GTGTTGTGATGAATCAGCTATCATTAACAAAATCACTATTAACAATGAGTCAGATTGGAATAATATCC





GAGAAAGCTAGAAAATCGACTCGAGATAACATAAATCAACCTGGTTTCCAGAATATCCAGAGAAATA





AATCACATCACTCCAAGCAAGTCAATCAGCGAGATCCAAGTGATGACTTTGAATTGGCAGCATCTTTT





TTAACTACTGATCTCAAAAAATATTGTTTACAATGGAGGTACCAGACAATTATCCCATTTGCTCAATCA





TTAAACAGAATGTATGGTTATCCTCATCTCTTTGAGTGGATTCACTTACGGCTAATGCGTAGTACACTT





TACGTGGGGGATCCCTTCAACCCACCAGCAGATACCAGTCAATTTGATCTAGATAAAGTAATTAATGG





AGATATCTTCATTGTATCACCCAGAGGTGGAATTGAAGGGCTATGTCAAAAGGCTTGGACAATGATAT





CTATCTCTGTGATAATTCTATCTGCCACAGAGTCTGGCACACGAGTAATGAGTATGGTGCAGGGAGAT





AATCAAGCAATTGCTGTCACCACACGAGTACCAAGGAGCCTGCCGACTCTTGAGAAAAAGACTATTGC





TTTTAGATCTTGTAATCTATTCTTTGAGAGGTTAAAATGTAATAATTTTGGATTAGGTCACCATTTGAA





AGAACAAGAGACTATCATTAGTTCTCACTTCTTTGTTTATAGCAAGAGAATATTCTATCAGGGGAGGA





TTCTAACGCAAGCCTTAAAAAATGCTAGTAAGCTCTGCTTGACAGCTGATGTCCTAGGAGAATGTACC





CAATCATCATGTTCTAATCTTGCAACTACTGTCATGAGGTTAACTGAGAATGGTGTTGAAAAAGATATC





TGTTTCTACTTGAATATCTATATGACCATCAAACAGCTCTCCTATGATATCATCTTCCCTCAAGTGTCAA





TTCCTGGAGATCAGATCACATTAGAATACATAAATAATCCACACCTGGTATCACGATTGGCTCTTCTGC





CATCCCAGCTAGGAGGTCTAAACTACCTGTCATGCAGTAGGCTGTTCAATCGAAACATAGGCGACCCG





GTGGTTTCCGCAGTTGCAGATCTTAAGAGATTAATTAAATCAGGATGTATGGATTACTGGATCCTTTAT





AACTTATTAGGGAGAAAACCGGGAAACGGCTCATGGGCTACTTTAGCAGCTGACCCGTACTCAATCAA





TATAGAGTATCAATACCCCCCAACTACAGCTCTTAAGAGGCACACCCAACAAGCTCTGATGGAACTCA





GTACGAATCCAATGTTACGTGGCATATTCTCTGACAATGCACAGGCAGAAGAAAATAATCTTGCTAGA





TTTCTCCTGGATAGGGAGGTGATCTTTCCGCGTGTAGCTCACATCATCATTGAGCAAACCAGTGTCGGG





AGGAGAAAACAGATTCAAGGATATTTGGATTCAACTAGATCGATAATGAGTAAATCACTAGAAATTA





AGCCCTTGTCCAATAGGAAGCTTAATGAAATACTGGATTACAACATCAATTACCTAGCTTACAATTTG





GCATTACTCAAGAATGCTATTGAACCTCCGACTTATTTGAAAGCAATGACTCTTGAAACATGTAGCATC





GACATTGCAAGGAGCCTCCGGAAGCTCTCCTGGGCCCCACTCTTGGGTGGGAGAAATCTTGAAGGATT





AGAGACGCCAGATCCCATTGAAATTACTGCAGGAGCATTAATTGTTGGATCGGGCTACTGTGAACAGT





GTGCTGCAGGAGACAATCGATTCACATGGTTTTTCTTGCCATCTGGTATCGAGATAGGAGGGGATCCC





CGTGATAATCCTCCTATCCGTGTACCGTACATTGGCTCCAGGACTGATGAGAGGAGGGTAGCCTCAAT





GGCATACATCAGGGGTGCCTCGAGTAGCCTAAAAGCAGTTCTTAGACTGGCGGGAGTGTACATCTGGG





CATTCGGAGATACTCTGGAGAATTGGATAGATGCACTGGATTTGTCTCACACTAGAGTTAACATCACA





CTTGAACAGCTGCAATCCCTCACCCCACTTCCAACCTCTGCCAATCTAACCCATCGGTTGGATGATGGC





ACAACTACCCTAAAGTTTACTCCTGCGAGCTCTTACACCTTTTCAAGTTTCACTCATATATCAAATGAT





GAGCAATACCTGACAATTAATGACAAAACTGCAGATTCAAATATAATCTACCAACAGTTAATGATCAC





TGGACTCGGAATTTTAGAAACATGGAATAATCCCCCAATCAATAGAACATTCGAAGAATCTACCCTAC





ATTTGCACACTGGTGCATCATGTTGTGTCCGACCTGTGGACTCCTGCATCATCTCAGAAGCATTAACAG





TCAAGCCACATATTACAGTACCGTACAGCAATAAATTTGTATTTGATGAAGACCCGCTATCTGAATAT





GAGACTGCAAAACTGGAATCGTTATCATTTCAAGCCCAATTAGGCAACATTGATGCTGTAGATATGAC





AGGTAAATTAACATTATTGTCCCAATTCACTGCAAGGCAGATTATTAATGCAATCACTGGACTCGATG





AGTCTGTCTCTCTTACTAATGATGCCATTGTTGCATCAGACTATGTCTCCAATTGGATTAGTGAATGCA





TGTATACCAAATTAGATGAATTATTTATGTATTGTGGGTGGGAACTACTATTGGAACTATCCTATCAAA





TGTATTATCTGAGGGTAGTTGGGTGGAGTAATATAGTGGATTATTCTTACATGATCTTGAGAAGAATCC





CGGGTGCAGCATTAAACAATCTGGCATCTACATTAAGTCATCCAAAACTTTTCCGACGAGCTATCAAC





CTAGATATAGTTGCCCCCTTAAATGCTCCTCATTTTGCATCTCTGGACTACATCAAGATGAGTGTGGAT





GCAATACTCTGGGGCTGTAAAAGAGTCATCAATGTGCTCTCCAATGGAGGGGACTTAGAATTAGTTGT





GACATCTGAAGATAGCCTTATTCTCAGTGACCGATCCATGAATCTCATTGCAAGGAAATTAACTTTATT





ATCACTGATTCACCATAATGGTTTGGAACTACCAAAGATTAAGGGGTTCTCTCCTGATGAGAAGTGTTT





CGCTTTGACAGAATTTTTGAGGAAAGTGGTGAACTCAGGGTTGAGTTCAATAGAGAACCTATCAAATT





TTATGTACAATGTGGAGAACCCACGGCTTGCAGCATTCGCCAGCAACAATTACTACCTGACCAGAAAA





TTATTGAATTCAATACGAGATACTGAGTCGGGTCAAGTAGCAGTCACCTCATATTATGAATCATTAGA





ATATATTGATAGTCTTAAGCTAACCCCACATGTGCCTGGTACCTCATGCATTGAGGATGATAGTCTATG





TACAAATGATTACATAATCTGGATCATAGAGTCTAATGCAAACTTGGAGAAGTATCCAATTCCAAATA





GCCCTGAGGATGATTCCAATTTCCATAACTTTAAGTTGAATGCTCCATCGCACCATACCTTACGCCCAT





TAGGGTTGTCATCAACTGCTTGGTATAAGGGTATAAGCTGTTGCAGGTACCTTGAGCGATTAAAGCTA





CCACAAGGTGATCATTTATATATTGCAGAAGGTAGTGGTGCCAGTATGACAATCATAGAATACCTATT





CCCAGGAAGAAAGATATATTACAATTCTTTATTTAGTAGTGGTGACAATCCCCCACAAAGAAATTATG





CACCAATGCCTACTCAGTTCATTGAGAGTGTCCCATACAAGCTCTGGCAAGCACACACAGATCAATAT





CCCGAGATTTTTGAGGACTTCATCCCTCTATGGAACGGAAATGCCGCCATGACTGACATAGGAATGAC





AGCTTGTGTAGAATTCATCATCAATCGAGTCGGCCCAAGGACTTGCAGTTTAGTACATGTAGATTTGG





AATCAAGTGCAAGCTTAAATCAACAATGCCTGTCAAAGCCGATAATTAATGCTATCATCACTGCTACA





ACTGTTTTGTGCCCTCATGGGGTGCTTATTCTGAAATATAGTTGGTTGCCATTTACTAGATTTAGTACTT





TGATCACTTTCTTATGGTGCTACTTTGAGAGAATCACTGTTCTTAGGAGCACATATTCTGGTCCAGCTA





ATCATGAGGTTTATTTAATTTGTATCCTTGCCAACAACTTTGCATTCCAGACTGTCTCGCAGGCAACAG





GAATGGCGATGACTTTAACCGATCAAGGGTTTACTTTGATATCACCTGAAAGAATAAATCAGTATTGG





GATGGTCACTTGAAGCAAGAACGTATCGTAGCAGAAGCAATTGATAAGGTGGTTCTAGGAGAAGATG





CTCTATTCAATTCGAGTGATAATGAATTAATTCTCAAATGTGGAGGGACACCAAATGCACGGAATCTT





ATCGATATCGAGCCAGTCGCAACTTTCATAGAATTTGAACAACTGATCTGCACAATGTTGACAACCCA





CTTGAAGGAAATAATTGATATAACAAGGTCTGGAACCCAGGATTATGAAAGTTTATTACTCACTCCTT





ACAATTTAGGTCTTCTTGGTAAAATCAGTACGATAGTGAGATTATTAACAGAAAGGATTCTAAATCAT





ACTATCAGGAATTGGTTGATCCTCCCACCTTCGCTCCGGATGATCGTGAAGCAGGACTTGGAATTCGG





CATATTCAGGATTACTTCCATCCTCAATTCTGATCGGTTCCTGAAGCTTTCTCCAAATAGGAAATACTT





GATTACACAATTAACTGCAGGCTACATTAGGAAATTGATTGAGGGGGATTGTAATATCGATCTAACCA





GACCTATCCAAAAACAAATCTGGAAAGCATTAGGTTGTGTAGTCTATTGTCACGATCCAGTAGATCAA





AGGGAATCAACAGAGTTTATTGATATAAATATTAATGAAGAAATAGACCGCGGGATCGATGGCGAGG





AAATCTAAATATATCAAGAATCAGAATTAGTTTAAGAAAAAAGAAGAGGATTAATCTTGGTTTTCCCC





TTGGT.






10. CVL58


The nucleic acid sequence for CVL58 is:










(SEQ ID NO: 70)



ACCAGGGGGAAAACGAAGTGGTGACTCAAATCATCGAAGACCCTCGAGATTACATAGGTCCGGAACC






TATGGCCTTCGTGACCGACCTCGAGTCAGAGTAGTTCAATAAGGACCTATCAAGTTTGGGCAATTTTTC





GTCCCCGACACAAAAATGTCATCCGTGCTTAAAGCATATGAGCGATTCACACTCACTCAAGAACTGCA





AGATCAGAGTGAGGAAGGTACAATCCCACCTACAACACTAAAACCGGTAATCAGGGTATTTATACTAA





CCTCTAATAACCCAGAGCTAAGATCCCGGCTTCTTCTATTCTGCCTACGGATTGTTCTCAGTAATGGTG





CAAGGGATTCCCATCGCTTTGGAGCATTACTTACAATGTTTTCGCTACCATCAGCCACAATGCTCAATC





ATGTCAAATTAGCTGACCAGTCACCAGAAGCTGATATCGAAAGGGTAGAGATCGATGGCTTTGAGGA





GGGATCATTCCGCTTAATCCCCAATGCTCGTTCAGGTATGAGCCGTGGAGAGATCAATGCCTATGCTG





CACTTGCAGAAGATCTACCTGACACACTAAACCATGCAACACCTTTTGTTGATTCCGAAGTCGAGGGA





ACTGCATGGGATGAGATTGAGACTTTCTTAGATATGTGTTACAGTGTCCTAATGCAGGCATGGATAGT





GACTTGCAAGTGCATGACTGCGCCAGACCAACCTGCTGCTTCTATTGAGAAACGCCTGCAAAAATATC





GTCAGCAAGGCAGGATCAACCCGAGATATCTCCTGCAACCGGAGGCTCGAAGAATAATCCAGAATGT





AATCCGAAAGGGAATGGTGGTCAGACATTTCCTCACCTTTGAACTGCAGCTTGCCCGAGCACAAAGCC





TTGTATCAAATAGGTATTATGCTATGGTAGGGGATGTTGGAAAGTATATAGAGAATTGTGGAATGGGA





GGCTTCTTTTTGACACTAAAATATGCATTAGGAACCAGATGGCCCACACTTGCTTTAGCTGCATTTTCA





GGAGAGCTAACAAAGCTAAAGTCCCTCATGGCATTATACCAGACCCTTGGTGAGCAGGCCCGATATTT





GGCCCTATTGGAGTCACCACATTTGATGGATTTTGCTGCAGCAAACTACCCACTGCTATATAGCTATGC





TATGGGAATAGGCTATGTGTTAGATGTCAACATGAGGAACTACGCTTTCTCCAGATCATACATGAATA





AGACATATTTCCAATTGGGAATGGAAACTGCAAGAAAACAACAGGGTGCAGTTGACATGAGGATGGC





AGAAGATCTCGGTCTAACTCAAGCCGAACGCACCGAGATGGCAAATACACTTGCCAAATTGACCACA





GCAAATCGAGGGGCAGACACCAGGGGAGGAGTCAACCCGTTCTCATCTATCACTGGGACAACTCAGG





TGCCCGCTGCAGCAACAGGTGACACATTCGAGAGTTACATGGCAGCGGATCGACTGAGGCAGAGATA





TGCTGATGCAGGCACCCACGATGATGAGATGCCACCATTGGAAGAGGAGGAAGAGGACGACACATCT





GCAGGTCCACGCACTGGACTAACTCTTGAACAAGTGGCCTTGGACATCCAGAACGCAGCAGTTGGAGC





TCCCATCCATACAGATGACCTGAATGCCGCACTGGGTGATCTTGACATCTAGACAATTCAGATCCCAA





TCTTAAATCGACACACCTAATTGACCAGTTAGATGGAACTACAGTGGATTCCATAAGGTTCCTGCCTAC





CATCGGCTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCCGATGCCAATAACA





CAATCCACAATCTACAATGGATCCCACTGATCTGAGCTTCTCCCCAGATGAGATCAATAAGCTCATAG





AGACAGGCCTGAATACTGTGGAGTATTTTACTTCCCAACAAGTCACAGGAACATCCTCTCTTGGAAAG





AATACAATACCACCAGGGGTCACAGGACTACTAACCAATGCTGCAGAGGCAAAGATCCAAGAGTCAA





CCAACCATCAGAAGGGTTCAGTTGGTGGGGGCGCAAAACCAAAGAAACCGCGACCAAAAATTGCCAT





TGTGCCAGCAGATGACAAAACGGTGCCCGGAAAGCCGATCCCAAACCCTCTATTAGGTCTGGACTCCA





CCCCGAGCACCCAAACTGTGCTTGATCTAAGTGGGAAAACATTACCATCAGGATCCTATAAGGGGGTT





AAACTTGCGAAATTTGGAAAAGAAAATCTGATGACACGGTTCATCGAGGAACCCAGAGAGAATCCTA





TCGCAACCAATTCCCCCATCGATTTTAAGAGGGGCAGGGATACCGGCGGGTTCCATAGAAGGGAGTAC





TCAATCGGATGGGTGGGAGATGAAGTCAAGGTCACTGAGTGGTGCAATCCATCCTGTTCTCCAATCAC





CGCTGCAGCAAGGCGATTTGAATGCACTTGTCACCAGTGTCCAGTCACTTGCTCTGAATGTGAACGAG





ATACTTAATACAGTGAGAAATTTGGACTCTCGGATGAATCAACTGGAGACAAAAGTAGATCGCATTCT





CTCATCTCAGTCTCTAATCCAGACCATCAAGAATGACATAGTTGGACTTAAAGCAGGGATGGCTACTT





TAGAAGGAATGATTACAACTGTGAAAATCATGGACCCGGGAGTTCCCAGTAATGTTACTGTGGAAGAT





GTACGCAAGAAACTAAGTAACCATGCTGTTGTTGTGCCAGAATCATTCAATGATAGTTTCTTGACTCAA





TCTGAAGATGTAATTTCACTTGATGAGTTGGCTCGACCAACTGCAACAAGTGTTAAGAAGATTGTCAG





GAAGGTTCCTCCTCAGAAGGATCTGACTGGATTGAAGATCACACTAGAGCAATTGGCAAAGGATTGCA





TCAGCAAACCGAAGATGAGGGAAGAGTATCTCCTCAAAATCAACCAGGCTTCCAGTGAGGCTCAGCT





AATTGACCTCAAGAAAGCAATCATCCGCAGTGCAATTTGATCAAGAAACACCCAATTACACTACACTG





GTATGACACTGTACTAACCCTGAGGGTTTTAGAAAAAACGATTAACGATAAATAAGCCCGAACACTAC





ACACCACCCGAGGCAGCCATGCCATCCATCAGCATCCCCGCAGACCCCACCAATCCACGTCAATCAAT





AAAAGCGTTCCCAATTGTGATCAACCGTGATGGGGGTGAGAAAGGTCGCTTGGTTAAACAACTACGCA





CAACCTACTTGAATGACCTAGATACTCATGAGCCACTGGTGACATTCGTAAATACTTATGGATTCATCT





ACGAACAGGATCGGGGAAATACCATTGTCGGAGAGGATCAACATGGGAAGAAAAGAGAGGCTGTGA





CTGCTGCAATGGTTACCCTTGGATGTGGGCCTAATCTACCATCATTAGGGAATGTCCTGGGACAACTG





AGTGAATTCCAGGTCATTGTTAGGAAGACATCCAGCAAAGCGGAAGAGATGGTCTTTGAAATTGTTAA





GTATCCGAGAATATTTCGGGGTCATACATTAATCCAGAAAGGACTAGTCTGTGTCTCCGCAGAAAAAT





TTGTTAAGTCACCAGGGAAAGTACAATCTGGAATGGACTATCTCTTCATTCCGACATTTCTGTCAGTGA





CTTACTGTCCAGCTGCAATCAAATTTCAGGTACCTGGCCCCATGTTGAAAATGAGATCAAGATACACT





CAGAGCTTACAACTTGAACTAATGATAAGAATCCTGTGTAAGCCCGATTCGCCACTTATGAAGGTCCA





TATCCCTGACAAGGAAGGAAGAGGATGTCTTGTATCAGTATGGTTGCATGTATGCAATATCTTCAAAT





CAGGAAACAAGAATGGCAGTGAGTGGCAGGAATACTGGATGAGAAAGTGTGCTAACATGCAACTTGA





AGTGTCGATTGCAGATATGTGGGGACCAACTATCATAATTCATGCCAGAGGTCACATTCCCAAAAGTG





CTAAGTTGTTTTTTGGAAAGGGTGGATGGAGCTGCCATCCACTTCACGAAGTTGTTCCAAGTGTCACTA





AAACACTATGGTCCGTGGGCTGTGAGATTACAAAGGCGAAGGCAATAATACAAGAGAGTAGCATCTC





TCTTCTCGTGGAGACTACTGACATCATAAGTCCAAAAGTCAAAATTTCATCTAAGCATCGCCGCTTTGG





GAAATCAAATTGGGGTCTGTTCAAGAAAACCAAATCACTGCCCAACCTGACGGAGCTGGAATGACTG





ACCCCCAATCGAGACTACACCACCTCAAACTATAGGTGGGTGGTACCTCAGTGATTAATCTCGTAAGC





ACTGATCGTAGGCTACAACACACTAATATTATCCAGATTAGAGAGCTTAATTAGCTCTGTATTAATAAT





AACACTACTATTCCAATAACTGGAATCACCAGCTTGATTTATCTCCAAAATGATTCAAAGAAAACAAA





TCATATTAAGACTATCCTAAGCACGAACCCATATCGTCCTTCAAATCATGGGTACTATAATTCAATTTC





TGGTGGTCTCCTGTCTATTGGCAGGAGCAGGCAGTCTTGATCCAGCAGCCCTCATGCAAATCGGTGTC





ATTCCAACAAATGTCCGGCAACTTATGTATTATACTGAGGCCTCATCAGCATTCATTGTTGTGAAGTTA





ATGCCTACAATTGACTCGCCGATTAGTGGATGTAATATAACATCAATTTCAAGCTATAATGCAACAGT





GACAAAACTCCTACAGCCGATCGGTGAGAATTTGGAGACGATTAGGAACCAGTTGATTCCAACTCGGA





GGAGACGCCGGTTTGCAGGGGTGGTGATTGGATTAGCTGCATTAGGAGTAGCTACTGCCGCACAGGTC





ACTGCCGCAGTAGCACTAGTAAAGGCAAATGAAAATGCTGCGGCTATACTCAATCTCAAAAATGCAAT





CCAAAAAACAAATGCAGCAGTTGCAGATGTGGTCCAGGCCACACAATCACTAGGAACaGCAGTTCAAG





CAGTTCAAGATCACATAAACAGTGTGGTAAGTCCAGCAATTACAGCAGCCAATTGTAAAGCCCAAGAT





GCTATCATTGGCTCAATCCTCAATCTCTATTTGACCGAGTTGACAACTATCTTCCACAATCAAATTACA





AACCCTGCATTGAGTCCTATTACAATTCAAGCTTTAAGGATCCTACTAGGGAGTACCTTGCCGACTGTG





GTCGAAAAATCTTTCAATACCCAGATAAGTGCGGCTGAGCTTCTCTCATCAGGGTTATTGACAGGCCA





GATTGTGGGATTAGATTTGACCTATATGCAGATGGTCATAAAAATTGAGCTGCCAACTTTAACTGTAC





AACCTGCAACCCAGATCATAGATCTGGCCACCATTTCTGCATTCATTAACAATCAAGAAGTCATGGCC





CAATTACCAACACGTGTTATTGTGACTGGCAGCTTGATCCAAGCCTATCCCGCATCGCAATGCACTATT





ACACCCAACACTGTGTACTGTAGGTATAATGATGCCCAAGTACTCTCAGATGATACGATGGCTTGCCT





CCAAGGTAACTTGACAAGATGCACCTTCTCTCCAGTGGTTGGGAGCTTTCTCACTCGATTCGTGCTGTT





CGATGGAATAGTTTATGCAAATTGCAGGTCGATGTTGTGCAAGTGCATGCAGCCTGCTGCTGTGATCCT





ACAGCCGAGTTCATCCCCTGTAACTGTCATTGACATGTACAAATGTGTGAGTCTGCAGCTTGACAATCT





CAGATTCACCATCACTCAATTGGCCAATGTAACCTACAATAGCACCATCAAGCTTGAAACATCCCAGA





TCTTGCCTATTGATCCGTTGGATATATCCCAGAATCTAGCTGCGGTGAATAAGAGTCTAAGTGATGCAC





TACAACACTTAGCACAAAGTGACACATACCTTTCTGCAATCACATCAGCTACGACTACAAGTGTATTA





TCCATAATAGCAATCTGTCTTGGATCGTTAGGTTTAATATTAATAATCTTGCTCAGTGTAGTTGTGTGG





AAGTTATTGACCATTGTCGCTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAATTCAGCATTC





CACCACTCACGATCTGATCTCAGTGAGAAAAATCAACCTGCAACTCTTGGAACAAGATAAGACAGTCA





TCCATTAGTAATTTTTAAGAAAAAAACGATAGGACCGAAACTAGTATTGAAAGAACCGTCTCGGTCAA





TCTAGGTAATCGAGCTGcTACCGTCTCGGAAAGCTCAAATCgcgcgctaacgtacgCACCTGCTATAGGCTATC





CACTGCATCATCTCTTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCCGGTGCC





AACAACACAATCCACAATCTACAGTCGACGCGGCCGCCACCatgttcgtgttcctggtgctgctgccact





ggtcagcagccagtgcgtgaatttcactacccggacccagctgcctcctgcttatacaaacagcttcaccaggggag





tgtactaccccgataaggtgttccgcagctctgtgctgcacagcacccaggacttgtttcttcccttcttcagcaacgtg





acctggttccacgccatccacgtgtccggcaccaacggcaccaaaagattcgccaatcctgtgctgcctttcaacgatggc





gtgtactttgcctctacagagaagtctaacatcatcagaggctggatcttcggcacaaccctggattctaaaa





cccagagcctgctgatcgtgaacaatgccaccaatgtagtgatcaaggtttgtgagttccagttctgcaacgacccct





ttctgggcgtttactaccacaagaacaacaaaagctggatggaaagcgagttcagggtgtactctagcgcca





acaactgtaccttcgagtacgtgagccagccttttctgatggacctggagggcaagcagggcaacttcaaaaacct





gcgggagttcgtgtttaagaacatcgacggatacttcaagatttactccaagcacaccccaattaacttggttagaggact





gccccaaggcttcagcgccctggaacccctggtggacctgcctatcggcatcaacatcacaagattccaaaccctgcat





agaagctatctgacaccaggcgactctagctctggatggacagccggcgccgctgcttattacgtgggctacctgc





agcctagaaccttcctcctgaaatacaacgagaacggaaccatcaccgacgccgtggactgcgccctggatcctctgagcg





agacaaagtgcaccctgaagtccttcaccgtcgaaaagggcatctaccaaacaagcaacttcagagtgcagcctactg





agagcatcgtgcggtttccaaacatcaccaacctgtgtccttttggcgaggtgttcaacgccacccggttcgcttccgtgt





acgcctggaatagaaagcggatcagcaactgcgtggccgactacagcgtgctgtataatagcgcctcattttccgatctg





tgctttacttttaaatgttacggcgtgtctcctacaaagctgaacacaaatgtgtacgccgatagcttcgtgattag





aggcgacgaggtgcggcagatcgcccctggccagaccggcaacatcgctgactacaactacaagctgcctgacgacttc





accggctgtgtgatcgcatggaacagcaataacctggactctaaggtgggcggaaactacaattacctgtacagac





tgttcagaaagagcaacctgaagcccttcgagagagatatctccacagaaatctatcaggccggatctacaccttgtaatgg





cgtgaagggcttcaactgctacttccctctgcaatcctacggctttcagcccacatacggcgtgggctaccagccataccg





ggtcgtggtgctgagcttcgagctgctgcacgcccctgccacagtgtgcggccctaagaagagcaccaatctggta





aagaacaagtgcgtcaacttcaatttcaacggcctgaccgggaccggagtgctgaccgaaagcaacaagaaattcctg





ccgttccagcagttcggcagagatatcgccgacaccaccgatgccgtgcgggacccccagacacttgaaatcctggacatc





accccttgcagttttggcggcgtgtccgtgatcacacctggaacaaacaccagcaaccaggtggccgtgctgtaccaggg





cgtcaactgcaccgaggtccccgtggccatccacgccgatcagctgacacctacatggcgggtgtactctaccgg





cagcaacgtgttccaaaccagagccggctgcctgatcggcgctgagcacgtgaacaacagctacgagtgcgacattcct





atcggtgctggcatctgcgcctcttaccagacacagacaaacagccccagaagagcgagaagcgtggctagtcagagcatc





atcgcctacaccatgagcctgggcgtggagaacagcgtggcctactctaacaatagcatcgccatcccaaccaacttcaca





atctctgtgaccacagagatcctgcccgtgtccatgaccaagacatctgtggactgcacaatgtatatctgtgg





cgattctaccgagtgcagcaacctgctgctccagtacggcagcttttgtacccagctgaatagagccctgacaggcatcg





ccgtggagcaggataagaacacacaggaggtgttcgcccaggtgaagcaaatctacaagaccccccctatcaaggactt





tggcggcttcaatttttcccagatcctgcctgatccatccaagccttctaagcggagctttatcgaggacctg





ctgttcaacaaggtgaccctggccgatgccggcttcatcaagcagtatggcgattgcctgggcgacatcgcagccagg





gacctgatctgcgcccagaagtttaatggcctgaccgtgctgccacccctgctgacagatgagatgatcgcacagtac





acaagcgccctgctggccggcaccatcacatccggatggaccttcggcgcaggagccgccctccagatcccctt





tgccatgcagatggcctataggttcaacggcatcggcgtgacccagaatgtgctgtacgagaaccagaagctgat





cgccaatcagtttaactccgccatcggcaagatccaggacagcctgtcctctacagccagcgccctgggcaagctcca





ggatgtggtgaatcagaacgcccaggccctgaataccctggtgaagcagctgagcagcaacttcggcgccatctctagcgt





gctgaatgacatcctgagccggctggacaaggtggaggcagaggtgcagatcgaccggctgatcaccggccggctc





cagagcctccagacctatgtgacacagcagctgatcagggccgccgagatcagggccagcgccaatctggcagca





accaagatgtccgagtgcgtgctgggccagtctaagagagtggacttttgtggcaagggctatcacctgatgtccttccc





tcagtctgccccacacggcgtggtgtttctgcacgtgacctacgtgcccgcccaggagaagaacttcaccacagc





ccctgccatctgccacgatggcaaggcccactttccaagggagggcgtgttcgtgtccaacggcacccactggtttg





tgacacagcgcaatttctacgagccccagatcatcaccacagacaacaccttcgtgagcggcaactgtgacgtggtcat





cggcatcgtgaacaataccgtgtatgatccactccagcccgagctggacagctttaaggaggagctggataagtatttca





agaatcacacctcccctgacgtggatctgggcgacatcagcggcatcaatgcctccgtggtgaacatccagaag





gagatcgaccgcctgaacgaggtggctaagaatctgaacgagagcctgatcgacctccaggagctgggcaagtatgagcagta





catcaagtggccctggtacatctggctgggcttcatcgccggcctgatcgccatcgtgatggtgaccatcatgctgt





gctgtatgacatcctgctgttcttgcctgaagggctgctgtagctgtggctcctgctgtAAGTTATTGACCA





TTGTCGTTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAAATGAACGCGTGCTAGCCTCCTGC





CATACTTCCTACTCACATCATATCTATTTTAAAGAAAAAATAGGCCCGAACACTAATCGTGCCGGCAG





TGCCACTGCACACACAACACTACACATACAATACACTACAATGGTTGCAGAAGATGCCCCTGTTAGGG





GCACTTGCCGAGTATTATTTCGAACAACAACTTTAATTTTTCTATGCACACTATTAGCATTAAGCATCT





CTATCCTTTATGAGAGTTTAATAACCCAAAAGCAAATCATGAGCCAAGCAGGCTCAACTGGATCTAAT





TCTAGATTAGGAAGTATCACTGATCTTCTTAATAATATTCTCTCTGTCGCAAATCAGATTATATATAAC





TCTGCAGTCGCTCTACCTCTACAATTGGACACTCTTGAATCAACACTCCTTACAGCCATTAAGTCTCTT





CAAACAAGTGACAAGCTAGAACAGAACTGCTCGTGGGGTGCTGCACTGATTAATGATAATAGATACAT





TAATGGCATCAATCAGTTCTATTTCTCAATTGCTGAGGGTCGCAAGCTGACACTTGGCCCACTTCTTAA





TATACCTAGTTTCATTCCAACTGCCACGACACCAGAGGGCTGCACCAGGATCCCATCATTCTCGCTCAC





CAAGACACACTGGTGTTATACACACAATGTTATCCTGAATGGATGCCAGGATCATGTATCCTCAAATC





AATTTGTTTCCATGGGAATCATTGAACCCACTTCTGCCGGGTTTCCATCCTTTCGAACCCTAAAGACTC





TATATCTCAGCGATGGGGTCAATCGTAAGAGCTGCTCTATCAGTACAGTTCCGGGGGGTTGTATGATG





TACTGTTTCGTCTCTACTCAACCAGAGAGGGATGACTACTTTTCTACCGCTCCTCCAGAACAACGAATT





ATTATAATGTACTATAATGATACAATCGTGGAGCGCATAATTAATCCACCCGGGGTACTAGATGTATG





GGCAACATTGAACCCAGGAACAGGAAGCGGGGTATATTATTTAGGTTGGGTACTCTTTCCAATATATG





GCGGCGTGATTAAAGATACGAGTTTATGGAATAATCAAGCAAATAAATACTTTATCCCCCAGATGGTT





GCTGCTCTCTGCTCACAAAACCAGGCAACTCAAGTCCAAAATGCTAAGTCATCATACTATAGCAGCTG





GTTTGGCAATCGAATGATTCAGTCTGGGATCCTGGCATGTCCTCTTCAACAGGATCTAACCAATGAGTG





TTTAGTTCTGCCCTTTTCTAATGATCAGGTGCTTATGGGTGCTGAAGGGAGATTATACATGTATGGTGA





CTCGGTGTATTACTACCAAAGAAGCAATAGTTGGTGGCCTATGACCATGCTGTATAAGGTAACCATAA





CATTCACTAATGGTCAGCCATCTGCTATATCAGCTCAGAATGTGCCCACACAGCAGGTCCCTAGACCT





GGGACAGGAAGCTGCTCTGCAACAAATAGATGTCCCGGTTTTTGCTTGAAAGGAGTGTATGCTGATGC





CTGGTTACTGACCAACCCTTCGTCTACCAGTACATTTGGATCAGAAGCAACCTTCACTGGTTCTTATCT





CAACGCAGCAACTCAGCGTATCAATCCGACGATGTATATCGCGAACAACACACAGATCATAAGCTCAC





AGCAATTTGGATCAAGCGGTCAAGAAGCAGCATATGGCCACACAACTTGTTTTAGGGACACAGGCTCT





GTTATGGTATACTGTATCTATATTATTGAATTGTCCTCATCTCTCTTAGGACAATTTCAGATTGTCCCAT





TTATCCGTCAGGTGACACTATCCTAAAGGCAGAAGCCTCCAGGTCTGACCCAGCCAATCAAAGCATTA





TACCAGACCATGGAATGCATACCAAACATTATTGACACTAATGACACACAAAATTGGTTTTAAGAAAA





ACCAAGAGAACAATAGGCCAGAATGGCTGGGTCTCGGGAGATATTACTCCCTGAAGTCCATCTCAATT





CACCAATTGTAAAGCATAAGCTATACTATTACATTCTACTTGGAAACCTCCCAAATGAGATCGACATT





GACGATTTAGGTCCATTACATAATCAAAATTGGAATCAAATAGCACATGAAGAGTCTAACTTAGCCCA





ACGCTTGGTAAATGTAAGAAATTTTCTAATTACCCACATCCCTGATCTTAGAAAGGGCCATTGGCAAG





AGTATGTCAATGTAATACTGTGGCCGCGAATTCTTCCCTTGATCCCGGATTTTAAAATCAATGACCAAT





TGCCTCTACTCAAAAATTGGGACAAGTTAGTTAAAGAATCATGTTCAGTAATCAATGCGGGTACTTCC





CAGTGCATTCAGAATCTCAGCTATGGACTGACAGGTCGTGGGAACCTCTTTACACGATCACGTGAACT





CTCTGGTGACCGCAGGGATATTGATCTTAAGACGGTTGTGGCAGCATGGCATGACTCAGACTGGAAAA





GAATAAGTGATTTTTGGATTATGATCAAATTCCAGATGAGACAATTAATTGTTAGGCAAACAGATCAT





AATGATCCTGATTTAATCACGTATATCGAAAATAGAGAAGGCATAATCATCATAACCCCTGAACTGGT





AGCATTATTTAACACTGAGAATCATACACTAACATACATGACCTTTGAAATTGTACTGATGGTTTCAGA





TATGTACGAAGGTCGTCACAACATTTTATCACTATGCACAGTTAGCACTTACCTGAATCCTCTGAAGAA





AAGAATAACATATTTATTGAGCCTTGTAGATAACTTAGCTTTTCAGATAGGTGATGCTGTATATAACAT





AATTGCTTTGCTAGAATCCTTTGTATATGCACAGTTGCAAATGTCAGATCCCATCCCAGAACTCAGAGG





ACAATTCCATGCATTCGTATGTTCTGAGATTCTTGATGCACTAAGGGGAACTAATAGTTTCACCCAGGA





TGAATCAAGAACTGTGACAACCAATTTGATATCCCCATTCCAAGATCTGACCCCAGATCTTACGGCTG





AATTGCTCTGTATAATGAGGCTTTGGGGACACCCCATGCTCACCGCCAGTCAAGCTGCGGGAAAGGTA





CGCGAGTCCATGTGTGCTGGAAAAGTATTAGACTTTCCCACCATTATGAAAACACTAGCCTTTTTCCAT





ACTATTCTGATCAATGGATACAGGAGGAAGCATCATGGAGTATGGCCACCCTTAAACTTACCGGGTAA





TGCTTCAAAGGGTCTCACGGAACTTATGAATGACAATACTGAGATAAGCTATGAATTCACACTTAAGC





ATTGGAAGGAAATCTCTCTTATAAAATTCAAGAAATGTTTTGATGCAGACGCAGGTGAGGAACTCAGT





ATATTTATGAAAGATAAAGCAATTAGTGCCCCAAAACAAGATTGGATGAGTGTGTTTAGAAGAAGCCT





AATCAAACAGCGCCATCAGCATCATCAGGTCCCCCTACCAAATCCATTCAATCGACGGCTATTGCTAA





ACTTTCTCGGAGATGACAAATTCGACCCGAATGTGGAGCTACAGTATGTAACATCAGGTGAGTATCTA





CATGATGACACGTTTTGTGCATCATATTCACTAAAAGAGAAGGAAATTAAACCTGATGGTCGAATTTT





TGCAAAGTTGACTAAGAGAATGAGATCATGTCAAGTTATAGCAGAATCTCTTTTAGCGAACCATGCTG





GGAAGTTAATGAAAGAGAATGGTGTTGTGATGAATCAGCTATCATTAACAAAATCACTATTAACAATG





AGTCAGATTGGAATAATATCCGAGAAAGCTAGAAAATCGACTCGAGATAACATAAATCAACCTGGTTT





CCAGAATATCCAGAGAAATAAATCACATCACTCCAAGCAAGTCAATCAGCGAGATCCAAGTGATGAC





TTTGAATTGGCAGCATCTTTTTTAACTACTGATCTCAAAAAATATTGTTTACAATGGAGGTACCAGACA





ATTATCCCATTTGCTCAATCATTAAACAGAATGTATGGTTATCCTCATCTCTTTGAGTGGATTCACTTAC





GGCTAATGCGTAGTACACTTTACGTGGGGGATCCCTTCAACCCACCAGCAGATACCAGTCAATTTGAT





CTAGATAAAGTAATTAATGGAGATATCTTCATTGTATCACCCAGAGGTGGAATTGAAGGGCTATGTCA





AAAGGCTTGGACAATGATATCTATCTCTGTGATAATTCTATCTGCCACAGAGTCTGGCACACGAGTAA





TGAGTATGGTGCAGGGAGATAATCAAGCAATTGCTGTCACCACACGAGTACCAAGGAGCCTGCCGACT





CTTGAGAAAAAGACTATTGCTTTTAGATCTTGTAATCTATTCTTTGAGAGGTTAAAATGTAATAATTTT





GGATTAGGTCACCATTTGAAAGAACAAGAGACTATCATTAGTTCTCACTTCTTTGTTTATAGCAAGAGA





ATATTCTATCAGGGGAGGATTCTAACGCAAGCCTTAAAAAATGCTAGTAAGCTCTGCTTGACAGCTGA





TGTCCTAGGAGAATGTACCCAATCATCATGTTCTAATCTTGCAACTACTGTCATGAGGTTAACTGAGAA





TGGTGTTGAAAAAGATATCTGTTTCTACTTGAATATCTATATGACCATCAAACAGCTCTCCTATGATAT





CATCTTCCCTCAAGTGTCAATTCCTGGAGATCAGATCACATTAGAATACATAAATAATCCACACCTGGT





ATCACGATTGGCTCTTCTGCCATCCCAGCTAGGAGGTCTAAACTACCTGTCATGCAGTAGGCTGTTCAA





TCGAAACATAGGCGACCCGGTGGTTTCCGCAGTTGCAGATCTTAAGAGATTAATTAAATCAGGATGTA





TGGATTACTGGATCCTTTATAACTTATTAGGGAGAAAACCGGGAAACGGCTCATGGGCTACTTTAGCA





GCTGACCCGTACTCAATCAATATAGAGTATCAATACCCCCCAACTACAGCTCTTAAGAGGCACACCCA





ACAAGCTCTGATGGAACTCAGTACGAATCCAATGTTACGTGGCATATTCTCTGACAATGCACAGGCAG





AAGAAAATAATCTTGCTAGATTTCTCCTGGATAGGGAGGTGATCTTTCCGCGTGTAGCTCACATCATCA





TTGAGCAAACCAGTGTCGGGAGGAGAAAACAGATTCAAGGATATTTGGATTCAACTAGATCGATAAT





GAGTAAATCACTAGAAATTAAGCCCTTGTCCAATAGGAAGCTTAATGAAATACTGGATTACAACATCA





ATTACCTAGCTTACAATTTGGCATTACTCAAGAATGCTATTGAACCTCCGACTTATTTGAAAGCAATGA





CTCTTGAAACATGTAGCATCGACATTGCAAGGAGCCTCCGGAAGCTCTCCTGGGCCCCACTCTTGGGT





GGGAGAAATCTTGAAGGATTAGAGACGCCAGATCCCATTGAAATTACTGCAGGAGCATTAATTGTTGG





ATCGGGCTACTGTGAACAGTGTGCTGCAGGAGACAATCGATTCACATGGTTTTTCTTGCCATCTGGTAT





CGAGATAGGAGGGGATCCCCGTGATAATCCTCCTATCCGTGTACCGTACATTGGCTCCAGGACTGATG





AGAGGAGGGTAGCCTCAATGGCATACATCAGGGGTGCCTCGAGTAGCCTAAAAGCAGTTCTTAGACTG





GCGGGAGTGTACATCTGGGCATTCGGAGATACTCTGGAGAATTGGATAGATGCACTGGATTTGTCTCA





CACTAGAGTTAACATCACACTTGAACAGCTGCAATCCCTCACCCCACTTCCAACCTCTGCCAATCTAAC





CCATCGGTTGGATGATGGCACAACTACCCTAAAGTTTACTCCTGCGAGCTCTTACACCTTTTCAAGTTT





CACTCATATATCAAATGATGAGCAATACCTGACAATTAATGACAAAACTGCAGATTCAAATATAATCT





ACCAACAGTTAATGATCACTGGACTCGGAATTTTAGAAACATGGAATAATCCCCCAATCAATAGAACA





TTCGAAGAATCTACCCTACATTTGCACACTGGTGCATCATGTTGTGTCCGACCTGTGGACTCCTGCATC





ATCTCAGAAGCATTAACAGTCAAGCCACATATTACAGTACCGTACAGCAATAAATTTGTATTTGATGA





AGACCCGCTATCTGAATATGAGACTGCAAAACTGGAATCGTTATCATTTCAAGCCCAATTAGGCAACA





TTGATGCTGTAGATATGACAGGTAAATTAACATTATTGTCCCAATTCACTGCAAGGCAGATTATTAATG





CAATCACTGGACTCGATGAGTCTGTCTCTCTTACTAATGATGCCATTGTTGCATCAGACTATGTCTCCA





ATTGGATTAGTGAATGCATGTATACCAAATTAGATGAATTATTTATGTATTGTGGGTGGGAACTACTAT





TGGAACTATCCTATCAAATGTATTATCTGAGGGTAGTTGGGTGGAGTAATATAGTGGATTATTCTTACA





TGATCTTGAGAAGAATCCCGGGTGCAGCATTAAACAATCTGGCATCTACATTAAGTCATCCAAAACTT





TTCCGACGAGCTATCAACCTAGATATAGTTGCCCCCTTAAATGCTCCTCATTTTGCATCTCTGGACTAC





ATCAAGATGAGTGTGGATGCAATACTCTGGGGCTGTAAAAGAGTCATCAATGTGCTCTCCAATGGAGG





GGACTTAGAATTAGTTGTGACATCTGAAGATAGCCTTATTCTCAGTGACCGATCCATGAATCTCATTGC





AAGGAAATTAACTTTATTATCACTGATTCACCATAATGGTTTGGAACTACCAAAGATTAAGGGGTTCTC





TCCTGATGAGAAGTGTTTCGCTTTGACAGAATTTTTGAGGAAAGTGGTGAACTCAGGGTTGAGTTCAA





TAGAGAACCTATCAAATTTTATGTACAATGTGGAGAACCCACGGCTTGCAGCATTCGCCAGCAACAAT





TACTACCTGACCAGAAAATTATTGAATTCAATACGAGATACTGAGTCGGGTCAAGTAGCAGTCACCTC





ATATTATGAATCATTAGAATATATTGATAGTCTTAAGCTAACCCCACATGTGCCTGGTACCTCATGCAT





TGAGGATGATAGTCTATGTACAAATGATTACATAATCTGGATCATAGAGTCTAATGCAAACTTGGAGA





AGTATCCAATTCCAAATAGCCCTGAGGATGATTCCAATTTCCATAACTTTAAGTTGAATGCTCCATCGC





ACCATACCTTACGCCCATTAGGGTTGTCATCAACTGCTTGGTATAAGGGTATAAGCTGTTGCAGGTACC





TTGAGCGATTAAAGCTACCACAAGGTGATCATTTATATATTGCAGAAGGTAGTGGTGCCAGTATGACA





ATCATAGAATACCTATTCCCAGGAAGAAAGATATATTACAATTCTTTATTTAGTAGTGGTGACAATCCC





CCACAAAGAAATTATGCACCAATGCCTACTCAGTTCATTGAGAGTGTCCCATACAAGCTCTGGCAAGC





ACACACAGATCAATATCCCGAGATTTTTGAGGACTTCATCCCTCTATGGAACGGAAATGCCGCCATGA





CTGACATAGGAATGACAGCTTGTGTAGAATTCATCATCAATCGAGTCGGCCCAAGGACTTGCAGTTTA





GTACATGTAGATTTGGAATCAAGTGCAAGCTTAAATCAACAATGCCTGTCAAAGCCGATAATTAATGC





TATCATCACTGCTACAACTGTTTTGTGCCCTCATGGGGTGCTTATTCTGAAATATAGTTGGTTGCCATTT





ACTAGATTTAGTACTTTGATCACTTTCTTATGGTGCTACTTTGAGAGAATCACTGTTCTTAGGAGCACA





TATTCTGGTCCAGCTAATCATGAGGTTTATTTAATTTGTATCCTTGCCAACAACTTTGCATTCCAGACTG





TCTCGCAGGCAACAGGAATGGCGATGACTTTAACCGATCAAGGGTTTACTTTGATATCACCTGAAAGA





ATAAATCAGTATTGGGATGGTCACTTGAAGCAAGAACGTATCGTAGCAGAAGCAATTGATAAGGTGGT





TCTAGGAGAAGATGCTCTATTCAATTCGAGTGATAATGAATTAATTCTCAAATGTGGAGGGACACCAA





ATGCACGGAATCTTATCGATATCGAGCCAGTCGCAACTTTCATAGAATTTGAACAACTGATCTGCACA





ATGTTGACAACCCACTTGAAGGAAATAATTGATATAACAAGGTCTGGAACCCAGGATTATGAAAGTTT





ATTACTCACTCCTTACAATTTAGGTCTTCTTGGTAAAATCAGTACGATAGTGAGATTATTAACAGAAAG





GATTCTAAATCATACTATCAGGAATTGGTTGATCCTCCCACCTTCGCTCCGGATGATCGTGAAGCAGGA





CTTGGAATTCGGCATATTCAGGATTACTTCCATCCTCAATTCTGATCGGTTCCTGAAGCTTTCTCCAAAT





AGGAAATACTTGATTACACAATTAACTGCAGGCTACATTAGGAAATTGATTGAGGGGGATTGTAATAT





CGATCTAACCAGACCTATCCAAAAACAAATCTGGAAAGCATTAGGTTGTGTAGTCTATTGTCACGATC





CAGTAGATCAAAGGGAATCAACAGAGTTTATTGATATAAATATTAATGAAGAAATAGACCGCGGGAT





CGATGGCGAGGAAATCTAAATATATCAAGAATCAGAATTAGTTTAAGAAAAAAGAAGAGGATTAATC





TTGGTTTTCCCCTTGGT.






11. CVL59


The nucleic acid sequence for CVL58 is:










(SEQ ID NO: 71)



ACCAGGGGGAAAACGAAGTGGTGACTCAAATCATCGAAGACCCTCGAGATTACATAGGTCCGGAACC






TATGGCCTTCGTGACCGACCTCGAGTCAGAGTAGTTCAATAAGGACCTATCAAGTTTGGGCAATTTTTC





GTCCCCGACACAAAAATGTCATCCGTGCTTAAAGCATATGAGCGATTCACACTCACTCAAGAACTGCA





AGATCAGAGTGAGGAAGGTACAATCCCACCTACAACACTAAAACCGGTAATCAGGGTATTTATACTAA





CCTCTAATAACCCAGAGCTAAGATCCCGGCTTCTTCTATTCTGCCTACGGATTGTTCTCAGTAATGGTG





CAAGGGATTCCCATCGCTTTGGAGCATTACTTACAATGTTTTCGCTACCATCAGCCACAATGCTCAATC





ATGTCAAATTAGCTGACCAGTCACCAGAAGCTGATATCGAAAGGGTAGAGATCGATGGCTTTGAGGA





GGGATCATTCCGCTTAATCCCCAATGCTCGTTCAGGTATGAGCCGTGGAGAGATCAATGCCTATGCTG





CACTTGCAGAAGATCTACCTGACACACTAAACCATGCAACACCTTTTGTTGATTCCGAAGTCGAGGGA





ACTGCATGGGATGAGATTGAGACTTTCTTAGATATGTGTTACAGTGTCCTAATGCAGGCATGGATAGT





GACTTGCAAGTGCATGACTGCGCCAGACCAACCTGCTGCTTCTATTGAGAAACGCCTGCAAAAATATC





GTCAGCAAGGCAGGATCAACCCGAGATATCTCCTGCAACCGGAGGCTCGAAGAATAATCCAGAATGT





AATCCGAAAGGGAATGGTGGTCAGACATTTCCTCACCTTTGAACTGCAGCTTGCCCGAGCACAAAGCC





TTGTATCAAATAGGTATTATGCTATGGTAGGGGATGTTGGAAAGTATATAGAGAATTGTGGAATGGGA





GGCTTCTTTTTGACACTAAAATATGCATTAGGAACCAGATGGCCCACACTTGCTTTAGCTGCATTTTCA





GGAGAGCTAACAAAGCTAAAGTCCCTCATGGCATTATACCAGACCCTTGGTGAGCAGGCCCGATATTT





GGCCCTATTGGAGTCACCACATTTGATGGATTTTGCTGCAGCAAACTACCCACTGCTATATAGCTATGC





TATGGGAATAGGCTATGTGTTAGATGTCAACATGAGGAACTACGCTTTCTCCAGATCATACATGAATA





AGACATATTTCCAATTGGGAATGGAAACTGCAAGAAAACAACAGGGTGCAGTTGACATGAGGATGGC





AGAAGATCTCGGTCTAACTCAAGCCGAACGCACCGAGATGGCAAATACACTTGCCAAATTGACCACA





GCAAATCGAGGGGCAGACACCAGGGGAGGAGTCAACCCGTTCTCATCTATCACTGGGACAACTCAGG





TGCCCGCTGCAGCAACAGGTGACACATTCGAGAGTTACATGGCAGCGGATCGACTGAGGCAGAGATA





TGCTGATGCAGGCACCCACGATGATGAGATGCCACCATTGGAAGAGGAGGAAGAGGACGACACATCT





GCAGGTCCACGCACTGGACTAACTCTTGAACAAGTGGCCTTGGACATCCAGAACGCAGCAGTTGGAGC





TCCCATCCATACAGATGACCTGAATGCCGCACTGGGTGATCTTGACATCTAGACAATTCAGATCCCAA





TCTTAAATCGACACACCTAATTGACCAGTTAGATGGAACTACAGTGGATTCCATAAGGTTCCTGCCTAC





CATCGGCTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCCGATGCCAATAACA





CAATCCACAATCTACAATGGATCCCACTGATCTGAGCTTCTCCCCAGATGAGATCAATAAGCTCATAG





AGACAGGCCTGAATACTGTGGAGTATTTTACTTCCCAACAAGTCACAGGAACATCCTCTCTTGGAAAG





AATACAATACCACCAGGGGTCACAGGACTACTAACCAATGCTGCAGAGGCAAAGATCCAAGAGTCAA





CCAACCATCAGAAGGGTTCAGTTGGTGGGGGCGCAAAACCAAAGAAACCGCGACCAAAAATTGCCAT





TGTGCCAGCAGATGACAAAACGGTGCCCGGAAAGCCGATCCCAAACCCTCTATTAGGTCTGGACTCCA





CCCCGAGCACCCAAACTGTGCTTGATCTAAGTGGGAAAACATTACCATCAGGATCCTATAAGGGGGTT





AAACTTGCGAAATTTGGAAAAGAAAATCTGATGACACGGTTCATCGAGGAACCCAGAGAGAATCCTA





TCGCAACCAATTTCCCCATCGATTTTAAGAGGGGCAGGGATACCGGCGGGTTCCATAGAAGGGAGTAC





TCAATCGGATGGGTGGGAGATGAAGTCAAGGTCACTGAGTGGTGCAATCCATCCTGTTCTCCAATCAC





CGCTGCAGCAAGGCGATTTGAATGCACTTGTCACCAGTGTCCAGTCACTTGCTCTGAATGTGAACGAG





ATACTTAATACAGTGAGAAATTTGGACTCTCGGATGAATCAACTGGAGACAAAAGTAGATCGCATTCT





CTCATCTCAGTCTCTAATCCAGACCATCAAGAATGACATAGTTGGACTTAAAGCAGGGATGGCTACTT





TAGAAGGAATGATTACAACTGTGAAAATCATGGACCCGGGAGTTCCCAGTAATGTTACTGTGGAAGAT





GTACGCAAGAAACTAAGTAACCATGCTGTTGTTGTGCCAGAATCATTCAATGATgccTTCTTGACTCAAT





CTGAAGATGTAATTTCACTTGATGAGTTGGCTCGACCAACTGCAACAAGTGTTAAGAAGATTGTCAGG





AAGGTTCCTCCTCAGAAGGATCTGACTGGATTGAAGATCACACTAGAGCAATTGGCAAAGGATTGCAT





CAGCAAACCGAAGATGAGGGAAGAGTATCTCCTCAAAATCAACCAGGCTTCCAGTGAGGCTCAGCTA





ATTGACCTCAAGAAAGCAATCATCCGCAGTGCAATTTGATCAAGAAACACCCAATTACACTACACTGG





TATGACACTGTACTAACCCTGAGGGTTTTAGAAAAAACGATTAACGATAAATAAGCCCGAACACTACA





CACCACCCGAGGCAGCCATGCCATCCATCAGCATCCCCGCAGACCCCACCAATCCACGTCAATCAATA





AAAGCGTTCCCAATTGTGATCAACCGTGATGGGGGTGAGAAAGGTCGCTTGGTTAAACAACTACGCAC





AACCTACTTGAATGACCTAGATACTCATGAGCCACTGGTGACATTCGTAAATACTTATGGATTCATCTA





CGAACAGGATCGGGGAAATACCATTGTCGGAGAGGATCAACATGGGAAGAAAAGAGAGGCTGTGACT





GCTGCAATGGTTACCCTTGGATGTGGGCCTAATCTACCATCATTAGGGAATGTCCTGGGACAACTGAG





TGAATTCCAGGTCATTGTTAGGAAGACATCCAGCAAAGCGGAAGAGATGGTCTTTGAAATTGTTAAGT





ATCCGAGAATATTTCGGGGTCATACATTAATCCAGAAAGGACTAGTCTGTGTCTCCGCAGAAAAATTT





GTTAAGTCACCAGGGAAAGTACAATCTGGAATGGACTATCTCTTCATTCCGACATTTCTGTCAGTGACT





TACTGTCCAGCTGCAATCAAATTTCAGGTACCTGGCCCCATGTTGAAAATGAGATCAAGATACACTCA





GAGCTTACAACTTGAACTAATGATAAGAATCCTGTGTAAGCCCGATTCGCCACTTATGAAGGTCCATA





TCCCTGACAAGGAAGGAAGAGGATGTCTTGTATCAGTATGGTTGCATGTATGCAATATCTTCAAATCA





GGAAACAAGAATGGCAGTGAGTGGCAGGAATACTGGATGAGAAAGTGTGCTAACATGCAACTTGAAG





TGTCGATTGCAGATATGTGGGGACCAACTATCATAATTCATGCCAGAGGTCACATTCCCAAAAGTGCT





AAGTTGTTTTTTGGAAAGGGTGGATGGAGCTGCCATCCACTTCACGAAGTTGTTCCAAGTGTCACTAA





AACACTATGGTCCGTGGGCTGTGAGATTACAAAGGCGAAGGCAATAATACAAGAGAGTAGCATCTCT





CTTCTCGTGGAGACTACTGACATCATAAGTCCAAAAGTCAAAATTTCATCTAAGCATCGCCGCTTTGGG





AAATCAAATTGGGGTCTGTTCAAGAAAACCAAATCACTGCCCAACCTGACGGAGCTGGAATGACTGAC





CCCCAATCGAGACTACACCACCTCAAACTATAGGTGGGTGGTACCTCAGTGATTAATCTCGTAAGCAC





TGATCGTAGGCTACAACACACTAATATTATCCAGATTAGAGAGCTTAATTAGCTCTGTATTAATAATAA





CACTACTATTCCAATAACTGGAATCACCAGCTTGATTTATCTCCAAAATGATTCAAAGAAAACAAATC





ATATTAAGACTATCCTAAGCACGAACCCATATCGTCCTTCAAATCATGGGTACTATAATTCAATTTCTG





GTGGTCTCCTGTCTATTGGCAGGAGCAGGCAGTCTTGATCCAGCAGCCCTCATGCAAATCGGTGTCATT





CCAACAAATGTCCGGCAACTTATGTATTATACTGAGGCCTCATCAGCATTCATTGTTGTGAAGTTAATG





CCTACAATTGACTCGCCGATTAGTGGATGTAATATAACATCAATTTCAAGCTATAATGCAACAGTGAC





AAAACTCCTACAGCCGATCGGTGAGAATTTGGAGACGATTAGGAACCAGTTGATTCCAACTCGGAGGA





GACGCCGGTTTGCAGGGGTGGTGATTGGATTAGCTGCATTAGGAGTAGCTACTGCCGCACAGGTCACT





GCCGCAGTAGCACTAGTAAAGGCAAATGAAAATGCTGCGGCTATACTCAATCTCAAAAATGCAATCCA





AAAAACAAATGCAGCAGTTGCAGATGTGGTCCAGGCCACACAATCACTAGGAACaGCAGTTCAAGCA





GTTCAAGATCACATAAACAGTGTGGTAAGTCCAGCAATTACAGCAGCCAATTGTAAAGCCCAAGATGC





TATCATTGGCTCAATCCTCAATCTCTATTTGACCGAGTTGACAACTATCTTCCACAATCAAATTACAAA





CCCTGCATTGAGTCCTATTACAATTCAAGCTTTAAGGATCCTACTAGGGAGTACCTTGCCGACTGTGGT





CGAAAAATCTTTCAATACCCAGATAAGTGCGGCTGAGCTTCTCTCATCAGGGTTATTGACAGGCCAGA





TTGTGGGATTAGATTTGACCTATATGCAGATGGTCATAAAAATTGAGCTGCCAACTTTAACTGTACAAC





CTGCAACCCAGATCATAGATCTGGCCACCATTTCTGCATTCATTAACAATCAAGAAGTCATGGCCCAA





TTACCAACACGTGTTATTGTGACTGGCAGCTTGATCCAAGCCTATCCCGCATCGCAATGCACTATTACA





CCCAACACTGTGTACTGTAGGTATAATGATGCCCAAGTACTCTCAGATGATACGATGGCTTGCCTCCA





AGGTAACTTGACAAGATGCACCTTCTCTCCAGTGGTTGGGAGCTTTCTCACTCGATTCGTGCTGTTCGA





TGGAATAGTTTATGCAAATTGCAGGTCGATGTTGTGCAAGTGCATGCAGCCTGCTGCTGTGATCCTACA





GCCGAGTTCATCCCCTGTAACTGTCATTGACATGTACAAATGTGTGAGTCTGCAGCTTGACAATCTCAG





ATTCACCATCACTCAATTGGCCAATGTAACCTACAATAGCACCATCAAGCTTGAAACATCCCAGATCTT





GCCTATTGATCCGTTGGATATATCCCAGAATCTAGCTGCGGTGAATAAGAGTCTAAGTGATGCACTAC





AACACTTAGCACAAAGTGACACATACCTTTCTGCAATCACATCAGCTACGACTACAAGTGTATTATCC





ATAATAGCAATCTGTCTTGGATCGTTAGGTTTAATATTAATAATCTTGCTCAGTGTAGTTGTGTGGAAG





TTATTGACCATTGTCGCTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAATTCAGCATTCCAC





CACTCACGATCTGATCTCAGTGAGAAAAATCAACCTGCAACTCTTGGAACAAGATAAGACAGTCATCC





ATTAGTAATTTTTAAGAAAAAAACGATAGGACCGAAACTAGTATTGAAAGAACCGTCTCGGTCAATCT





AGGTAATCGAGCTGcTACCGTCTCGGAAAGCTCAAATCgcgcgctaacgtacgCACCTGCTATAGGCTATCCAC





TGCATCATCTCTTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCCGGTGCCAAC





AACACAATCCACAATCTACAGTCGACGCGGCCGCCACCatgttcgtgttcctggtgctgctgccactggtc





agcagccagtgcgtgaatttcactacccggacccagctgcctcctgcttatacaaacagcttcaccaggggagtg





tactaccccgataaggtgttccgcagctctgtgctgcacagcacccaggacttgtttcttcccttctt





cagcaacgtgacctggttccacgccatccacgtgtccggcaccaacggcaccaaaagattcgccaatcctgtg





ctgcctttcaacgatggcgtgtactttgcctctacagagaagtctaacatcatcagaggctggatcttcggc





acaaccctggattctaaaacccagagcctgctgatcgtgaacaatgccaccaatgtagtgatca





aggtttgtgagttccagttctgcaacgacccctttctgggcgtttactaccacaagaacaacaaaagctg





gatggaaagcgagttcagggtgtactctagcgccaacaactgtaccttcgagtacgtgagccagcctttt





ctgatggacctggagggcaagcagggcaacttcaaaaacctgcgggagttcgtgtttaagaacatcgacggata





cttcaagatttactccaagcacaccccaattaacttggttagaggactgccccaaggcttcagcgccctggaa





cccctggtggacctgcctatcggcatcaacatcacaagattccaaaccctgcatagaagctatctgac





accaggcgactctagctctggatggacagccggcgccgctgcttattacgtgggctacctgcagcctagaa





ccttcctcctgaaatacaacgagaacggaaccatcaccgacgccgtggactgcgccctggatcctctga





gcgagacaaagtgcaccctgaagtccttcaccgtcgaaaagggcatctaccaaacaagcaacttcagagtgc





agcctactgagagcatcgtgcggtttccaaacatcaccaacctgtgtccttttggcgaggtgttcaacgc





cacccggttcgcttccgtgtacgcctggaatagaaagcggatcagcaactgcgtggccgactacagcgtgctg





tataatagcgcctcattttctacttttaaatgttacggcgtgtctcctacaaagctgaacgatctgtgcttcac





aaatgtgtacgccgatagcttcgtgattagaggcgacgaggtgcggcagatcgcccctggccagaccggcaa





catcgctgactacaactacaagctgcctgacgacttcaccggctgtgtgatcgcatggaacagcaataacct





ggactctaaggtgggcggaaactacaattacctgtacagactgttcagaaagagcaacctgaagcccttcgagagag





atatctccacagaaatctatcaggccggatctacaccttgtaatggcgtgaagggcttcaactgctacttccc





tctgcaatcctacggctttcagcccacatacggcgtgggctaccagccataccgggtcgtggtgctgagcttc





gagctgctgcacgcccctgccacagtgtgcggccctaagaagagcaccaatctggtaaagaacaagtgcgtcaact





tcaatttcaacggcctgaccgggaccggagtgctgaccgaaagcaacaagaaattcctgccgttccagcagttcg





gcagagatatcgccgacaccaccgatgccgtgcgggacccccagacacttgaaatcctggacatcaccccttgcagtttt





ggcggcgtgtccgtgatcacacctggaacaaacaccagcaaccaggtggccgtgctgtaccagggcgtcaactgca





ccgaggtccccgtggccatccacgccgatcagctgacacctacatggcgggtgtactctaccggcagcaacgtgt





tccaaaccagagccggctgcctgatcggcgctgagcacgtgaacaacagctacgagtgcgacattcctatcgg





tgctggcatctgcgcctcttaccagacacagacaaacagccccagaagagcgagaagcgtggctagtcagagcatca





tcgcctacaccatgagcctgggcgtggagaacagcgtggcctactctaacaatagcatcgccatcccaacca





acttcacaatctctgtgaccacagagatcctgcccgtgtccatgaccaagacatctgtggactgcacaatgtatat





ctgtggcgattctaccgagtgcagcaacctgctgctccagtacggcagcttttgtacccagctgaatagagccctgac





aggcatcgccgtggagcaggataagaacacacaggaggtgttcgcccaggtgaagcaaatctacaagaccccccctatca





aggactttggcggcttcaatttttcccagatcctgcctgatccatccaagccttctaagcggagctttatcgaggacctg





ctgttcaacaaggtgaccctggccgatgccggcttcatcaagcagtatggcgattgcctgggcgacatcgcagccaggg





acctgatctgcgcccagaagtttaatggcctgaccgtgctgccacccctgctgacagatgagatgatcgcacagtacac





aagcgccctgctggccggcaccatcacatccggatggaccttcggcgcaggagccgccctccagatcccctttgccat





gcagatggcctataggttcaacggcatcggcgtgacccagaatgtgctgtacgagaaccagaagctgatcgccaat





cagtttaactccgccatcggcaagatccaggacagcctgtcctctacagccagcgccctgggcaagctccaggatgtgg





tgaatcagaacgcccaggccctgaataccctggtgaagcagctgagcagcaacttcggcgccatctctagcgtgctgaat





gacatcctgagccggctggacaaggtggaggcagaggtgcagatcgaccggctgatcaccggccggctccagag





cctccagacctatgtgacacagcagctgatcagggccgccgagatcagggccagcgccaatctggcagcaaccaaga





tgtccgagtgcgtgctgggccagtctaagagagtggacttttgtggcaagggctatcacctgatgtccttccctcagtc





tgccccacacggcgtggtgtttctgcacgtgacctacgtgcccgcccaggagaagaacttcaccacagcccctgcc





atctgccacgatggcaaggcccactttccaagggagggcgtgttcgtgtccaacggcacccactggtttgtgacac





agcgcaatttctacgagccccagatcatcaccacagacaacaccttcgtgagcggcaactgtgacgtggtcat





cggcatcgtgaacaataccgtgtatgatccactccagcccgagctggacagctttaaggaggagctggataagta





tttcaagaatcacacctcccctgacgtggatctgggcgacatcagcggcatcaatgcctccgtggtgaacatccag





aaggagatcgaccgcctgaacgaggtggctaagaatctgaacgagagcctgatcgacctccaggagctgggcaagtatga





gcagtacatcaagtggccctggtacatctggctgggcttcatcgccggcctgatcgccatcgtgatggtgaccatcatgc





tgtgctgtatgacatcctgctgttcttgcctgaagggctgctgtagctgtggctcctgctgtAAGTTATTGACCATTGTC





GTTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAAATGAACGCGTGCTAGCCTCCTGCCATAC





TTCCTACTCACATCATATCTATTTTAAAGAAAAAATAGGCCCGAACACTAATCGTGCCGGCAGTGCCA





CTGCACACACAACACTACACATACAATACACTACAATGGTTGCAGAAGATGCCCCTGTTAGGGGCACT





TGCCGAGTATTATTTCGAACAACAACTTTAATTTTTCTATGCACACTATTAGCATTAAGCATCTCTATCC





TTTATGAGAGTTTAATAACCCAAAAGCAAATCATGAGCCAAGCAGGCTCAACTGGATCTAATTCTAGA





TTAGGAAGTATCACTGATCTTCTTAATAATATTCTCTCTGTCGCAAATCAGATTATATATAACTCTGCA





GTCGCTCTACCTCTACAATTGGACACTCTTGAATCAACACTCCTTACAGCCATTAAGTCTCTTCAAACA





AGTGACAAGCTAGAACAGAACTGCTCGTGGGGTGCTGCACTGATTAATGATAATAGATACATTAATGG





CATCAATCAGTTCTATTTCTCAATTGCTGAGGGTCGCAAGCTGACACTTGGCCCACTTCTTAATATACC





TAGTTTCATTCCAACTGCCACGACACCAGAGGGCTGCACCAGGATCCCATCATTCTCGCTCACCAAGA





CACACTGGTGTTATACACACAATGTTATCCTGAATGGATGCCAGGATCATGTATCCTCAAATCAATTTG





TTTCCATGGGAATCATTGAACCCACTTCTGCCGGGTTTCCATCCTTTCGAACCCTAAAGACTCTATATC





TCAGCGATGGGGTCAATCGTAAGAGCTGCTCTATCAGTACAGTTCCGGGGGGTTGTATGATGTACTGT





TTCGTCTCTACTCAACCAGAGAGGGATGACTACTTTTCTACCGCTCCTCCAGAACAACGAATTATTATA





ATGTACTATAATGATACAATCGTGGAGCGCATAATTAATCCACCCGGGGTACTAGATGTATGGGCAAC





ATTGAACCCAGGAACAGGAAGCGGGGTATATTATTTAGGTTGGGTACTCTTTCCAATATATGGCGGCG





TGATTAAAGATACGAGTTTATGGAATAATCAAGCAAATAAATACTTTATCCCCCAGATGGTTGCTGCT





CTCTGCTCACAAAACCAGGCAACTCAAGTCCAAAATGCTAAGTCATCATACTATAGCAGCTGGTTTGG





CAATCGAATGATTCAGTCTGGGATCCTGGCATGTCCTCTTCAACAGGATCTAACCAATGAGTGTTTAGT





TCTGCCCTTTTCTAATGATCAGGTGCTTATGGGTGCTGAAGGGAGATTATACATGTATGGTGACTCGGT





GTATTACTACCAAAGAAGCAATAGTTGGTGGCCTATGACCATGCTGTATAAGGTAACCATAACATTCA





CTAATGGTCAGCCATCTGCTATATCAGCTCAGAATGTGCCCACACAGCAGGTCCCTAGACCTGGGACA





GGAAGCTGCTCTGCAACAAATAGATGTCCCGGTTTTTGCTTGAAAGGAGTGTATGCTGATGCCTGGTT





ACTGACCAACCCTTCGTCTACCAGTACATTTGGATCAGAAGCAACCTTCACTGGTTCTTATCTCAACGC





AGCAACTCAGCGTATCAATCCGACGATGTATATCGCGAACAACACACAGATCATAAGCTCACAGCAAT





TTGGATCAAGCGGTCAAGAAGCAGCATATGGCCACACAACTTGTTTTAGGGACACAGGCTCTGTTATG





GTATACTGTATCTATATTATTGAATTGTCCTCATCTCTCTTAGGACAATTTCAGATTGTCCCATTTATCC





GTCAGGTGACACTATCCTAAAGGCAGAAGCCTCCAGGTCTGACCCAGCCAATCAAAGCATTATACCAG





ACCATGGAATGCATACCAAACATTATTGACACTAATGACACACAAAATTGGTTTTAAGAAAAACCAAG





AGAACAATAGGCCAGAATGGCTGGGTCTCGGGAGATATTACTCCCTGAAGTCCATCTCAATTCACCAA





TTGTAAAGCATAAGCTATACTATTACATTCTACTTGGAAACCTCCCAAATGAGATCGACATTGACGATT





TAGGTCCATTACATAATCAAAATTGGAATCAAATAGCACATGAAGAGTCTAACTTAGCCCAACGCTTG





GTAAATGTAAGAAATTTTCTAATTACCCACATCCCTGATCTTAGAAAGGGCCATTGGCAAGAGTATGT





CAATGTAATACTGTGGCCGCGAATTCTTCCCTTGATCCCGGATTTTAAAATCAATGACCAATTGCCTCT





ACTCAAAAATTGGGACAAGTTAGTTAAAGAATCATGTTCAGTAATCAATGCGGGTACTTCCCAGTGCA





TTCAGAATCTCAGCTATGGACTGACAGGTCGTGGGAACCTCTTTACACGATCACGTGAACTCTCTGGTG





ACCGCAGGGATATTGATCTTAAGACGGTTGTGGCAGCATGGCATGACTCAGACTGGAAAAGAATAAG





TGATTTTTGGATTATGATCAAATTCCAGATGAGACAATTAATTGTTAGGCAAACAGATCATAATGATCC





TGATTTAATCACGTATATCGAAAATAGAGAAGGCATAATCATCATAACCCCTGAACTGGTAGCATTAT





TTAACACTGAGAATCATACACTAACATACATGACCTTTGAAATTGTACTGATGGTTTCAGATATGTACG





AAGGTCGTCACAACATTTTATCACTATGCACAGTTAGCACTTACCTGAATCCTCTGAAGAAAAGAATA





ACATATTTATTGAGCCTTGTAGATAACTTAGCTTTTCAGATAGGTGATGCTGTATATAACATAATTGCT





TTGCTAGAATCCTTTGTATATGCACAGTTGCAAATGTCAGATCCCATCCCAGAACTCAGAGGACAATTC





CATGCATTCGTATGTTCTGAGATTCTTGATGCACTAAGGGGAACTAATAGTTTCACCCAGGATGAATCA





AGAACTGTGACAACCAATTTGATATCCCCATTCCAAGATCTGACCCCAGATCTTACGGCTGAATTGCTC





TGTATAATGAGGCTTTGGGGACACCCCATGCTCACCGCCAGTCAAGCTGCGGGAAAGGTACGCGAGTC





CATGTGTGCTGGAAAAGTATTAGACTTTCCCACCATTATGAAAACACTAGCCTTTTTCCATACTATTCT





GATCAATGGATACAGGAGGAAGCATCATGGAGTATGGCCACCCTTAAACTTACCGGGTAATGCTTCAA





AGGGTCTCACGGAACTTATGAATGACAATACTGAGATAAGCTATGAATTCACACTTAAGCATTGGAAG





GAAATCTCTCTTATAAAATTCAAGAAATGTTTTGATGCAGACGCAGGTGAGGAACTCAGTATATTTAT





GAAAGATAAAGCAATTAGTGCCCCAAAACAAGATTGGATGAGTGTGTTTAGAAGAAGCCTAATCAAA





CAGCGCCATCAGCATCATCAGGTCCCCCTACCAAATCCATTCAATCGACGGCTATTGCTAAACTTTCTC





GGAGATGACAAATTCGACCCGAATGTGGAGCTACAGTATGTAACATCAGGTGAGTATCTACATGATGA





CACGTTTTGTGCATCATATTCACTAAAAGAGAAGGAAATTAAACCTGATGGTCGAATTTTTGCAAAGT





TGACTAAGAGAATGAGATCATGTCAAGTTATAGCAGAATCTCTTTTAGCGAACCATGCTGGGAAGTTA





ATGAAAGAGAATGGTGTTGTGATGAATCAGCTATCATTAACAAAATCACTATTAACAATGAGTCAGAT





TGGAATAATATCCGAGAAAGCTAGAAAATCGACTCGAGATAACATAAATCAACCTGGTTTCCAGAATA





TCCAGAGAAATAAATCACATCACTCCAAGCAAGTCAATCAGCGAGATCCAAGTGATGACTTTGAATTG





GCAGCATCTTTTTTAACTACTGATCTCAAAAAATATTGTTTACAATGGAGGTACCAGACAATTATCCCA





TTTGCTCAATCATTAAACAGAATGTATGGTTATCCTCATCTCTTTGAGTGGATTCACTTACGGCTAATG





CGTAGTACACTTTACGTGGGGGATCCCTTCAACCCACCAGCAGATACCAGTCAATTTGATCTAGATAA





AGTAATTAATGGAGATATCTTCATTGTATCACCCAGAGGTGGAATTGAAGGGCTATGTCAAAAGGCTT





GGACAATGATATCTATCTCTGTGATAATTCTATCTGCCACAGAGTCTGGCACACGAGTAATGAGTATG





GTGCAGGGAGATAATCAAGCAATTGCTGTCACCACACGAGTACCAAGGAGCCTGCCGACTCTTGAGA





AAAAGACTATTGCTTTTAGATCTTGTAATCTATTCTTTGAGAGGTTAAAATGTAATAATTTTGGATTAG





GTCACCATTTGAAAGAACAAGAGACTATCATTAGTTCTCACTTCTTTGTTTATAGCAAGAGAATATTCT





ATCAGGGGAGGATTCTAACGCAAGCCTTAAAAAATGCTAGTAAGCTCTGCTTGACAGCTGATGTCCTA





GGAGAATGTACCCAATCATCATGTTCTAATCTTGCAACTACTGTCATGAGGTTAACTGAGAATGGTGTT





GAAAAAGATATCTGTTTCTACTTGAATATCTATATGACCATCAAACAGCTCTCCTATGATATCATCTTC





CCTCAAGTGTCAATTCCTGGAGATCAGATCACATTAGAATACATAAATAATCCACACCTGGTATCACG





ATTGGCTCTTCTGCCATCCCAGCTAGGAGGTCTAAACTACCTGTCATGCAGTAGGCTGTTCAATCGAAA





CATAGGCGACCCGGTGGTTTCCGCAGTTGCAGATCTTAAGAGATTAATTAAATCAGGATGTATGGATT





ACTGGATCCTTTATAACTTATTAGGGAGAAAACCGGGAAACGGCTCATGGGCTACTTTAGCAGCTGAC





CCGTACTCAATCAATATAGAGTATCAATACCCCCCAACTACAGCTCTTAAGAGGCACACCCAACAAGC





TCTGATGGAACTCAGTACGAATCCAATGTTACGTGGCATATTCTCTGACAATGCACAGGCAGAAGAAA





ATAATCTTGCTAGATTTCTCCTGGATAGGGAGGTGATCTTTCCGCGTGTAGCTCACATCATCATTGAGC





AAACCAGTGTCGGGAGGAGAAAACAGATTCAAGGATATTTGGATTCAACTAGATCGATAATGAGTAA





ATCACTAGAAATTAAGCCCTTGTCCAATAGGAAGCTTAATGAAATACTGGATTACAACATCAATTACC





TAGCTTACAATTTGGCATTACTCAAGAATGCTATTGAACCTCCGACTTATTTGAAAGCAATGACTCTTG





AAACATGTAGCATCGACATTGCAAGGAGCCTCCGGAAGCTCTCCTGGGCCCCACTCTTGGGTGGGAGA





AATCTTGAAGGATTAGAGACGCCAGATCCCATTGAAATTACTGCAGGAGCATTAATTGTTGGATCGGG





CTACTGTGAACAGTGTGCTGCAGGAGACAATCGATTCACATGGTTTTTCTTGCCATCTGGTATCGAGAT





AGGAGGGGATCCCCGTGATAATCCTCCTATCCGTGTACCGTACATTGGCTCCAGGACTGATGAGAGGA





GGGTAGCCTCAATGGCATACATCAGGGGTGCCTCGAGTAGCCTAAAAGCAGTTCTTAGACTGGCGGGA





GTGTACATCTGGGCATTCGGAGATACTCTGGAGAATTGGATAGATGCACTGGATTTGTCTCACACTAG





AGTTAACATCACACTTGAACAGCTGCAATCCCTCACCCCACTTCCAACCTCTGCCAATCTAACCCATCG





GTTGGATGATGGCACAACTACCCTAAAGTTTACTCCTGCGAGCTCTTACACCTTTTCAAGTTTCACTCA





TATATCAAATGATGAGCAATACCTGACAATTAATGACAAAACTGCAGATTCAAATATAATCTACCAAC





AGTTAATGATCACTGGACTCGGAATTTTAGAAACATGGAATAATCCCCCAATCAATAGAACATTCGAA





GAATCTACCCTACATTTGCACACTGGTGCATCATGTTGTGTCCGACCTGTGGACTCCTGCATCATCTCA





GAAGCATTAACAGTCAAGCCACATATTACAGTACCGTACAGCAATAAATTTGTATTTGATGAAGACCC





GCTATCTGAATATGAGACTGCAAAACTGGAATCGTTATCATTTCAAGCCCAATTAGGCAACATTGATG





CTGTAGATATGACAGGTAAATTAACATTATTGTCCCAATTCACTGCAAGGCAGATTATTAATGCAATC





ACTGGACTCGATGAGTCTGTCTCTCTTACTAATGATGCCATTGTTGCATCAGACTATGTCTCCAATTGG





ATTAGTGAATGCATGTATACCAAATTAGATGAATTATTTATGTATTGTGGGTGGGAACTACTATTGGAA





CTATCCTATCAAATGTATTATCTGAGGGTAGTTGGGTGGAGTAATATAGTGGATTATTCTTACATGATC





TTGAGAAGAATCCCGGGTGCAGCATTAAACAATCTGGCATCTACATTAAGTCATCCAAAACTTTTCCG





ACGAGCTATCAACCTAGATATAGTTGCCCCCTTAAATGCTCCTCATTTTGCATCTCTGGACTACATCAA





GATGAGTGTGGATGCAATACTCTGGGGCTGTAAAAGAGTCATCAATGTGCTCTCCAATGGAGGGGACT





TAGAATTAGTTGTGACATCTGAAGATAGCCTTATTCTCAGTGACCGATCCATGAATCTCATTGCAAGGA





AATTAACTTTATTATCACTGATTCACCATAATGGTTTGGAACTACCAAAGATTAAGGGGTTCTCTCCTG





ATGAGAAGTGTTTCGCTTTGACAGAATTTTTGAGGAAAGTGGTGAACTCAGGGTTGAGTTCAATAGAG





AACCTATCAAATTTTATGTACAATGTGGAGAACCCACGGCTTGCAGCATTCGCCAGCAACAATTACTA





CCTGACCAGAAAATTATTGAATTCAATACGAGATACTGAGTCGGGTCAAGTAGCAGTCACCTCATATT





ATGAATCATTAGAATATATTGATAGTCTTAAGCTAACCCCACATGTGCCTGGTACCTCATGCATTGAGG





ATGATAGTCTATGTACAAATGATTACATAATCTGGATCATAGAGTCTAATGCAAACTTGGAGAAGTAT





CCAATTCCAAATAGCCCTGAGGATGATTCCAATTTCCATAACTTTAAGTTGAATGCTCCATCGCACCAT





ACCTTACGCCCATTAGGGTTGTCATCAACTGCTTGGTATAAGGGTATAAGCTGTTGCAGGTACCTTGAG





CGATTAAAGCTACCACAAGGTGATCATTTATATATTGCAGAAGGTAGTGGTGCCAGTATGACAATCAT





AGAATACCTATTCCCAGGAAGAAAGATATATTACAATTCTTTATTTAGTAGTGGTGACAATCCCCCAC





AAAGAAATTATGCACCAATGCCTACTCAGTTCATTGAGAGTGTCCCATACAAGCTCTGGCAAGCACAC





ACAGATCAATATCCCGAGATTTTTGAGGACTTCATCCCTCTATGGAACGGAAATGCCGCCATGACTGA





CATAGGAATGACAGCTTGTGTAGAATTCATCATCAATCGAGTCGGCCCAAGGACTTGCAGTTTAGTAC





ATGTAGATTTGGAATCAAGTGCAAGCTTAAATCAACAATGCCTGTCAAAGCCGATAATTAATGCTATC





ATCACTGCTACAACTGTTTTGTGCCCTCATGGGGTGCTTATTCTGAAATATAGTTGGTTGCCATTTACTA





GATTTAGTACTTTGATCACTTTCTTATGGTGCTACTTTGAGAGAATCACTGTTCTTAGGAGCACATATTC





TGGTCCAGCTAATCATGAGGTTTATTTAATTTGTATCCTTGCCAACAACTTTGCATTCCAGACTGTCTCG





CAGGCAACAGGAATGGCGATGACTTTAACCGATCAAGGGTTTACTTTGATATCACCTGAAAGAATAAA





TCAGTATTGGGATGGTCACTTGAAGCAAGAACGTATCGTAGCAGAAGCAATTGATAAGGTGGTTCTAG





GAGAAGATGCTCTATTCAATTCGAGTGATAATGAATTAATTCTCAAATGTGGAGGGACACCAAATGCA





CGGAATCTTATCGATATCGAGCCAGTCGCAACTTTCATAGAATTTGAACAACTGATCTGCACAATGTTG





ACAACCCACTTGAAGGAAATAATTGATATAACAAGGTCTGGAACCCAGGATTATGAAAGTTTATTACT





CACTCCTTACAATTTAGGTCTTCTTGGTAAAATCAGTACGATAGTGAGATTATTAACAGAAAGGATTCT





AAATCATACTATCAGGAATTGGTTGATCCTCCCACCTTCGCTCCGGATGATCGTGAAGCAGGACTTGG





AATTCGGCATATTCAGGATTACTTCCATCCTCAATTCTGATCGGTTCCTGAAGCTTTCTCCAAATAGGA





AATACTTGATTACACAATTAACTGCAGGCTACATTAGGAAATTGATTGAGGGGGATTGTAATATCGAT





CTAACCAGACCTATCCAAAAACAAATCTGGAAAGCATTAGGTTGTGTAGTCTATTGTCACGATCCAGT





AGATCAAAGGGAATCAACAGAGTTTATTGATATAAATATTAATGAAGAAATAGACCGCGGGATCGAT





GGCGAGGAAATCTAAATATATCAAGAATCAGAATTAGTTTAAGAAAAAAGAAGAGGATTAATCTTGG





TTTTCCCCTTGGT.






12. CVL60


The nucleic acid sequence for CVL60 is:










(SEQ ID NO: 72)



ACCAGGGGGAAAACGAAGTGGTGACTCAAATCATCGAAGACCCTCGAGATTACATAGGTCCGGAACC






TATGGCCTTCGTGACCGACCTCGAGTCAGAGTAGTTCAATAAGGACCTATCAAGTTTGGGCAATTTTTC





GTCCCCGACACAAAAATGTCATCCGTGCTTAAAGCATATGAGCGATTCACACTCACTCAAGAACTGCA





AGATCAGAGTGAGGAAGGTACAATCCCACCTACAACACTAAAACCGGTAATCAGGGTATTTATACTAA





CCTCTAATAACCCAGAGCTAAGATCCCGGCTTCTTCTATTCTGCCTACGGATTGTTCTCAGTAATGGTG





CAAGGGATTCCCATCGCTTTGGAGCATTACTTACAATGTTTTCGCTACCATCAGCCACAATGCTCAATC





ATGTCAAATTAGCTGACCAGTCACCAGAAGCTGATATCGAAAGGGTAGAGATCGATGGCTTTGAGGA





GGGATCATTCCGCTTAATCCCCAATGCTCGTTCAGGTATGAGCCGTGGAGAGATCAATGCCTATGCTG





CACTTGCAGAAGATCTACCTGACACACTAAACCATGCAACACCTTTTGTTGATTCCGAAGTCGAGGGA





ACTGCATGGGATGAGATTGAGACTTTCTTAGATATGTGTTACAGTGTCCTAATGCAGGCATGGATAGT





GACTTGCAAGTGCATGACTGCGCCAGACCAACCTGCTGCTTCTATTGAGAAACGCCTGCAAAAATATC





GTCAGCAAGGCAGGATCAACCCGAGATATCTCCTGCAACCGGAGGCTCGAAGAATAATCCAGAATGT





AATCCGAAAGGGAATGGTGGTCAGACATTTCCTCACCTTTGAACTGCAGCTTGCCCGAGCACAAAGCC





TTGTATCAAATAGGTATTATGCTATGGTAGGGGATGTTGGAAAGTATATAGAGAATTGTGGAATGGGA





GGCTTCTTTTTGACACTAAAATATGCATTAGGAACCAGATGGCCCACACTTGCTTTAGCTGCATTTTCA





GGAGAGCTAACAAAGCTAAAGTCCCTCATGGCATTATACCAGACCCTTGGTGAGCAGGCCCGATATTT





GGCCCTATTGGAGTCACCACATTTGATGGATTTTGCTGCAGCAAACTACCCACTGCTATATAGCTATGC





TATGGGAATAGGCTATGTGTTAGATGTCAACATGAGGAACTACGCTTTCTCCAGATCATACATGAATA





AGACATATTTCCAATTGGGAATGGAAACTGCAAGAAAACAACAGGGTGCAGTTGACATGAGGATGGC





AGAAGATCTCGGTCTAACTCAAGCCGAACGCACCGAGATGGCAAATACACTTGCCAAATTGACCACA





GCAAATCGAGGGGCAGACACCAGGGGAGGAGTCAACCCGTTCTCATCTATCACTGGGACAACTCAGG





TGCCCGCTGCAGCAACAGGTGACACATTCGAGAGTTACATGGCAGCGGATCGACTGAGGCAGAGATA





TGCTGATGCAGGCACCCACGATGATGAGATGCCACCATTGGAAGAGGAGGAAGAGGACGACACATCT





GCAGGTCCACGCACTGGACTAACTCTTGAACAAGTGGCCTTGGACATCCAGAACGCAGCAGTTGGAGC





TCCCATCCATACAGATGACCTGAATGCCGCACTGGGTGATCTTGACATCTAGACAATTCAGATCCCAA





TCTTAAATCGACACACCTAATTGACCAGTTAGATGGAACTACAGTGGATTCCATAAGGTTCCTGCCTAC





CATCGGCTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCCGATGCCAATAACA





CAATCCACAATCTACAATGGATCCCACTGATCTGAGCTTCTCCCCAGATGAGATCAATAAGCTCATAG





AGACAGGCCTGAATACTGTGGAGTATTTTACTTCCCAACAAGTCACAGGAACATCCTCTCTTGGAAAG





AATACAATACCACCAGGGGTCACAGGACTACTAACCAATGCTGCAGAGGCAAAGATCCAAGAGTCAA





CCAACCATCAGAAGGGTTCAGTTGGTGGGGGCGCAAAACCAAAGAAACCGCGACCAAAAATTGCCAT





TGTGCCAGCAGATGACAAAACGGTGCCCGGAAAGCCGATCCCAAACCCTCTATTAGGTCTGGACTCCA





CCCCGAGCACCCAAACTGTGCTTGATCTAAGTGGGAAAACATTACCATCAGGATCCTATAAGGGGGTT





AAACTTGCGAAATTTGGAAAAGAAAATCTGATGACACGGTTCATCGAGGAACCCAGAGAGAATCCTA





TCGCAACCAATTCCCCCATCGATTTTAAGAGGGGCAGGGATACCGGCGGGTTCCATAGAAGGGAGTAC





TCAATCGGATGGGTGGGAGATGAAGTCAAGGTCACTGAGTGGTGCAATCCATCCTGTTCTCCAATCAC





CGCTGCAGCAAGGCGATTTGAATGCACTTGTCACCAGTGTCCAGTCACTTGCTCTGAATGTGAACGAG





ATACTTAATACAGTGAGAAATTTGGACTCTCGGATGAATCAACTGGAGACAAAAGTAGATCGCATTCT





CTCATCTCAGTCTCTAATCCAGACCATCAAGAATGACATAGTTGGACTTAAAGCAGGGATGGCTACTT





TAGAAGGAATGATTACAACTGTGAAAATCATGGACCCGGGAGTTCCCAGTAATGTTACTGTGGAAGAT





GTACGCAAGAAACTAAGTAACCATGCTGTTGTTGTGCCAGAATCATTCAATGATAGTTTCTTGACTCAA





TCTGAAGATGTAATTTCACTTGATGAGTTGGCTCGACCAACTGCAACAAGTGTTAAGAAGATTGTCAG





GAAGGTTCCTCCTCAGAAGGATCTGACTGGATTGAAGATCACACTAGAGCAATTGGCAAAGGATTGCA





TCAGCAAACCGAAGATGAGGGAAGAGTATCTCCTCAAAATCAACCAGGCTTCCAGTGAGGCTCAGCT





AATTGACCTCAAGAAAGCAATCATCCGCAGTGCAATTTGATCAAGAAACACCCAATTACACTACACTG





GTATGACACTGTACTAACCCTGAGGGTTTTAGAAAAAACGATTAACGATAAATAAGCCCGAACACTAC





ACACCACCCGAGGCAGCCATGCCATCCATCAGCATCCCCGCAGACCCCACCAATCCACGTCAATCAAT





AAAAGCGTTCCCAATTGTGATCAACCGTGATGGGGGTGAGAAAGGTCGCTTGGTTAAACAACTACGCA





CAACCTACTTGAATGACCTAGATACTCATGAGCCACTGGTGACATTCGTAAATACTTATGGATTCATCT





ACGAACAGGATCGGGGAAATACCATTGTCGGAGAGGATCAACATGGGAAGAAAAGAGAGGCTGTGA





CTGCTGCAATGGTTACCCTTGGATGTGGGCCTAATCTACCATCATTAGGGAATGTCCTGGGACAACTG





AGTGAATTCCAGGTCATTGTTAGGAAGACATCCAGCAAAGCGGAAGAGATGGTCTTTGAAATTGTTAA





GTATCCGAGAATATTTCGGGGTCATACATTAATCCAGAAAGGACTAGTCTGTGTCTCCGCAGAAAAAT





TTGTTAAGTCACCAGGGAAAGTACAATCTGGAATGGACTATCTCTTCATTCCGACATTTCTGTCAGTGA





CTTACTGTCCAGCTGCAATCAAATTTCAGGTACCTGGCCCCATGTTGAAAATGAGATCAAGATACACT





CAGAGCTTACAACTTGAACTAATGATAAGAATCCTGTGTAAGCCCGATTCGCCACTTATGAAGGTCCA





TATCCCTGACAAGGAAGGAAGAGGATGTCTTGTATCAGTATGGTTGCATGTATGCAATATCTTCAAAT





CAGGAAACAAGAATGGCAGTGAGTGGCAGGAATACTGGATGAGAAAGTGTGCTAACATGCAACTTGA





AGTGTCGATTGCAGATATGTGGGGACCAACTATCATAATTCATGCCAGAGGTCACATTCCCAAAAGTG





CTAAGTTGTTTTTTGGAAAGGGTGGATGGAGCTGCCATCCACTTCACGAAGTTGTTCCAAGTGTCACTA





AAACACTATGGTCCGTGGGCTGTGAGATTACAAAGGCGAAGGCAATAATACAAGAGAGTAGCATCTC





TCTTCTCGTGGAGACTACTGACATCATAAGTCCAAAAGTCAAAATTTCATCTAAGCATCGCCGCTTTGG





GAAATCAAATTGGGGTCTGTTCAAGAAAACCAAATCACTGCCCAACCTGACGGAGCTGGAATGACTG





ACCCCCAATCGAGACTACACCACCTCAAACTATAGGTGGGTGGTACCTCAGTGATTAATCTCGTAAGC





ACTGATCGTAGGCTACAACACACTAATATTATCCAGATTAGAGAGCTTAATTAGCTCTGTATTAATAAT





AACACTACTATTCCAATAACTGGAATCACCAGCTTGATTTATCTCCAAAATGATTCAAAGAAAACAAA





TCATATTAAGACTATCCTAAGCACGAACCCATATCGTCCTTCAAATCATGGGTACTATAATTCAATTTC





TGGTGGTCTCCTGTCTATTGGCAGGAGCAGGCAGTCTTGATCCAGCAGCCCTCATGCAAATCGGTGTC





ATTCCAACAAATGTCCGGCAACTTATGTATTATACTGAGGCCTCATCAGCATTCATTGTTGTGAAGTTA





ATGCCTACAATTGACTCGCCGATTAGTGGATGTAATATAACATCAATTTCAAGCTATAATGCAACAGT





GACAAAACTCCTACAGCCGATCGGTGAGAATTTGGAGACGATTAGGAACCAGTTGATTCCAACTCGGA





GGAGACGCCGGTTTGCAGGGGTGGTGATTGGATTAGCTGCATTAGGAGTAGCTACTGCCGCACAGGTC





ACTGCCGCAGTAGCACTAGTAAAGGCAAATGAAAATGCTGCGGCTATACTCAATCTCAAAAATGCAAT





CCAAAAAACAAATGCAGCAGTTGCAGATGTGGTCCAGGCCACACAATCACTAGGAACaGCAGTTCAAG





CAGTTCAAGATCACATAAACAGTGTGGTAAGTCCAGCAATTACAGCAGCCAATTGTAAAGCCCAAGAT





GCTATCATTGGCTCAATCCTCAATCTCTATTTGACCGAGTTGACAACTATCTTCCACAATCAAATTACA





AACCCTGCATTGAGTCCTATTACAATTCAAGCTTTAAGGATCCTACTAGGGAGTACCTTGCCGACTGTG





GTCGAAAAATCTTTCAATACCCAGATAAGTGCGGCTGAGCTTCTCTCATCAGGGTTATTGACAGGCCA





GATTGTGGGATTAGATTTGACCTATATGCAGATGGTCATAAAAATTGAGCTGCCAACTTTAACTGTAC





AACCTGCAACCCAGATCATAGATCTGGCCACCATTTCTGCATTCATTAACAATCAAGAAGTCATGGCC





CAATTACCAACACGTGTTATTGTGACTGGCAGCTTGATCCAAGCCTATCCCGCATCGCAATGCACTATT





ACACCCAACACTGTGTACTGTAGGTATAATGATGCCCAAGTACTCTCAGATGATACGATGGCTTGCCT





CCAAGGTAACTTGACAAGATGCACCTTCTCTCCAGTGGTTGGGAGCTTTCTCACTCGATTCGTGCTGTT





CGATGGAATAGTTTATGCAAATTGCAGGTCGATGTTGTGCAAGTGCATGCAGCCTGCTGCTGTGATCCT





ACAGCCGAGTTCATCCCCTGTAACTGTCATTGACATGTACAAATGTGTGAGTCTGCAGCTTGACAATCT





CAGATTCACCATCACTCAATTGGCCAATGTAACCTACAATAGCACCATCAAGCTTGAAACATCCCAGA





TCTTGCCTATTGATCCGTTGGATATATCCCAGAATCTAGCTGCGGTGAATAAGAGTCTAAGTGATGCAC





TACAACACTTAGCACAAAGTGACACATACCTTTCTGCAATCACATCAGCTACGACTACAAGTGTATTA





TCCATAATAGCAATCTGTCTTGGATCGTTAGGTTTAATATTAATAATCTTGCTCAGTGTAGTTGTGTGG





AAGTTATTGACCATTGTCGCTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAATTCAGCATTC





CACCACTCACGATCTGATCTCAGTGAGAAAAATCAACCTGCAACTCTTGGAACAAGATAAGACAGTCA





TCCATTAGTAATTTTTAAGAAAAAAACGATAGGACCGAAACTAGTATTGAAAGAACCGTCTCGGTCAA





TCTAGGTAATCGAGCTGcTACCGTCTCGGAAAGCTCAAATCATGCTGCCTGATCCGGAAGATCCGGAA





AGCAAAAAAGCTACAAGGAGAACAGGAAACCTAATTATCTGCTTCCTATTCATCTTCTTTCCGTTTGTA





AACTTCATTGTTCCAACTCTAAGACACTTGCTGTCCTAACACCTGCTATAGGCTATCCACTGCATCATC





TCTTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCCGGTGCCAACAACACAAT





CCACAATCTACAGTCGACGCGGCCGCCatgttcgtcttcctggtcctgctgcctctggtctcctcacag





tgcgtcaatctgagaactcggactcagctgccacctgcttatactaatagcttcaccagaggcgtgtact





atcctgacaaggtgtttagaagctccgtgctgcactctacacaggatctgtttctgccattctttagcaa





cgtgacctggttccacgccatccacgtgagcggcaccaatggcacaaagcggttcgacaatcccgtgc





tgccttttaacgatggcgtgtacttcgcctctaccgagaagagcaacatcatcagaggctggatctttg





gcaccacactggactccaagacacagtctctgctgatcgtgaacaatgccaccaacgtggtcatcaagg





tgtgcgagttccagttttgtaatgatcccttcctgggcgtgtactatcacaagaacaataagagctgg





atggagtccggcgtgtattctagcgccaacaactgcacatttgagtacgtgagccagcctttcctgatgg





acctggagggcaagcagggcaatttcaagaacctgagggagttcgtgtttaagaatatcgacggctactt





caaaatctactctaagcacacccccatcaacctggtgcgcgacctgcctcagggcttcagcgccctgga





gcccctggtggatctgcctatcggcatcaacatcacccggtttcagacactgctggccctgcacagaa





gctacctgacacccggcgactcctctagcggatggaccgccggcgctgccgcctactatgtgggctac





ctccagccccggaccttcctgctgaagtacaacgagaatggcaccatcacagacgcagtggattgcgc





cctggaccccctgagcgagacaaagtgtacactgaagtcctttaccgtggagaagggcatctatcagac





atccaatttcagggtgcagccaaccgagtctatcgtgcgctttcctaatatcacaaacctgtgcccattt





ggcgaggtgttcaacgcaacccgcttcgccagcgtgtacgcctggaataggaagcggatcagcaactgcg





tggccgactatagcgtgctgtacaactccgcctctttcagcacctttaagtgctatggcgtgtccccca





caaagctgaatgacctgtgctttaccaacgtctacgccgattctttcgtgatcaggggcgacgaggtgc





gccagatcgcccccggccagacaggcaagatcgcagactacaattataagctgccagacgatttcacc





ggctgcgtgatcgcctggaacagcaacaatctggattccaaagtgggcggcaactacaattatagatac





cggctgtttagaaagagcaatctgaagcccttcgagagggacatctctacagaaatctaccaggccggca





gcaagccttgcaatggcgtggagggctttaactgttatttcccactccagtcctacggcttccagccca





caaacggcgtgggctatcagccttaccgcgtggtggtgctgagctttgagctgctgcacgccccagcaa





cagtgtgcggccccaagaagtccaccaatctggtgaagaacaagtgcgtgaacttcaacttcaacggcc





tgaccggcacaggcgtgctgaccgagtccaacaagaagttcctgccatttcagcagttcggcagggac





atcgcagataccacagacgccgtgcgcgacccacagaccctggagatcctggacatcacaccctgctctt





tcggcggcgtgagcgtgatcacacccggcaccaatacaagcaaccaggtggccgtgctgtatcagggc





gtgaattgtaccgaggtgcccgtggctatccacgccgatcagctgaccccaacatggcgggtgtacagc





accggctccaacgtcttccagacaagagccggatgcctgatcggagcagagcacgtgaacaattccta





tgagtgcgacatcccaatcggcgccggcatctgtgcctcttaccagacccagacaaactctagaagaa





gagcccggagcgtggcctcccagtctatcatcgcctataccatgtccctgggcgccgagaacagcgtggc





ctactctaacaatagcatcgccatcccaaccaacttcacaatctctgtgaccacagagatcctgcccgtg





tccatgaccaagacatctgtggactgcacaatgtatatctgtggcgattctaccgagtgcagcaacct





gctgctccagtacggcagcttttgtacccagctgaatagagccctgacaggcatcgccgtggagcagga





taagaacacacaggaggtgttcgcccaggtgaagcaaatctacaagaccccccctatcaaggactttggc





ggcttcaatttttcccagatcctgcctgatccatccaagccttctaagcggagctttatcgaggacctgc





tgttcaacaaggtgaccctggccgatgccggcttcatcaagcagtatggcgattgcctgggcgacatcgc





agccagggacctgatctgcgcccagaagtttaatggcctgaccgtgctgccacccctgctgacagatgag





atgatcgcacagtacacaagcgccctgctggccggcaccatcacatccggatggaccttcggcgcaggag





ccgccctccagatcccctttgccatgcagatggcctataggttcaacggcatcggcgtgacccagaatgt





gctgtacgagaaccagaagctgatcgccaatcagtttaactccgccatcggcaagatccaggacagcct





gtcctctacagccagcgccctgggcaagctccagaacgtggtgaatcagaacgcccaggccctgaatacc





ctggtgaagcagctgagcagcaacttcggcgccatctctagcgtgctgaatgacatcctgagccggctgg





acaaggtggaggcagaggtgcagatcgaccggctgatcaccggccggctccagagcctccagacctatgt





gacacagcagctgatcagggccgccgagatcagggccagcgccaatctggcagcaaccaagatgtccgag





tgcgtgctgggccagtctaagagagtggacttttgtggcaagggctatcacctgatgtccttccctcag





tctgccccacacggcgtggtgtttctgcacgtgacctacgtgcccgcccaggagaagaacttcaccacag





cccctgccatctgccacgatggcaaggcccactttccaagggagggcgtgttcgtgtccaacggcaccca





ctggtttgtgacacagcgcaatttctacgagccccagatcatcaccacagacaacaccttcgtgagcggc





aactgtgacgtggtcatcggcatcgtgaacaataccgtgtatgatccactccagcccgagctggacagct





ttaaggaggagctggataagtatttcaagaatcacacctcccctgacgtggatctgggcgacatcagcgg





catcaatgcctccgtggtgaacatccagaaggagatcgaccgcctgaacgaggtggctaagaatctgaa





cgagagcctgatcgacctccaggagctgggcaagtatgagcagtacatcaagtggccctggtacatctgg





ctgggcttcatcgccggcctgatcgccatcgtgatggtgaccatcatgctgtgctgtatgacatcctgct





gttcttgcctgaagggctgctgtagctgtggctcctgctgtAAGTTATTGACCATTGTCGTTGCTAATCG





AAATAGAATGGAGAATTTTGTTTATCATAAATGAGCTAGCCTCCTGCCATACTTCCTACTCACATCATA





TCTATTTTAAAGAAAAAATAGGCCCGAACACTAATCGTGCCGGCAGTGCCACTGCACACACAACACTA





CACATACAATACACTACAATGGTTGCAGAAGATGCCCCTGTTAGGGGCACTTGCCGAGTATTATTTCG





AACAACAACTTTAATTTTTCTATGCACACTATTAGCATTAAGCATCTCTATCCTTTATGAGAGTTTAAT





AACCCAAAAGCAAATCATGAGCCAAGCAGGCTCAACTGGATCTAATTCTAGATTAGGAAGTATCACTG





ATCTTCTTAATAATATTCTCTCTGTCGCAAATCAGATTATATATAACTCTGCAGTCGCTCTACCTCTACA





ATTGGACACTCTTGAATCAACACTCCTTACAGCCATTAAGTCTCTTCAAACAAGTGACAAGCTAGAAC





AGAACTGCTCGTGGGGTGCTGCACTGATTAATGATAATAGATACATTAATGGCATCAATCAGTTCTATT





TCTCAATTGCTGAGGGTCGCAAGCTGACACTTGGCCCACTTCTTAATATACCTAGTTTCATTCCAACTG





CCACGACACCAGAGGGCTGCACCAGGATCCCATCATTCTCGCTCACCAAGACACACTGGTGTTATACA





CACAATGTTATCCTGAATGGATGCCAGGATCATGTATCCTCAAATCAATTTGTTTCCATGGGAATCATT





GAACCCACTTCTGCCGGGTTTCCATCCTTTCGAACCCTAAAGACTCTATATCTCAGCGATGGGGTCAAT





CGTAAGAGCTGCTCTATCAGTACAGTTCCGGGGGGTTGTATGATGTACTGTTTCGTCTCTACTCAACCA





GAGAGGGATGACTACTTTTCTACCGCTCCTCCAGAACAACGAATTATTATAATGTACTATAATGATAC





AATCGTGGAGCGCATAATTAATCCACCCGGGGTACTAGATGTATGGGCAACATTGAACCCAGGAACA





GGAAGCGGGGTATATTATTTAGGTTGGGTACTCTTTCCAATATATGGCGGCGTGATTAAAGATACGAG





TTTATGGAATAATCAAGCAAATAAATACTTTATCCCCCAGATGGTTGCTGCTCTCTGCTCACAAAACCA





GGCAACTCAAGTCCAAAATGCTAAGTCATCATACTATAGCAGCTGGTTTGGCAATCGAATGATTCAGT





CTGGGATCCTGGCATGTCCTCTTCAACAGGATCTAACCAATGAGTGTTTAGTTCTGCCCTTTTCTAATG





ATCAGGTGCTTATGGGTGCTGAAGGGAGATTATACATGTATGGTGACTCGGTGTATTACTACCAAAGA





AGCAATAGTTGGTGGCCTATGACCATGCTGTATAAGGTAACCATAACATTCACTAATGGTCAGCCATC





TGCTATATCAGCTCAGAATGTGCCCACACAGCAGGTCCCTAGACCTGGGACAGGAAGCTGCTCTGCAA





CAAATAGATGTCCCGGTTTTTGCTTGAAAGGAGTGTATGCTGATGCCTGGTTACTGACCAACCCTTCGT





CTACCAGTACATTTGGATCAGAAGCAACCTTCACTGGTTCTTATCTCAACGCAGCAACTCAGCGTATCA





ATCCGACGATGTATATCGCGAACAACACACAGATCATAAGCTCACAGCAATTTGGATCAAGCGGTCAA





GAAGCAGCATATGGCCACACAACTTGTTTTAGGGACACAGGCTCTGTTATGGTATACTGTATCTATATT





ATTGAATTGTCCTCATCTCTCTTAGGACAATTTCAGATTGTCCCATTTATCCGTCAGGTGACACTATCCT





AAAGGCAGAAGCCTCCAGGTCTGACCCAGCCAATCAAAGCATTATACCAGACCATGGAATGCATACC





AAACATTATTGACACTAATGACACACAAAATTGGTTTTAAGAAAAACCAAGAGAACAATAGGCCAGA





ATGGCTGGGTCTCGGGAGATATTACTCCCTGAAGTCCATCTCAATTCACCAATTGTAAAGCATAAGCT





ATACTATTACATTCTACTTGGAAACCTCCCAAATGAGATCGACATTGACGATTTAGGTCCATTACATAA





TCAAAATTGGAATCAAATAGCACATGAAGAGTCTAACTTAGCCCAACGCTTGGTAAATGTAAGAAATT





TTCTAATTACCCACATCCCTGATCTTAGAAAGGGCCATTGGCAAGAGTATGTCAATGTAATACTGTGGC





CGCGAATTCTTCCCTTGATCCCGGATTTTAAAATCAATGACCAATTGCCTCTACTCAAAAATTGGGACA





AGTTAGTTAAAGAATCATGTTCAGTAATCAATGCGGGTACTTCCCAGTGCATTCAGAATCTCAGCTATG





GACTGACAGGTCGTGGGAACCTCTTTACACGATCACGTGAACTCTCTGGTGACCGCAGGGATATTGAT





CTTAAGACGGTTGTGGCAGCATGGCATGACTCAGACTGGAAAAGAATAAGTGATTTTTGGATTATGAT





CAAATTCCAGATGAGACAATTAATTGTTAGGCAAACAGATCATAATGATCCTGATTTAATCACGTATA





TCGAAAATAGAGAAGGCATAATCATCATAACCCCTGAACTGGTAGCATTATTTAACACTGAGAATCAT





ACACTAACATACATGACCTTTGAAATTGTACTGATGGTTTCAGATATGTACGAAGGTCGTCACAACATT





TTATCACTATGCACAGTTAGCACTTACCTGAATCCTCTGAAGAAAAGAATAACATATTTATTGAGCCTT





GTAGATAACTTAGCTTTTCAGATAGGTGATGCTGTATATAACATAATTGCTTTGCTAGAATCCTTTGTA





TATGCACAGTTGCAAATGTCAGATCCCATCCCAGAACTCAGAGGACAATTCCATGCATTCGTATGTTCT





GAGATTCTTGATGCACTAAGGGGAACTAATAGTTTCACCCAGGATGAATCAAGAACTGTGACAACCAA





TTTGATATCCCCATTCCAAGATCTGACCCCAGATCTTACGGCTGAATTGCTCTGTATAATGAGGCTTTG





GGGACACCCCATGCTCACCGCCAGTCAAGCTGCGGGAAAGGTACGCGAGTCCATGTGTGCTGGAAAA





GTATTAGACTTTCCCACCATTATGAAAACACTAGCCTTTTTCCATACTATTCTGATCAATGGATACAGG





AGGAAGCATCATGGAGTATGGCCACCCTTAAACTTACCGGGTAATGCTTCAAAGGGTCTCACGGAACT





TATGAATGACAATACTGAGATAAGCTATGAATTCACACTTAAGCATTGGAAGGAAATCTCTCTTATAA





AATTCAAGAAATGTTTTGATGCAGACGCAGGTGAGGAACTCAGTATATTTATGAAAGATAAAGCAATT





AGTGCCCCAAAACAAGATTGGATGAGTGTGTTTAGAAGAAGCCTAATCAAACAGCGCCATCAGCATC





ATCAGGTCCCCCTACCAAATCCATTCAATCGACGGCTATTGCTAAACTTTCTCGGAGATGACAAATTCG





ACCCGAATGTGGAGCTACAGTATGTAACATCAGGTGAGTATCTACATGATGACACGTTTTGTGCATCA





TATTCACTAAAAGAGAAGGAAATTAAACCTGATGGTCGAATTTTTGCAAAGTTGACTAAGAGAATGAG





ATCATGTCAAGTTATAGCAGAATCTCTTTTAGCGAACCATGCTGGGAAGTTAATGAAAGAGAATGGTG





TTGTGATGAATCAGCTATCATTAACAAAATCACTATTAACAATGAGTCAGATTGGAATAATATCCGAG





AAAGCTAGAAAATCGACTCGAGATAACATAAATCAACCTGGTTTCCAGAATATCCAGAGAAATAAAT





CACATCACTCCAAGCAAGTCAATCAGCGAGATCCAAGTGATGACTTTGAATTGGCAGCATCTTTTTTA





ACTACTGATCTCAAAAAATATTGTTTACAATGGAGGTACCAGACAATTATCCCATTTGCTCAATCATTA





AACAGAATGTATGGTTATCCTCATCTCTTTGAGTGGATTCACTTACGGCTAATGCGTAGTACACTTTAC





GTGGGGGATCCCTTCAACCCACCAGCAGATACCAGTCAATTTGATCTAGATAAAGTAATTAATGGAGA





TATCTTCATTGTATCACCCAGAGGTGGAATTGAAGGGCTATGTCAAAAGGCTTGGACAATGATATCTA





TCTCTGTGATAATTCTATCTGCCACAGAGTCTGGCACACGAGTAATGAGTATGGTGCAGGGAGATAAT





CAAGCAATTGCTGTCACCACACGAGTACCAAGGAGCCTGCCGACTCTTGAGAAAAAGACTATTGCTTT





TAGATCTTGTAATCTATTCTTTGAGAGGTTAAAATGTAATAATTTTGGATTAGGTCACCATTTGAAAGA





ACAAGAGACTATCATTAGTTCTCACTTCTTTGTTTATAGCAAGAGAATATTCTATCAGGGGAGGATTCT





AACGCAAGCCTTAAAAAATGCTAGTAAGCTCTGCTTGACAGCTGATGTCCTAGGAGAATGTACCCAAT





CATCATGTTCTAATCTTGCAACTACTGTCATGAGGTTAACTGAGAATGGTGTTGAAAAAGATATCTGTT





TCTACTTGAATATCTATATGACCATCAAACAGCTCTCCTATGATATCATCTTCCCTCAAGTGTCAATTCC





TGGAGATCAGATCACATTAGAATACATAAATAATCCACACCTGGTATCACGATTGGCTCTTCTGCCATC





CCAGCTAGGAGGTCTAAACTACCTGTCATGCAGTAGGCTGTTCAATCGAAACATAGGCGACCCGGTGG





TTTCCGCAGTTGCAGATCTTAAGAGATTAATTAAATCAGGATGTATGGATTACTGGATCCTTTATAACT





TATTAGGGAGAAAACCGGGAAACGGCTCATGGGCTACTTTAGCAGCTGACCCGTACTCAATCAATATA





GAGTATCAATACCCCCCAACTACAGCTCTTAAGAGGCACACCCAACAAGCTCTGATGGAACTCAGTAC





GAATCCAATGTTACGTGGCATATTCTCTGACAATGCACAGGCAGAAGAAAATAATCTTGCTAGATTTC





TCCTGGATAGGGAGGTGATCTTTCCGCGTGTAGCTCACATCATCATTGAGCAAACCAGTGTCGGGAGG





AGAAAACAGATTCAAGGATATTTGGATTCAACTAGATCGATAATGAGTAAATCACTAGAAATTAAGCC





CTTGTCCAATAGGAAGCTTAATGAAATACTGGATTACAACATCAATTACCTAGCTTACAATTTGGCATT





ACTCAAGAATGCTATTGAACCTCCGACTTATTTGAAAGCAATGACTCTTGAAACATGTAGCATCGACA





TTGCAAGGAGCCTCCGGAAGCTCTCCTGGGCCCCACTCTTGGGTGGGAGAAATCTTGAAGGATTAGAG





ACGCCAGATCCCATTGAAATTACTGCAGGAGCATTAATTGTTGGATCGGGCTACTGTGAACAGTGTGC





TGCAGGAGACAATCGATTCACATGGTTTTTCTTGCCATCTGGTATCGAGATAGGAGGGGATCCCCGTG





ATAATCCTCCTATCCGTGTACCGTACATTGGCTCCAGGACTGATGAGAGGAGGGTAGCCTCAATGGCA





TACATCAGGGGTGCCTCGAGTAGCCTAAAAGCAGTTCTTAGACTGGCGGGAGTGTACATCTGGGCATT





CGGAGATACTCTGGAGAATTGGATAGATGCACTGGATTTGTCTCACACTAGAGTTAACATCACACTTG





AACAGCTGCAATCCCTCACCCCACTTCCAACCTCTGCCAATCTAACCCATCGGTTGGATGATGGCACA





ACTACCCTAAAGTTTACTCCTGCGAGCTCTTACACCTTTTCAAGTTTCACTCATATATCAAATGATGAG





CAATACCTGACAATTAATGACAAAACTGCAGATTCAAATATAATCTACCAACAGTTAATGATCACTGG





ACTCGGAATTTTAGAAACATGGAATAATCCCCCAATCAATAGAACATTCGAAGAATCTACCCTACATT





TGCACACTGGTGCATCATGTTGTGTCCGACCTGTGGACTCCTGCATCATCTCAGAAGCATTAACAGTCA





AGCCACATATTACAGTACCGTACAGCAATAAATTTGTATTTGATGAAGACCCGCTATCTGAATATGAG





ACTGCAAAACTGGAATCGTTATCATTTCAAGCCCAATTAGGCAACATTGATGCTGTAGATATGACAGG





TAAATTAACATTATTGTCCCAATTCACTGCAAGGCAGATTATTAATGCAATCACTGGACTCGATGAGTC





TGTCTCTCTTACTAATGATGCCATTGTTGCATCAGACTATGTCTCCAATTGGATTAGTGAATGCATGTA





TACCAAATTAGATGAATTATTTATGTATTGTGGGTGGGAACTACTATTGGAACTATCCTATCAAATGTA





TTATCTGAGGGTAGTTGGGTGGAGTAATATAGTGGATTATTCTTACATGATCTTGAGAAGAATCCCGG





GTGCAGCATTAAACAATCTGGCATCTACATTAAGTCATCCAAAACTTTTCCGACGAGCTATCAACCTA





GATATAGTTGCCCCCTTAAATGCTCCTCATTTTGCATCTCTGGACTACATCAAGATGAGTGTGGATGCA





ATACTCTGGGGCTGTAAAAGAGTCATCAATGTGCTCTCCAATGGAGGGGACTTAGAATTAGTTGTGAC





ATCTGAAGATAGCCTTATTCTCAGTGACCGATCCATGAATCTCATTGCAAGGAAATTAACTTTATTATC





ACTGATTCACCATAATGGTTTGGAACTACCAAAGATTAAGGGGTTCTCTCCTGATGAGAAGTGTTTCGC





TTTGACAGAATTTTTGAGGAAAGTGGTGAACTCAGGGTTGAGTTCAATAGAGAACCTATCAAATTTTA





TGTACAATGTGGAGAACCCACGGCTTGCAGCATTCGCCAGCAACAATTACTACCTGACCAGAAAATTA





TTGAATTCAATACGAGATACTGAGTCGGGTCAAGTAGCAGTCACCTCATATTATGAATCATTAGAATA





TATTGATAGTCTTAAGCTAACCCCACATGTGCCTGGTACCTCATGCATTGAGGATGATAGTCTATGTAC





AAATGATTACATAATCTGGATCATAGAGTCTAATGCAAACTTGGAGAAGTATCCAATTCCAAATAGCC





CTGAGGATGATTCCAATTTCCATAACTTTAAGTTGAATGCTCCATCGCACCATACCTTACGCCCATTAG





GGTTGTCATCAACTGCTTGGTATAAGGGTATAAGCTGTTGCAGGTACCTTGAGCGATTAAAGCTACCA





CAAGGTGATCATTTATATATTGCAGAAGGTAGTGGTGCCAGTATGACAATCATAGAATACCTATTCCC





AGGAAGAAAGATATATTACAATTCTTTATTTAGTAGTGGTGACAATCCCCCACAAAGAAATTATGCAC





CAATGCCTACTCAGTTCATTGAGAGTGTCCCATACAAGCTCTGGCAAGCACACACAGATCAATATCCC





GAGATTTTTGAGGACTTCATCCCTCTATGGAACGGAAATGCCGCCATGACTGACATAGGAATGACAGC





TTGTGTAGAATTCATCATCAATCGAGTCGGCCCAAGGACTTGCAGTTTAGTACATGTAGATTTGGAATC





AAGTGCAAGCTTAAATCAACAATGCCTGTCAAAGCCGATAATTAATGCTATCATCACTGCTACAACTG





TTTTGTGCCCTCATGGGGTGCTTATTCTGAAATATAGTTGGTTGCCATTTACTAGATTTAGTACTTTGAT





CACTTTCTTATGGTGCTACTTTGAGAGAATCACTGTTCTTAGGAGCACATATTCTGGTCCAGCTAATCA





TGAGGTTTATTTAATTTGTATCCTTGCCAACAACTTTGCATTCCAGACTGTCTCGCAGGCAACAGGAAT





GGCGATGACTTTAACCGATCAAGGGTTTACTTTGATATCACCTGAAAGAATAAATCAGTATTGGGATG





GTCACTTGAAGCAAGAACGTATCGTAGCAGAAGCAATTGATAAGGTGGTTCTAGGAGAAGATGCTCTA





TTCAATTCGAGTGATAATGAATTAATTCTCAAATGTGGAGGGACACCAAATGCACGGAATCTTATCGA





TATCGAGCCAGTCGCAACTTTCATAGAATTTGAACAACTGATCTGCACAATGTTGACAACCCACTTGA





AGGAAATAATTGATATAACAAGGTCTGGAACCCAGGATTATGAAAGTTTATTACTCACTCCTTACAAT





TTAGGTCTTCTTGGTAAAATCAGTACGATAGTGAGATTATTAACAGAAAGGATTCTAAATCATACTATC





AGGAATTGGTTGATCCTCCCACCTTCGCTCCGGATGATCGTGAAGCAGGACTTGGAATTCGGCATATTC





AGGATTACTTCCATCCTCAATTCTGATCGGTTCCTGAAGCTTTCTCCAAATAGGAAATACTTGATTACA





CAATTAACTGCAGGCTACATTAGGAAATTGATTGAGGGGGATTGTAATATCGATCTAACCAGACCTAT





CCAAAAACAAATCTGGAAAGCATTAGGTTGTGTAGTCTATTGTCACGATCCAGTAGATCAAAGGGAAT





CAACAGAGTTTATTGATATAAATATTAATGAAGAAATAGACCGCGGGATCGATGGCGAGGAAATCTA





AATATATCAAGAATCAGAATTAGTTTAAGAAAAAAGAAGAGGATTAATCTTGGTTTTCCCCTTGGT.






13. CVL64


The nucleic acid sequence for CVL64 is:










(SEQ ID NO: 73)



ACCAGGGGGAAAACGAAGTGGTGACTCAAATCATCGAAGACCCTCGAGATTACATAGGTCCGGAACC






TATGGCCTTCGTGACCGACCTCGAGTCAGAGTAGTTCAATAAGGACCTATCAAGTTTGGGCAATTTTTC





GTCCCCGACACAAAAATGTCATCCGTGCTTAAAGCATATGAGCGATTCACACTCACTCAAGAACTGCA





AGATCAGAGTGAGGAAGGTACAATCCCACCTACAACACTAAAACCGGTAATCAGGGTATTTATACTAA





CCTCTAATAACCCAGAGCTAAGATCCCGGCTTCTTCTATTCTGCCTACGGATTGTTCTCAGTAATGGTG





CAAGGGATTCCCATCGCTTTGGAGCATTACTTACAATGTTTTCGCTACCATCAGCCACAATGCTCAATC





ATGTCAAATTAGCTGACCAGTCACCAGAAGCTGATATCGAAAGGGTAGAGATCGATGGCTTTGAGGA





GGGATCATTCCGCTTAATCCCCAATGCTCGTTCAGGTATGAGCCGTGGAGAGATCAATGCCTATGCTG





CACTTGCAGAAGATCTACCTGACACACTAAACCATGCAACACCTTTTGTTGATTCCGAAGTCGAGGGA





ACTGCATGGGATGAGATTGAGACTTTCTTAGATATGTGTTACAGTGTCCTAATGCAGGCATGGATAGT





GACTTGCAAGTGCATGACTGCGCCAGACCAACCTGCTGCTTCTATTGAGAAACGCCTGCAAAAATATC





GTCAGCAAGGCAGGATCAACCCGAGATATCTCCTGCAACCGGAGGCTCGAAGAATAATCCAGAATGT





AATCCGAAAGGGAATGGTGGTCAGACATTTCCTCACCTTTGAACTGCAGCTTGCCCGAGCACAAAGCC





TTGTATCAAATAGGTATTATGCTATGGTAGGGGATGTTGGAAAGTATATAGAGAATTGTGGAATGGGA





GGCTTCTTTTTGACACTAAAATATGCATTAGGAACCAGATGGCCCACACTTGCTTTAGCTGCATTTTCA





GGAGAGCTAACAAAGCTAAAGTCCCTCATGGCATTATACCAGACCCTTGGTGAGCAGGCCCGATATTT





GGCCCTATTGGAGTCACCACATTTGATGGATTTTGCTGCAGCAAACTACCCACTGCTATATAGCTATGC





TATGGGAATAGGCTATGTGTTAGATGTCAACATGAGGAACTACGCTTTCTCCAGATCATACATGAATA





AGACATATTTCCAATTGGGAATGGAAACTGCAAGAAAACAACAGGGTGCAGTTGACATGAGGATGGC





AGAAGATCTCGGTCTAACTCAAGCCGAACGCACCGAGATGGCAAATACACTTGCCAAATTGACCACA





GCAAATCGAGGGGCAGACACCAGGGGAGGAGTCAACCCGTTCTCATCTATCACTGGGACAACTCAGG





TGCCCGCTGCAGCAACAGGTGACACATTCGAGAGTTACATGGCAGCGGATCGACTGAGGCAGAGATA





TGCTGATGCAGGCACCCACGATGATGAGATGCCACCATTGGAAGAGGAGGAAGAGGACGACACATCT





GCAGGTCCACGCACTGGACTAACTCTTGAACAAGTGGCCTTGGACATCCAGAACGCAGCAGTTGGAGC





TCCCATCCATACAGATGACCTGAATGCCGCACTGGGTGATCTTGACATCTAGACAATTCAGATCCCAA





TCTTAAATCGACACACCTAATTGACCAGTTAGATGGAACTACAGTGGATTCCATAAGGTTCCTGCCTAC





CATCGGCTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCCGATGCCAATAACA





CAATCCACAATCTACAATGGATCCCACTGATCTGAGCTTCTCCCCAGATGAGATCAATAAGCTCATAG





AGACAGGCCTGAATACTGTGGAGTATTTTACTTCCCAACAAGTCACAGGAACATCCTCTCTTGGAAAG





AATACAATACCACCAGGGGTCACAGGACTACTAACCAATGCTGCAGAGGCAAAGATCCAAGAGTCAA





CCAACCATCAGAAGGGTTCAGTTGGTGGGGGCGCAAAACCAAAGAAACCGCGACCAAAAATTGCCAT





TGTGCCAGCAGATGACAAAACGGTGCCCGGAAAGCCGATCCCAAACCCTCTATTAGGTCTGGACTCCA





CCCCGAGCACCCAAACTGTGCTTGATCTAAGTGGGAAAACATTACCATCAGGATCCTATAAGGGGGTT





AAACTTGCGAAATTTGGAAAAGAAAATCTGATGACACGGTTCATCGAGGAACCCAGAGAGAATCCTA





TCGCAACCAATTCCCCCATCGATTTTAAGAGGGGCAGGGATACCGGCGGGTTCCATAGAAGGGAGTAC





TCAATCGGATGGGTGGGAGATGAAGTCAAGGTCACTGAGTGGTGCAATCCATCCTGTTCTCCAATCAC





CGCTGCAGCAAGGCGATTTGAATGCACTTGTCACCAGTGTCCAGTCACTTGCTCTGAATGTGAACGAG





ATACTTAATACAGTGAGAAATTTGGACTCTCGGATGAATCAACTGGAGACAAAAGTAGATCGCATTCT





CTCATCTCAGTCTCTAATCCAGACCATCAAGAATGACATAGTTGGACTTAAAGCAGGGATGGCTACTT





TAGAAGGAATGATTACAACTGTGAAAATCATGGACCCGGGAGTTCCCAGTAATGTTACTGTGGAAGAT





GTACGCAAGAAACTAAGTAACCATGCTGTTGTTGTGCCAGAATCATTCAATGATAGTTTCTTGACTCAA





TCTGAAGATGTAATTTCACTTGATGAGTTGGCTCGACCAACTGCAACAAGTGTTAAGAAGATTGTCAG





GAAGGTTCCTCCTCAGAAGGATCTGACTGGATTGAAGATCACACTAGAGCAATTGGCAAAGGATTGCA





TCAGCAAACCGAAGATGAGGGAAGAGTATCTCCTCAAAATCAACCAGGCTTCCAGTGAGGCTCAGCT





AATTGACCTCAAGAAAGCAATCATCCGCAGTGCAATTTGATCAAGAAACACCCAATTACACTACACTG





GTATGACACTGTACTAACCCTGAGGGTTTTAGAAAAAACGATTAACGATAAATAAGCCCGAACACTAC





ACACCACCCGAGGCAGCCATGCCATCCATCAGCATCCCCGCAGACCCCACCAATCCACGTCAATCAAT





AAAAGCGTTCCCAATTGTGATCAACCGTGATGGGGGTGAGAAAGGTCGCTTGGTTAAACAACTACGCA





CAACCTACTTGAATGACCTAGATACTCATGAGCCACTGGTGACATTCGTAAATACTTATGGATTCATCT





ACGAACAGGATCGGGGAAATACCATTGTCGGAGAGGATCAACATGGGAAGAAAAGAGAGGCTGTGA





CTGCTGCAATGGTTACCCTTGGATGTGGGCCTAATCTACCATCATTAGGGAATGTCCTGGGACAACTG





AGTGAATTCCAGGTCATTGTTAGGAAGACATCCAGCAAAGCGGAAGAGATGGTCTTTGAAATTGTTAA





GTATCCGAGAATATTTCGGGGTCATACATTAATCCAGAAAGGACTAGTCTGTGTCTCCGCAGAAAAAT





TTGTTAAGTCACCAGGGAAAGTACAATCTGGAATGGACTATCTCTTCATTCCGACATTTCTGTCAGTGA





CTTACTGTCCAGCTGCAATCAAATTTCAGGTACCTGGCCCCATGTTGAAAATGAGATCAAGATACACT





CAGAGCTTACAACTTGAACTAATGATAAGAATCCTGTGTAAGCCCGATTCGCCACTTATGAAGGTCCA





TATCCCTGACAAGGAAGGAAGAGGATGTCTTGTATCAGTATGGTTGCATGTATGCAATATCTTCAAAT





CAGGAAACAAGAATGGCAGTGAGTGGCAGGAATACTGGATGAGAAAGTGTGCTAACATGCAACTTGA





AGTGTCGATTGCAGATATGTGGGGACCAACTATCATAATTCATGCCAGAGGTCACATTCCCAAAAGTG





CTAAGTTGTTTTTTGGAAAGGGTGGATGGAGCTGCCATCCACTTCACGAAGTTGTTCCAAGTGTCACTA





AAACACTATGGTCCGTGGGCTGTGAGATTACAAAGGCGAAGGCAATAATACAAGAGAGTAGCATCTC





TCTTCTCGTGGAGACTACTGACATCATAAGTCCAAAAGTCAAAATTTCATCTAAGCATCGCCGCTTTGG





GAAATCAAATTGGGGTCTGTTCAAGAAAACCAAATCACTGCCCAACCTGACGGAGCTGGAATGACTG





ACCCCCAATCGAGACTACACCACCTCAAACTATAGGTGGGTGGTACCTCAGTGATTAATCTCGTAAGC





ACTGATCGTAGGCTACAACACACTAATATTATCCAGATTAGAGAGCTTAATTAGCTCTGTATTAATAAT





AACACTACTATTCCAATAACTGGAATCACCAGCTTGATTTATCTCCAAAATGATTCAAAGAAAACAAA





TCATATTAAGACTATCCTAAGCACGAACCCATATCGTCCTTCAAATCATGGGTACTATAATTCAATTTC





TGGTGGTCTCCTGTCTATTGGCAGGAGCAGGCAGTCTTGATCCAGCAGCCCTCATGCAAATCGGTGTC





ATTCCAACAAATGTCCGGCAACTTATGTATTATACTGAGGCCTCATCAGCATTCATTGTTGTGAAGTTA





ATGCCTACAATTGACTCGCCGATTAGTGGATGTAATATAACATCAATTTCAAGCTATAATGCAACAGT





GACAAAACTCCTACAGCCGATCGGTGAGAATTTGGAGACGATTAGGAACCAGTTGATTCCAACTCGGA





GGAGACGCCGGTTTGCAGGGGTGGTGATTGGATTAGCTGCATTAGGAGTAGCTACTGCCGCACAGGTC





ACTGCCGCAGTAGCACTAGTAAAGGCAAATGAAAATGCTGCGGCTATACTCAATCTCAAAAATGCAAT





CCAAAAAACAAATGCAGCAGTTGCAGATGTGGTCCAGGCCACACAATCACTAGGAACaGCAGTTCAAG





CAGTTCAAGATCACATAAACAGTGTGGTAAGTCCAGCAATTACAGCAGCCAATTGTAAAGCCCAAGAT





GCTATCATTGGCTCAATCCTCAATCTCTATTTGACCGAGTTGACAACTATCTTCCACAATCAAATTACA





AACCCTGCATTGAGTCCTATTACAATTCAAGCTTTAAGGATCCTACTAGGGAGTACCTTGCCGACTGTG





GTCGAAAAATCTTTCAATACCCAGATAAGTGCGGCTGAGCTTCTCTCATCAGGGTTATTGACAGGCCA





GATTGTGGGATTAGATTTGACCTATATGCAGATGGTCATAAAAATTGAGCTGCCAACTTTAACTGTAC





AACCTGCAACCCAGATCATAGATCTGGCCACCATTTCTGCATTCATTAACAATCAAGAAGTCATGGCC





CAATTACCAACACGTGTTATTGTGACTGGCAGCTTGATCCAAGCCTATCCCGCATCGCAATGCACTATT





ACACCCAACACTGTGTACTGTAGGTATAATGATGCCCAAGTACTCTCAGATGATACGATGGCTTGCCT





CCAAGGTAACTTGACAAGATGCACCTTCTCTCCAGTGGTTGGGAGCTTTCTCACTCGATTCGTGCTGTT





CGATGGAATAGTTTATGCAAATTGCAGGTCGATGTTGTGCAAGTGCATGCAGCCTGCTGCTGTGATCCT





ACAGCCGAGTTCATCCCCTGTAACTGTCATTGACATGTACAAATGTGTGAGTCTGCAGCTTGACAATCT





CAGATTCACCATCACTCAATTGGCCAATGTAACCTACAATAGCACCATCAAGCTTGAAACATCCCAGA





TCTTGCCTATTGATCCGTTGGATATATCCCAGAATCTAGCTGCGGTGAATAAGAGTCTAAGTGATGCAC





TACAACACTTAGCACAAAGTGACACATACCTTTCTGCAATCACATCAGCTACGACTACAAGTGTATTA





TCCATAATAGCAATCTGTCTTGGATCGTTAGGTTTAATATTAATAATCTTGCTCAGTGTAGTTGTGTGG





AAGTTATTGACCATTGTCGCTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAATTCAGCATTC





CACCACTCACGATCTGATCTCAGTGAGAAAAATCAACCTGCAACTCTTGGAACAAGATAAGACAGTCA





TCCATTAGTAATTTTTAAGAAAAAAACGATAGGACCGAAACTAGTATTGAAAGAACCGTCTCGGTCAA





TCTAGGTAATCGAGCTGcTACCGTCTCGGAAAGCTCAAATCATGCTGCCTGATCCGGAAGATCCGGAA





AGCAAAAAAGCTACAAGGAGAACAGGAAACCTAATTATCTGCTTCCTATTCATCTTCTTTCCGTTTGTA





AACTTCATTGTTCCAACTCTAAGACACTTGCTGTCCTAACACCTGCTATAGGCTATCCACTGCATCATC





TCTTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCCGGTGCCAACAACACAAT





CCACAATCTACAGTCGACGCGGCCGCCatgttcgtcttcctggtcctgctgcctctggtctcctcacag





tgcgtcaatctgacaactcggactcagctgccacctgcttatactaatagcttcaccagaggcgtgtact





atcctgacaaggtgtttagaagctccgtgctgcactctacacaggatctgtttctgccattctttagcaa





cgtgacctggttccacgccatccacgtgagcggcaccaatgtgataaagcggttcgacaatcccgtgc





tgccttttaacgatggcgtgtacttcgcctctaccgagaagagcaacatcatcagaggctggatctt





tggcaccacactggactccaagacacagtctctgctgatcgtgaacaatgccaccaacgtggtcatc





aaggtgtgcgagttccagttttgtaatgatcccttcctgggcgtgtactatcacaagaacaataagagc





tggatggagtccgagtttagagtgtattctagcgccaacaactgcacatttgagtacgtgagccagcc





tttcctgatggacctggagggcaagcagggcaatttcaagaacctgagggagttcgtgtttaagaatat





cgacggctacttcaaaatctactctaagcacacccccatcaacctggtgcgcgacctgcctcagggctt





cagcgccctggagcccctggtggatctgcctatcggcatcaacatcacccggtttcagacactgctggcc





ctgcacgactcctctagcggatggaccgccggcgctgccgcctactatgtgggctacctccagccccg





gaccttcctgctgaagtacaacgagaatggcaccatcacagacgcagtggattgcgccctggaccccctg





agcgagacaaagtgtacactgaagtcctttaccgtggagaagggcatctatcagacatccaatttcaggg





tgcagccaaccgagtctatcgtgcgctttcctaatatcacaaacctgtgcccatttggcgaggtgttcaa





cgcaacccgcttcgccagcgtgtacgcctggaataggaagcggatcagcaactgcgtggccgactatag





cgtgctgtacaactccgcctctttcagcacctttaagtgctatggcgtgtcccccacaaagctgaatg





acctgtgctttaccaacgtctacgccgattctttcgtgatcaggggcgacgaggtgcgccagatcgccc





ccggccagacaggcaagatcgcagactacaattataagctgccagacgatttcaccggctgcgtgatcg





cctggaacagcaacaatctggattccaaagtgggcggcaactacaattatCAGtaccggctgtttag





aaagagcaatctgaagcccttcgagagggacatctctacagaaatctaccaggccggcagcacccctt





gcaatggcgtggagggctttaactgttattCcccactccagtcctacggcttccagcccacaaacggc





gtgggctatcagccttaccgcgtggtggtgctgagctttgagctgctgcacgccccagcaacagtgtgc





ggccccaagaagtccaccaatctggtgaagaacaagtgcgtgaacttcaacttcaacggcctgaccggca





caggcgtgctgaccgagtccaacaagaagttcctgccatttcagcagttcggcagggacatcgcagatac





cacagacgccgtgcgcgacccacagaccctggagatcctggacatcacaccctgctctttcggcggcgt





gagcgtgatcacacccggcaccaatacaagcaaccaggtggccgtgctgtatcaggGcgtgaattgtacc





gaggtgcccgtggctatccacgccgatcagctgaccccaacatggcgggtgtacagcaccggctccaac





gtcttccagacaagagccggatgcctgatcggagcagagcacgtgaacaattcctatgagtgcgacat





cccaatcggcgccggcatctgtgcctcttaccagacccagacaaactctcccagaagagcccggagcg





tggcctcccagtctatcatcgcctataccatgtccctgggcgccgagaacagcgtggcctactctaac





aatagcatcgccatcccaaccaacttcacaatctctgtgaccacagagatcctgcccgtgtccatga





ccaagacatctgtggactgcacaatgtatatctgtggcgattctaccgagtgcagcaacctgctgctcc





agtacggcagcttttgtacccagctgaatagagccctgacaggcatcgccgtggagcaggataagaac





acacaggaggtgttcgcccaggtgaagcaaatctacaagaccccccctatcaaggactttggcggcttca





atttttcccagatcctgcctgatccatccaagccttctaagcggagctttatcgaggacctgctgttcaa





caaggtgaccctggccgatgccggcttcatcaagcagtatggcgattgcctgggcgacatcgcagccagg





gacctgatctgcgcccagaagtttaatggcctgaAcgtgctgccacccctgctgacagatgagatgatcg





cacagtacacaagcgccctgctggccggcaccatcacatccggatggaccttcggcgcaggagccgccct





ccagatcccctttgccatgcagatggcctataggttcaacggcatcggcgtgacccagaatgtgctgtac





gagaaccagaagctgatcgccaatcagtttaactccgccatcggcaagatccaggacagcctgtcctct





acagccagcgccctgggcaagctccaggatgtggtgaatcagaacgcccaggccctgaataccctggtga





agcagctgagcagcaacttcggcgccatctctagcgtgctgaatgacatcctgagccggctggacaaggt





ggaggcagaggtgcagatcgaccggctgatcaccggccggctccagagcctccagacctatgtgacacag





cagctgatcagggccgccgagatcagggccagcgccaatctggcagcaaccaagatgtccgagtgcgtgc





tgggccagtctaagagagtggacttttgtggcaagggctatcacctgatgtccttccctcagtctgcccc





acacggcgtggtgtttctgcacgtgacctacgtgcccgcccaggagaagaacttcaccacagcccctgc





catctgccacgatggcaaggcccactttccaagggagggcgtgttcgtgtccaacggcacccactggttt





gtgacacagcgcaatttctacgagccccagatcatcaccacagacaacaccttcgtgagcggcaactgtg





acgtggtcatcggcatcgtgaacaataccgtgtatgatccactccagcccgagctggacagctttaagg





aggagctggataagtatttcaagaatcacacctcccctgacgtggatctgggcgacatcagcggcatcaa





tgcctccgtggtgaacatccagaaggagatcgaccgcctgaacgaggtggctaagaatctgaacgagagc





ctgatcgacctccaggagctgggcaagtatgagcagtacatcaagtggccctggtacatctggctgggct





tcatcgccggcctgatcgccatcgtgatggtgaccatcatgctgtgctgtatgacatcctgctgttcttg





cctgaagggctgctgtagctgtggctcctgctgtAAGTTATTGACCATTGTCGTTGCTAATCGAAATAGA





ATGGAGAATTTTGTTTATCATAAATGAtgaACGCGTGCTAGCCTCCTGCCATACTTCCTACTCACATCAT





ATCTATTTTAAAGAAAAAATAGGCCCGAACACTAATCGTGCCGGCAGTGCCACTGCACACACAACACT





ACACATACAATACACTACAATGGTTGCAGAAGATGCCCCTGTTAGGGGCACTTGCCGAGTATTATTTC





GAACAACAACTTTAATTTTTCTATGCACACTATTAGCATTAAGCATCTCTATCCTTTATGAGAGTTTAA





TAACCCAAAAGCAAATCATGAGCCAAGCAGGCTCAACTGGATCTAATTCTAGATTAGGAAGTATCACT





GATCTTCTTAATAATATTCTCTCTGTCGCAAATCAGATTATATATAACTCTGCAGTCGCTCTACCTCTAC





AATTGGACACTCTTGAATCAACACTCCTTACAGCCATTAAGTCTCTTCAAACAAGTGACAAGCTAGAA





CAGAACTGCTCGTGGGGTGCTGCACTGATTAATGATAATAGATACATTAATGGCATCAATCAGTTCTA





TTTCTCAATTGCTGAGGGTCGCAAGCTGACACTTGGCCCACTTCTTAATATACCTAGTTTCATTCCAAC





TGCCACGACACCAGAGGGCTGCACCAGGATCCCATCATTCTCGCTCACCAAGACACACTGGTGTTATA





CACACAATGTTATCCTGAATGGATGCCAGGATCATGTATCCTCAAATCAATTTGTTTCCATGGGAATCA





TTGAACCCACTTCTGCCGGGTTTCCATCCTTTCGAACCCTAAAGACTCTATATCTCAGCGATGGGGTCA





ATCGTAAGAGCTGCTCTATCAGTACAGTTCCGGGGGGTTGTATGATGTACTGTTTCGTCTCTACTCAAC





CAGAGAGGGATGACTACTTTTCTACCGCTCCTCCAGAACAACGAATTATTATAATGTACTATAATGAT





ACAATCGTGGAGCGCATAATTAATCCACCCGGGGTACTAGATGTATGGGCAACATTGAACCCAGGAAC





AGGAAGCGGGGTATATTATTTAGGTTGGGTACTCTTTCCAATATATGGCGGCGTGATTAAAGATACGA





GTTTATGGAATAATCAAGCAAATAAATACTTTATCCCCCAGATGGTTGCTGCTCTCTGCTCACAAAACC





AGGCAACTCAAGTCCAAAATGCTAAGTCATCATACTATAGCAGCTGGTTTGGCAATCGAATGATTCAG





TCTGGGATCCTGGCATGTCCTCTTCAACAGGATCTAACCAATGAGTGTTTAGTTCTGCCCTTTTCTAAT





GATCAGGTGCTTATGGGTGCTGAAGGGAGATTATACATGTATGGTGACTCGGTGTATTACTACCAAAG





AAGCAATAGTTGGTGGCCTATGACCATGCTGTATAAGGTAACCATAACATTCACTAATGGTCAGCCAT





CTGCTATATCAGCTCAGAATGTGCCCACACAGCAGGTCCCTAGACCTGGGACAGGAAGCTGCTCTGCA





ACAAATAGATGTCCCGGTTTTTGCTTGAAAGGAGTGTATGCTGATGCCTGGTTACTGACCAACCCTTCG





TCTACCAGTACATTTGGATCAGAAGCAACCTTCACTGGTTCTTATCTCAACGCAGCAACTCAGCGTATC





AATCCGACGATGTATATCGCGAACAACACACAGATCATAAGCTCACAGCAATTTGGATCAAGCGGTCA





AGAAGCAGCATATGGCCACACAACTTGTTTTAGGGACACAGGCTCTGTTATGGTATACTGTATCTATAT





TATTGAATTGTCCTCATCTCTCTTAGGACAATTTCAGATTGTCCCATTTATCCGTCAGGTGACACTATCC





TAAAGGCAGAAGCCTCCAGGTCTGACCCAGCCAATCAAAGCATTATACCAGACCATGGAATGCATACC





AAACATTATTGACACTAATGACACACAAAATTGGTTTTAAGAAAAACCAAGAGAACAATAGGCCAGA





ATGGCTGGGTCTCGGGAGATATTACTCCCTGAAGTCCATCTCAATTCACCAATTGTAAAGCATAAGCT





ATACTATTACATTCTACTTGGAAACCTCCCAAATGAGATCGACATTGACGATTTAGGTCCATTACATAA





TCAAAATTGGAATCAAATAGCACATGAAGAGTCTAACTTAGCCCAACGCTTGGTAAATGTAAGAAATT





TTCTAATTACCCACATCCCTGATCTTAGAAAGGGCCATTGGCAAGAGTATGTCAATGTAATACTGTGGC





CGCGAATTCTTCCCTTGATCCCGGATTTTAAAATCAATGACCAATTGCCTCTACTCAAAAATTGGGACA





AGTTAGTTAAAGAATCATGTTCAGTAATCAATGCGGGTACTTCCCAGTGCATTCAGAATCTCAGCTATG





GACTGACAGGTCGTGGGAACCTCTTTACACGATCACGTGAACTCTCTGGTGACCGCAGGGATATTGAT





CTTAAGACGGTTGTGGCAGCATGGCATGACTCAGACTGGAAAAGAATAAGTGATTTTTGGATTATGAT





CAAATTCCAGATGAGACAATTAATTGTTAGGCAAACAGATCATAATGATCCTGATTTAATCACGTATA





TCGAAAATAGAGAAGGCATAATCATCATAACCCCTGAACTGGTAGCATTATTTAACACTGAGAATCAT





ACACTAACATACATGACCTTTGAAATTGTACTGATGGTTTCAGATATGTACGAAGGTCGTCACAACATT





TTATCACTATGCACAGTTAGCACTTACCTGAATCCTCTGAAGAAAAGAATAACATATTTATTGAGCCTT





GTAGATAACTTAGCTTTTCAGATAGGTGATGCTGTATATAACATAATTGCTTTGCTAGAATCCTTTGTA





TATGCACAGTTGCAAATGTCAGATCCCATCCCAGAACTCAGAGGACAATTCCATGCATTCGTATGTTCT





GAGATTCTTGATGCACTAAGGGGAACTAATAGTTTCACCCAGGATGAATCAAGAACTGTGACAACCAA





TTTGATATCCCCATTCCAAGATCTGACCCCAGATCTTACGGCTGAATTGCTCTGTATAATGAGGCTTTG





GGGACACCCCATGCTCACCGCCAGTCAAGCTGCGGGAAAGGTACGCGAGTCCATGTGTGCTGGAAAA





GTATTAGACTTTCCCACCATTATGAAAACACTAGCCTTTTTCCATACTATTCTGATCAATGGATACAGG





AGGAAGCATCATGGAGTATGGCCACCCTTAAACTTACCGGGTAATGCTTCAAAGGGTCTCACGGAACT





TATGAATGACAATACTGAGATAAGCTATGAATTCACACTTAAGCATTGGAAGGAAATCTCTCTTATAA





AATTCAAGAAATGTTTTGATGCAGACGCAGGTGAGGAACTCAGTATATTTATGAAAGATAAAGCAATT





AGTGCCCCAAAACAAGATTGGATGAGTGTGTTTAGAAGAAGCCTAATCAAACAGCGCCATCAGCATC





ATCAGGTCCCCCTACCAAATCCATTCAATCGACGGCTATTGCTAAACTTTCTCGGAGATGACAAATTCG





ACCCGAATGTGGAGCTACAGTATGTAACATCAGGTGAGTATCTACATGATGACACGTTTTGTGCATCA





TATTCACTAAAAGAGAAGGAAATTAAACCTGATGGTCGAATTTTTGCAAAGTTGACTAAGAGAATGAG





ATCATGTCAAGTTATAGCAGAATCTCTTTTAGCGAACCATGCTGGGAAGTTAATGAAAGAGAATGGTG





TTGTGATGAATCAGCTATCATTAACAAAATCACTATTAACAATGAGTCAGATTGGAATAATATCCGAG





AAAGCTAGAAAATCGACTCGAGATAACATAAATCAACCTGGTTTCCAGAATATCCAGAGAAATAAAT





CACATCACTCCAAGCAAGTCAATCAGCGAGATCCAAGTGATGACTTTGAATTGGCAGCATCTTTTTTA





ACTACTGATCTCAAAAAATATTGTTTACAATGGAGGTACCAGACAATTATCCCATTTGCTCAATCATTA





AACAGAATGTATGGTTATCCTCATCTCTTTGAGTGGATTCACTTACGGCTAATGCGTAGTACACTTTAC





GTGGGGGATCCCTTCAACCCACCAGCAGATACCAGTCAATTTGATCTAGATAAAGTAATTAATGGAGA





TATCTTCATTGTATCACCCAGAGGTGGAATTGAAGGGCTATGTCAAAAGGCTTGGACAATGATATCTA





TCTCTGTGATAATTCTATCTGCCACAGAGTCTGGCACACGAGTAATGAGTATGGTGCAGGGAGATAAT





CAAGCAATTGCTGTCACCACACGAGTACCAAGGAGCCTGCCGACTCTTGAGAAAAAGACTATTGCTTT





TAGATCTTGTAATCTATTCTTTGAGAGGTTAAAATGTAATAATTTTGGATTAGGTCACCATTTGAAAGA





ACAAGAGACTATCATTAGTTCTCACTTCTTTGTTTATAGCAAGAGAATATTCTATCAGGGGAGGATTCT





AACGCAAGCCTTAAAAAATGCTAGTAAGCTCTGCTTGACAGCTGATGTCCTAGGAGAATGTACCCAAT





CATCATGTTCTAATCTTGCAACTACTGTCATGAGGTTAACTGAGAATGGTGTTGAAAAAGATATCTGTT





TCTACTTGAATATCTATATGACCATCAAACAGCTCTCCTATGATATCATCTTCCCTCAAGTGTCAATTCC





TGGAGATCAGATCACATTAGAATACATAAATAATCCACACCTGGTATCACGATTGGCTCTTCTGCCATC





CCAGCTAGGAGGTCTAAACTACCTGTCATGCAGTAGGCTGTTCAATCGAAACATAGGCGACCCGGTGG





TTTCCGCAGTTGCAGATCTTAAGAGATTAATTAAATCAGGATGTATGGATTACTGGATCCTTTATAACT





TATTAGGGAGAAAACCGGGAAACGGCTCATGGGCTACTTTAGCAGCTGACCCGTACTCAATCAATATA





GAGTATCAATACCCCCCAACTACAGCTCTTAAGAGGCACACCCAACAAGCTCTGATGGAACTCAGTAC





GAATCCAATGTTACGTGGCATATTCTCTGACAATGCACAGGCAGAAGAAAATAATCTTGCTAGATTTC





TCCTGGATAGGGAGGTGATCTTTCCGCGTGTAGCTCACATCATCATTGAGCAAACCAGTGTCGGGAGG





AGAAAACAGATTCAAGGATATTTGGATTCAACTAGATCGATAATGAGTAAATCACTAGAAATTAAGCC





CTTGTCCAATAGGAAGCTTAATGAAATACTGGATTACAACATCAATTACCTAGCTTACAATTTGGCATT





ACTCAAGAATGCTATTGAACCTCCGACTTATTTGAAAGCAATGACTCTTGAAACATGTAGCATCGACA





TTGCAAGGAGCCTCCGGAAGCTCTCCTGGGCCCCACTCTTGGGTGGGAGAAATCTTGAAGGATTAGAG





ACGCCAGATCCCATTGAAATTACTGCAGGAGCATTAATTGTTGGATCGGGCTACTGTGAACAGTGTGC





TGCAGGAGACAATCGATTCACATGGTTTTTCTTGCCATCTGGTATCGAGATAGGAGGGGATCCCCGTG





ATAATCCTCCTATCCGTGTACCGTACATTGGCTCCAGGACTGATGAGAGGAGGGTAGCCTCAATGGCA





TACATCAGGGGTGCCTCGAGTAGCCTAAAAGCAGTTCTTAGACTGGCGGGAGTGTACATCTGGGCATT





CGGAGATACTCTGGAGAATTGGATAGATGCACTGGATTTGTCTCACACTAGAGTTAACATCACACTTG





AACAGCTGCAATCCCTCACCCCACTTCCAACCTCTGCCAATCTAACCCATCGGTTGGATGATGGCACA





ACTACCCTAAAGTTTACTCCTGCGAGCTCTTACACCTTTTCAAGTTTCACTCATATATCAAATGATGAG





CAATACCTGACAATTAATGACAAAACTGCAGATTCAAATATAATCTACCAACAGTTAATGATCACTGG





ACTCGGAATTTTAGAAACATGGAATAATCCCCCAATCAATAGAACATTCGAAGAATCTACCCTACATT





TGCACACTGGTGCATCATGTTGTGTCCGACCTGTGGACTCCTGCATCATCTCAGAAGCATTAACAGTCA





AGCCACATATTACAGTACCGTACAGCAATAAATTTGTATTTGATGAAGACCCGCTATCTGAATATGAG





ACTGCAAAACTGGAATCGTTATCATTTCAAGCCCAATTAGGCAACATTGATGCTGTAGATATGACAGG





TAAATTAACATTATTGTCCCAATTCACTGCAAGGCAGATTATTAATGCAATCACTGGACTCGATGAGTC





TGTCTCTCTTACTAATGATGCCATTGTTGCATCAGACTATGTCTCCAATTGGATTAGTGAATGCATGTA





TACCAAATTAGATGAATTATTTATGTATTGTGGGTGGGAACTACTATTGGAACTATCCTATCAAATGTA





TTATCTGAGGGTAGTTGGGTGGAGTAATATAGTGGATTATTCTTACATGATCTTGAGAAGAATCCCGG





GTGCAGCATTAAACAATCTGGCATCTACATTAAGTCATCCAAAACTTTTCCGACGAGCTATCAACCTA





GATATAGTTGCCCCCTTAAATGCTCCTCATTTTGCATCTCTGGACTACATCAAGATGAGTGTGGATGCA





ATACTCTGGGGCTGTAAAAGAGTCATCAATGTGCTCTCCAATGGAGGGGACTTAGAATTAGTTGTGAC





ATCTGAAGATAGCCTTATTCTCAGTGACCGATCCATGAATCTCATTGCAAGGAAATTAACTTTATTATC





ACTGATTCACCATAATGGTTTGGAACTACCAAAGATTAAGGGGTTCTCTCCTGATGAGAAGTGTTTCGC





TTTGACAGAATTTTTGAGGAAAGTGGTGAACTCAGGGTTGAGTTCAATAGAGAACCTATCAAATTTTA





TGTACAATGTGGAGAACCCACGGCTTGCAGCATTCGCCAGCAACAATTACTACCTGACCAGAAAATTA





TTGAATTCAATACGAGATACTGAGTCGGGTCAAGTAGCAGTCACCTCATATTATGAATCATTAGAATA





TATTGATAGTCTTAAGCTAACCCCACATGTGCCTGGTACCTCATGCATTGAGGATGATAGTCTATGTAC





AAATGATTACATAATCTGGATCATAGAGTCTAATGCAAACTTGGAGAAGTATCCAATTCCAAATAGCC





CTGAGGATGATTCCAATTTCCATAACTTTAAGTTGAATGCTCCATCGCACCATACCTTACGCCCATTAG





GGTTGTCATCAACTGCTTGGTATAAGGGTATAAGCTGTTGCAGGTACCTTGAGCGATTAAAGCTACCA





CAAGGTGATCATTTATATATTGCAGAAGGTAGTGGTGCCAGTATGACAATCATAGAATACCTATTCCC





AGGAAGAAAGATATATTACAATTCTTTATTTAGTAGTGGTGACAATCCCCCACAAAGAAATTATGCAC





CAATGCCTACTCAGTTCATTGAGAGTGTCCCATACAAGCTCTGGCAAGCACACACAGATCAATATCCC





GAGATTTTTGAGGACTTCATCCCTCTATGGAACGGAAATGCCGCCATGACTGACATAGGAATGACAGC





TTGTGTAGAATTCATCATCAATCGAGTCGGCCCAAGGACTTGCAGTTTAGTACATGTAGATTTGGAATC





AAGTGCAAGCTTAAATCAACAATGCCTGTCAAAGCCGATAATTAATGCTATCATCACTGCTACAACTG





TTTTGTGCCCTCATGGGGTGCTTATTCTGAAATATAGTTGGTTGCCATTTACTAGATTTAGTACTTTGAT





CACTTTCTTATGGTGCTACTTTGAGAGAATCACTGTTCTTAGGAGCACATATTCTGGTCCAGCTAATCA





TGAGGTTTATTTAATTTGTATCCTTGCCAACAACTTTGCATTCCAGACTGTCTCGCAGGCAACAGGAAT





GGCGATGACTTTAACCGATCAAGGGTTTACTTTGATATCACCTGAAAGAATAAATCAGTATTGGGATG





GTCACTTGAAGCAAGAACGTATCGTAGCAGAAGCAATTGATAAGGTGGTTCTAGGAGAAGATGCTCTA





TTCAATTCGAGTGATAATGAATTAATTCTCAAATGTGGAGGGACACCAAATGCACGGAATCTTATCGA





TATCGAGCCAGTCGCAACTTTCATAGAATTTGAACAACTGATCTGCACAATGTTGACAACCCACTTGA





AGGAAATAATTGATATAACAAGGTCTGGAACCCAGGATTATGAAAGTTTATTACTCACTCCTTACAAT





TTAGGTCTTCTTGGTAAAATCAGTACGATAGTGAGATTATTAACAGAAAGGATTCTAAATCATACTATC





AGGAATTGGTTGATCCTCCCACCTTCGCTCCGGATGATCGTGAAGCAGGACTTGGAATTCGGCATATTC





AGGATTACTTCCATCCTCAATTCTGATCGGTTCCTGAAGCTTTCTCCAAATAGGAAATACTTGATTACA





CAATTAACTGCAGGCTACATTAGGAAATTGATTGAGGGGGATTGTAATATCGATCTAACCAGACCTAT





CCAAAAACAAATCTGGAAAGCATTAGGTTGTGTAGTCTATTGTCACGATCCAGTAGATCAAAGGGAAT





CAACAGAGTTTATTGATATAAATATTAATGAAGAAATAGACCGCGGGATCGATGGCGAGGAAATCTA





AATATATCAAGAATCAGAATTAGTTTAAGAAAAAAGAAGAGGATTAATCTTGGTTTTCCCCTTGGT.






15. CVL65


The nucleic acid sequence for CVL65 is:










(SEQ ID NO: 74)



ACCAGGGGGAAAACGAAGTGGTGACTCAAATCATCGAAGACCCTCGAGATTACATAGGTCCGGAACC






TATGGCCTTCGTGACCGACCTCGAGTCAGAGTAGTTCAATAAGGACCTATCAAGTTTGGGCAATTTTTC





GTCCCCGACACAAAAATGTCATCCGTGCTTAAAGCATATGAGCGATTCACACTCACTCAAGAACTGCA





AGATCAGAGTGAGGAAGGTACAATCCCACCTACAACACTAAAACCGGTAATCAGGGTATTTATACTAA





CCTCTAATAACCCAGAGCTAAGATCCCGGCTTCTTCTATTCTGCCTACGGATTGTTCTCAGTAATGGTG





CAAGGGATTCCCATCGCTTTGGAGCATTACTTACAATGTTTTCGCTACCATCAGCCACAATGCTCAATC





ATGTCAAATTAGCTGACCAGTCACCAGAAGCTGATATCGAAAGGGTAGAGATCGATGGCTTTGAGGA





GGGATCATTCCGCTTAATCCCCAATGCTCGTTCAGGTATGAGCCGTGGAGAGATCAATGCCTATGCTG





CACTTGCAGAAGATCTACCTGACACACTAAACCATGCAACACCTTTTGTTGATTCCGAAGTCGAGGGA





ACTGCATGGGATGAGATTGAGACTTTCTTAGATATGTGTTACAGTGTCCTAATGCAGGCATGGATAGT





GACTTGCAAGTGCATGACTGCGCCAGACCAACCTGCTGCTTCTATTGAGAAACGCCTGCAAAAATATC





GTCAGCAAGGCAGGATCAACCCGAGATATCTCCTGCAACCGGAGGCTCGAAGAATAATCCAGAATGT





AATCCGAAAGGGAATGGTGGTCAGACATTTCCTCACCTTTGAACTGCAGCTTGCCCGAGCACAAAGCC





TTGTATCAAATAGGTATTATGCTATGGTAGGGGATGTTGGAAAGTATATAGAGAATTGTGGAATGGGA





GGCTTCTTTTTGACACTAAAATATGCATTAGGAACCAGATGGCCCACACTTGCTTTAGCTGCATTTTCA





GGAGAGCTAACAAAGCTAAAGTCCCTCATGGCATTATACCAGACCCTTGGTGAGCAGGCCCGATATTT





GGCCCTATTGGAGTCACCACATTTGATGGATTTTGCTGCAGCAAACTACCCACTGCTATATAGCTATGC





TATGGGAATAGGCTATGTGTTAGATGTCAACATGAGGAACTACGCTTTCTCCAGATCATACATGAATA





AGACATATTTCCAATTGGGAATGGAAACTGCAAGAAAACAACAGGGTGCAGTTGACATGAGGATGGC





AGAAGATCTCGGTCTAACTCAAGCCGAACGCACCGAGATGGCAAATACACTTGCCAAATTGACCACA





GCAAATCGAGGGGCAGACACCAGGGGAGGAGTCAACCCGTTCTCATCTATCACTGGGACAACTCAGG





TGCCCGCTGCAGCAACAGGTGACACATTCGAGAGTTACATGGCAGCGGATCGACTGAGGCAGAGATA





TGCTGATGCAGGCACCCACGATGATGAGATGCCACCATTGGAAGAGGAGGAAGAGGACGACACATCT





GCAGGTCCACGCACTGGACTAACTCTTGAACAAGTGGCCTTGGACATCCAGAACGCAGCAGTTGGAGC





TCCCATCCATACAGATGACCTGAATGCCGCACTGGGTGATCTTGACATCTAGACAATTCAGATCCCAA





TCTTAAATCGACACACCTAATTGACCAGTTAGATGGAACTACAGTGGATTCCATAAGGTTCCTGCCTAC





CATCGGCTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCCGATGCCAATAACA





CAATCCACAATCTACAATGGATCCCACTGATCTGAGCTTCTCCCCAGATGAGATCAATAAGCTCATAG





AGACAGGCCTGAATACTGTGGAGTATTTTACTTCCCAACAAGTCACAGGAACATCCTCTCTTGGAAAG





AATACAATACCACCAGGGGTCACAGGACTACTAACCAATGCTGCAGAGGCAAAGATCCAAGAGTCAA





CCAACCATCAGAAGGGTTCAGTTGGTGGGGGCGCAAAACCAAAGAAACCGCGACCAAAAATTGCCAT





TGTGCCAGCAGATGACAAAACGGTGCCCGGAAAGCCGATCCCAAACCCTCTATTAGGTCTGGACTCCA





CCCCGAGCACCCAAACTGTGCTTGATCTAAGTGGGAAAACATTACCATCAGGATCCTATAAGGGGGTT





AAACTTGCGAAATTTGGAAAAGAAAATCTGATGACACGGTTCATCGAGGAACCCAGAGAGAATCCTA





TCGCAACCAATTCCCCCATCGATTTTAAGAGGGGCAGGGATACCGGCGGGTTCCATAGAAGGGAGTAC





TCAATCGGATGGGTGGGAGATGAAGTCAAGGTCACTGAGTGGTGCAATCCATCCTGTTCTCCAATCAC





CGCTGCAGCAAGGCGATTTGAATGCACTTGTCACCAGTGTCCAGTCACTTGCTCTGAATGTGAACGAG





ATACTTAATACAGTGAGAAATTTGGACTCTCGGATGAATCAACTGGAGACAAAAGTAGATCGCATTCT





CTCATCTCAGTCTCTAATCCAGACCATCAAGAATGACATAGTTGGACTTAAAGCAGGGATGGCTACTT





TAGAAGGAATGATTACAACTGTGAAAATCATGGACCCGGGAGTTCCCAGTAATGTTACTGTGGAAGAT





GTACGCAAGAAACTAAGTAACCATGCTGTTGTTGTGCCAGAATCATTCAATGATAGTTTCTTGACTCAA





TCTGAAGATGTAATTTCACTTGATGAGTTGGCTCGACCAACTGCAACAAGTGTTAAGAAGATTGTCAG





GAAGGTTCCTCCTCAGAAGGATCTGACTGGATTGAAGATCACACTAGAGCAATTGGCAAAGGATTGCA





TCAGCAAACCGAAGATGAGGGAAGAGTATCTCCTCAAAATCAACCAGGCTTCCAGTGAGGCTCAGCT





AATTGACCTCAAGAAAGCAATCATCCGCAGTGCAATTTGATCAAGAAACACCCAATTACACTACACTG





GTATGACACTGTACTAACCCTGAGGGTTTTAGAAAAAACGATTAACGATAAATAAGCCCGAACACTAC





ACACCACCCGAGGCAGCCATGCCATCCATCAGCATCCCCGCAGACCCCACCAATCCACGTCAATCAAT





AAAAGCGTTCCCAATTGTGATCAACCGTGATGGGGGTGAGAAAGGTCGCTTGGTTAAACAACTACGCA





CAACCTACTTGAATGACCTAGATACTCATGAGCCACTGGTGACATTCGTAAATACTTATGGATTCATCT





ACGAACAGGATCGGGGAAATACCATTGTCGGAGAGGATCAACATGGGAAGAAAAGAGAGGCTGTGA





CTGCTGCAATGGTTACCCTTGGATGTGGGCCTAATCTACCATCATTAGGGAATGTCCTGGGACAACTG





AGTGAATTCCAGGTCATTGTTAGGAAGACATCCAGCAAAGCGGAAGAGATGGTCTTTGAAATTGTTAA





GTATCCGAGAATATTTCGGGGTCATACATTAATCCAGAAAGGACTAGTCTGTGTCTCCGCAGAAAAAT





TTGTTAAGTCACCAGGGAAAGTACAATCTGGAATGGACTATCTCTTCATTCCGACATTTCTGTCAGTGA





CTTACTGTCCAGCTGCAATCAAATTTCAGGTACCTGGCCCCATGTTGAAAATGAGATCAAGATACACT





CAGAGCTTACAACTTGAACTAATGATAAGAATCCTGTGTAAGCCCGATTCGCCACTTATGAAGGTCCA





TATCCCTGACAAGGAAGGAAGAGGATGTCTTGTATCAGTATGGTTGCATGTATGCAATATCTTCAAAT





CAGGAAACAAGAATGGCAGTGAGTGGCAGGAATACTGGATGAGAAAGTGTGCTAACATGCAACTTGA





AGTGTCGATTGCAGATATGTGGGGACCAACTATCATAATTCATGCCAGAGGTCACATTCCCAAAAGTG





CTAAGTTGTTTTTTGGAAAGGGTGGATGGAGCTGCCATCCACTTCACGAAGTTGTTCCAAGTGTCACTA





AAACACTATGGTCCGTGGGCTGTGAGATTACAAAGGCGAAGGCAATAATACAAGAGAGTAGCATCTC





TCTTCTCGTGGAGACTACTGACATCATAAGTCCAAAAGTCAAAATTTCATCTAAGCATCGCCGCTTTGG





GAAATCAAATTGGGGTCTGTTCAAGAAAACCAAATCACTGCCCAACCTGACGGAGCTGGAATGACTG





ACCCCCAATCGAGACTACACCACCTCAAACTATAGGTGGGTGGTACCTCAGTGATTAATCTCGTAAGC





ACTGATCGTAGGCTACAACACACTAATATTATCCAGATTAGAGAGCTTAATTAGCTCTGTATTAATAAT





AACACTACTATTCCAATAACTGGAATCACCAGCTTGATTTATCTCCAAAATGATTCAAAGAAAACAAA





TCATATTAAGACTATCCTAAGCACGAACCCATATCGTCCTTCAAATCATGGGTACTATAATTCAATTTC





TGGTGGTCTCCTGTCTATTGGCAGGAGCAGGCAGTCTTGATCCAGCAGCCCTCATGCAAATCGGTGTC





ATTCCAACAAATGTCCGGCAACTTATGTATTATACTGAGGCCTCATCAGCATTCATTGTTGTGAAGTTA





ATGCCTACAATTGACTCGCCGATTAGTGGATGTAATATAACATCAATTTCAAGCTATAATGCAACAGT





GACAAAACTCCTACAGCCGATCGGTGAGAATTTGGAGACGATTAGGAACCAGTTGATTCCAACTCGGA





GGAGACGCCGGTTTGCAGGGGTGGTGATTGGATTAGCTGCATTAGGAGTAGCTACTGCCGCACAGGTC





ACTGCCGCAGTAGCACTAGTAAAGGCAAATGAAAATGCTGCGGCTATACTCAATCTCAAAAATGCAAT





CCAAAAAACAAATGCAGCAGTTGCAGATGTGGTCCAGGCCACACAATCACTAGGAACaGCAGTTCAAG





CAGTTCAAGATCACATAAACAGTGTGGTAAGTCCAGCAATTACAGCAGCCAATTGTAAAGCCCAAGAT





GCTATCATTGGCTCAATCCTCAATCTCTATTTGACCGAGTTGACAACTATCTTCCACAATCAAATTACA





AACCCTGCATTGAGTCCTATTACAATTCAAGCTTTAAGGATCCTACTAGGGAGTACCTTGCCGACTGTG





GTCGAAAAATCTTTCAATACCCAGATAAGTGCGGCTGAGCTTCTCTCATCAGGGTTATTGACAGGCCA





GATTGTGGGATTAGATTTGACCTATATGCAGATGGTCATAAAAATTGAGCTGCCAACTTTAACTGTAC





AACCTGCAACCCAGATCATAGATCTGGCCACCATTTCTGCATTCATTAACAATCAAGAAGTCATGGCC





CAATTACCAACACGTGTTATTGTGACTGGCAGCTTGATCCAAGCCTATCCCGCATCGCAATGCACTATT





ACACCCAACACTGTGTACTGTAGGTATAATGATGCCCAAGTACTCTCAGATGATACGATGGCTTGCCT





CCAAGGTAACTTGACAAGATGCACCTTCTCTCCAGTGGTTGGGAGCTTTCTCACTCGATTCGTGCTGTT





CGATGGAATAGTTTATGCAAATTGCAGGTCGATGTTGTGCAAGTGCATGCAGCCTGCTGCTGTGATCCT





ACAGCCGAGTTCATCCCCTGTAACTGTCATTGACATGTACAAATGTGTGAGTCTGCAGCTTGACAATCT





CAGATTCACCATCACTCAATTGGCCAATGTAACCTACAATAGCACCATCAAGCTTGAAACATCCCAGA





TCTTGCCTATTGATCCGTTGGATATATCCCAGAATCTAGCTGCGGTGAATAAGAGTCTAAGTGATGCAC





TACAACACTTAGCACAAAGTGACACATACCTTTCTGCAATCACATCAGCTACGACTACAAGTGTATTA





TCCATAATAGCAATCTGTCTTGGATCGTTAGGTTTAATATTAATAATCTTGCTCAGTGTAGTTGTGTGG





AAGTTATTGACCATTGTCGCTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAATTCAGCATTC





CACCACTCACGATCTGATCTCAGTGAGAAAAATCAACCTGCAACTCTTGGAACAAGATAAGACAGTCA





TCCATTAGTAATTTTTAAGAAAAAAACGATAGGACCGAAACTAGTATTGAAAGAACCGTCTCGGTCAA





TCTAGGTAATCGAGCTGcTACCGTCTCGGAAAGCTCAAATCGCGCGCCACCatgtcagataacggacca






cagaaccagaggaacgcacccaggattactttcggaggaccaagcgatagcaccgggagcaaccagaatg







gagagcggagcggagcaagatccaagcagagacggccccagggcctgccaaacaataccgcatcctgg







ttcaccgccctgacacagcacggcaaggaggacctgaagtttccaaggggacagggagtgcctatcaa







caccaatagctcccctgacgatcagatcggctactataggagggcaacaaggagaatcaggggaggcgac







ggcaagatgaaggatctgagcccacgctggtacttctactatctgggaaccggacctgaggcaggcct







gccatatggcgccaacaaggacggaatcatctgggtggcaaccgagggcgccctgaacacaccaaagga







tcacatcggcacaagaaatcccgccaacaatgcagcaatcgtgctgcagctgccacagggaaccacact







gcccaagggcttttacgcagagggctctcggggaggcagccaggcatctagcagatcctctagccggagc







agaaactcctctaggaattccaccccaggaagctccaggggcacatcccctgcccgcatggcaggaa







acggaggcgacgccgccctggccctgctgctgctggatcgcctgaatcagctggagtccaagatgtctgg







caagggacagcagcagcagggacagaccgtgacaaagaagtccgccgccgaggcctctaagaagccaagg







cagaagcgcaccgccacaaaggcctacaacgtgacccaggccttcggcaggcgcggaccagagca







gacacagggcaattttggcgaccaggagctgatcaggcagggaaccgattataagcactggcctca







gatcgcccagttcgccccatctgccagcgccttctttggcatgtctagaatcggcatggaggtgac







ccccagcggcacatggctgacctacacaggcgccatcaagctggacgataaggaccctaacttcaagg







atcaggtcatcctgctgaacaagcacatcgacgcctataagacctttccccctacagagcccaagaa







ggacaagaagaagaaggccgatgagacacaggccctgcctcagaggcagaagaagcagcagaccgtga







cactgctgccagccgccgatctggacgatttctccaaacagctgcagcagagcatgtccagtgc







cgactccacccaggcttgaGCTAGCCTCCTGCCATACTTCCTACTCACATCATA






TCTATTTTAAAGAAAAAATAGGCCCGAACACTAATCGTGCCGGCAGTGCCACTGCACACACAA





CACTACACATACAATACACTACAATGGTTGCAGAAGATGCCCCTGTTAGGGGCACTTGCCGAGTATTA





TTTCGAACAACAACTTTAATTTTTCTATGCACACTATTAGCATTAAGCATCTCTATCCTTTATGAGAGTT





TAATAACCCAAAAGCAAATCATGAGCCAAGCAGGCTCAACTGGATCTAATTCTAGATTAGGAAGTATC





ACTGATCTTCTTAATAATATTCTCTCTGTCGCAAATCAGATTATATATAACTCTGCAGTCGCTCTACCTC





TACAATTGGACACTCTTGAATCAACACTCCTTACAGCCATTAAGTCTCTTCAAACAAGTGACAAGCTA





GAACAGAACTGCTCGTGGGGTGCTGCACTGATTAATGATAATAGATACATTAATGGCATCAATCAGTT





CTATTTCTCAATTGCTGAGGGTCGCAAGCTGACACTTGGCCCACTTCTTAATATACCTAGTTTCATTCC





AACTGCCACGACACCAGAGGGCTGCACCAGGATCCCATCATTCTCGCTCACCAAGACACACTGGTGTT





ATACACACAATGTTATCCTGAATGGATGCCAGGATCATGTATCCTCAAATCAATTTGTTTCCATGGGAA





TCATTGAACCCACTTCTGCCGGGTTTCCATCCTTTCGAACCCTAAAGACTCTATATCTCAGCGATGGGG





TCAATCGTAAGAGCTGCTCTATCAGTACAGTTCCGGGGGGTTGTATGATGTACTGTTTCGTCTCTACTC





AACCAGAGAGGGATGACTACTTTTCTACCGCTCCTCCAGAACAACGAATTATTATAATGTACTATAAT





GATACAATCGTGGAGCGCATAATTAATCCACCCGGGGTACTAGATGTATGGGCAACATTGAACCCAGG





AACAGGAAGCGGGGTATATTATTTAGGTTGGGTACTCTTTCCAATATATGGCGGCGTGATTAAAGATA





CGAGTTTATGGAATAATCAAGCAAATAAATACTTTATCCCCCAGATGGTTGCTGCTCTCTGCTCACAAA





ACCAGGCAACTCAAGTCCAAAATGCTAAGTCATCATACTATAGCAGCTGGTTTGGCAATCGAATGATT





CAGTCTGGGATCCTGGCATGTCCTCTTCAACAGGATCTAACCAATGAGTGTTTAGTTCTGCCCTTTTCT





AATGATCAGGTGCTTATGGGTGCTGAAGGGAGATTATACATGTATGGTGACTCGGTGTATTACTACCA





AAGAAGCAATAGTTGGTGGCCTATGACCATGCTGTATAAGGTAACCATAACATTCACTAATGGTCAGC





CATCTGCTATATCAGCTCAGAATGTGCCCACACAGCAGGTCCCTAGACCTGGGACAGGAAGCTGCTCT





GCAACAAATAGATGTCCCGGTTTTTGCTTGAAAGGAGTGTATGCTGATGCCTGGTTACTGACCAACCCT





TCGTCTACCAGTACATTTGGATCAGAAGCAACCTTCACTGGTTCTTATCTCAACGCAGCAACTCAGCGT





ATCAATCCGACGATGTATATCGCGAACAACACACAGATCATAAGCTCACAGCAATTTGGATCAAGCGG





TCAAGAAGCAGCATATGGCCACACAACTTGTTTTAGGGACACAGGCTCTGTTATGGTATACTGTATCT





ATATTATTGAATTGTCCTCATCTCTCTTAGGACAATTTCAGATTGTCCCATTTATCCGTCAGGTGACACT





ATCCTAAACCTGCTATAGGCTATCCACTGCATCATCTCTTTTTAAGAAAAAAATAGGCCCGGACGGGTT





AGCAACAAGCGACTGCCGGTGCCAACAACACAATCCACAATCTACAGTCGACGCGGCCGCCACCatgttc





gtcttcctggtcctgctgcctctggtctcctcacagtgcgtcaatctgagaactcggactcagctgccac





ctgcttatactaatagcttcaccagaggcgtgtactatcctgacaaggtgtttagaagctccgtgctgc





actctacacaggatctgtttctgccattctttagcaacgtgacctggttccacgccatccacgtgagc





ggcaccaatggcacaaagcggttcgacaatcccgtgctgccttttaacgatggcgtgtacttcgcctct





accgagaagagcaacatcatcagaggctggatctttggcaccacactggactccaagacacagtctc





tgctgatcgtgaacaatgccaccaacgtggtcatcaaggtgtgcgagttccagttttgtaatgatccct





tcctgggcgtgtactatcacaagaacaataagagctggatggagtccggcgtgtattctagcgccaa





caactgcacatttgagtacgtgagccagcctttcctgatggacctggagggcaagcagggcaatttcaa





gaacctgagggagttcgtgtttaagaatatcgacggctacttcaaaatctactctaagcacacccccatc





aacctggtgcgcgacctgcctcagggcttcagcgccctggagcccctggtggatctgcctatcggcatca





acatcacccggtttcagacactgctggccctgcacagaagctacctgacacccggcgactcctctagc





ggatggaccgccggcgctgccgcctactatgtgggctacctccagccccggaccttcctgctgaagtac





aacgagaatggcaccatcacagacgcagtggattgcgccctggaccccctgagcgagacaaagtgtaca





ctgaagtcctttaccgtggagaagggcatctatcagacatccaatttcagggtgcagccaaccgagt





ctatcgtgcgctttcctaatatcacaaacctgtgcccatttggcgaggtgttcaacgcaacccgcttc





gccagcgtgtacgcctggaataggaagcggatcagcaactgcgtggccgactatagcgtgctgtacaa





ctccgcctctttcagcacctttaagtgctatggcgtgtcccccacaaagctgaatgacctgtgctttac





caacgtctacgccgattctttcgtgatcaggggcgacgaggtgcgccagatcgcccccggccagacaggc





aagatcgcagactacaattataagctgccagacgatttcaccggctgcgtgatcgcctggaacagcaaca





atctggattccaaagtgggcggcaactacaattatagataccggctgtttagaaagagcaatctgaagcc





cttcgagagggacatctctacagaaatctaccaggccggcagcaagccttgcaatggcgtggagggc





tttaactgttatttcccactccagtcctacggcttccagcccacaaacggcgtgggctatcagcctta





ccgcgtggtggtgctgagctttgagctgctgcacgccccagcaacagtgtgcggccccaagaagtcca





ccaatctggtgaagaacaagtgcgtgaacttcaacttcaacggcctgaccggcacaggcgtgctgac





cgagtccaacaagaagttcctgccatttcagcagttcggcagggacatcgcagataccacagacgccgt





gcgcgacccacagaccctggagatcctggacatcacaccctgctctttcggcggcgtgagcgtgatcac





acccggcaccaatacaagcaaccaggtggccgtgctgtatcagggcgtgaattgtaccgaggtgc





ccgtggctatccacgccgatcagctgaccccaacatggcgggtgtacagcaccggctccaacgtct





tccagacaagagccggatgcctgatcggagcagagcacgtgaacaattcctatgagtgcgacatcc





caatcggcgccggcatctgtgcctcttaccagacccagacaaactctagaagaagagcccggagcgtg





gcctcccagtctatcatcgcctataccatgtccctgggcgccgagaacagcgtggcctactctaaca





atagcatcgccatcccaaccaacttcacaatctctgtgaccacagagatcctgcccgtgtccatgacca





agacatctgtggactgcacaatgtatatctgtggcgattctaccgagtgcagcaacctgctgctccag





tacggcagcttttgtacccagctgaatagagccctgacaggcatcgccgtggagcaggataagaacaca





caggaggtgttcgcccaggtgaagcaaatctacaagaccccccctatcaaggactttggcggcttcaa





tttttcccagatcctgcctgatccatccaagccttctaagcggagctttatcgaggacctgctgttc





aacaaggtgaccctggccgatgccggcttcatcaagcagtatggcgattgcctgggcgacatcgc





agccagggacctgatctgcgcccagaagtttaatggcctgaccgtgctgccacccctgctgacagatgag





atgatcgcacagtacacaagcgccctgctggccggcaccatcacatccggatggaccttcggcgcagg





agccgccctccagatcccctttgccatgcagatggcctataggttcaacggcatcggcgtgaccca





gaatgtgctgtacgagaaccagaagctgatcgccaatcagtttaactccgccatcggcaagatccag





gacagcctgtcctctacagccagcgccctgggcaagctccagaacgtggtgaatcagaacgcccaggcc





ctgaataccctggtgaagcagctgagcagcaacttcggcgccatctctagcgtgctgaatgacatcct





gagccggctggacaaggtggaggcagaggtgcagatcgaccggctgatcaccggccggctccagagc





ctccagacctatgtgacacagcagctgatcagggccgccgagatcagggccagcgccaatctggcag





caaccaagatgtccgagtgcgtgctgggccagtctaagagagtggacttttgtggcaagggctatc





acctgatgtccttccctcagtctgccccacacggcgtggtgtttctgcacgtgacctacgtgcccgcc





caggagaagaacttcaccacagcccctgccatctgccacgatggcaaggcccactttccaagggaggg





cgtgttcgtgtccaacggcacccactggtttgtgacacagcgcaatttctacgagccccagatcatcac





cacagacaacaccttcgtgagcggcaactgtgacgtggtcatcggcatcgtgaacaataccgtgtat





gatccactccagcccgagctggacagctttaaggaggagctggataagtatttcaagaatcacacctc





ccctgacgtggatctgggcgacatcagcggcatcaatgcctccgtggtgaacatccagaaggagatcg





accgcctgaacgaggtggctaagaatctgaacgagagcctgatcgacctccaggagctgggcaagta





tgagcagtacatcaagtggccctggtacatctggctgggcttcatcgccggcctgatcgccatcgtga





tggtgaccatcatgctgtgctgtatgacatcctgctgttcttgcctgaagggctgctgtagctgtggc





tcctgctgtAAGTTATTGACCATTGTCGTTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAA





ATGAATTCGTACGAGGCAGAAGCCTCCAGGTCTGACCCAGCCAATCAAAGCATTATACCAGACCATGG





AATGCATACCAAACATTATTGACACTAATGACACACAAAATTGGTTTTAAGAAAAACCAAGAGAACA





ATAGGCCAGAATGGCTGGGTCTCGGGAGATATTACTCCCTGAAGTCCATCTCAATTCACCAATTGTAA





AGCATAAGCTATACTATTACATTCTACTTGGAAACCTCCCAAATGAGATCGACATTGACGATTTAGGTC





CATTACATAATCAAAATTGGAATCAAATAGCACATGAAGAGTCTAACTTAGCCCAACGCTTGGTAAAT





GTAAGAAATTTTCTAATTACCCACATCCCTGATCTTAGAAAGGGCCATTGGCAAGAGTATGTCAATGT





AATACTGTGGCCGCGAATTCTTCCCTTGATCCCGGATTTTAAAATCAATGACCAATTGCCTCTACTCAA





AAATTGGGACAAGTTAGTTAAAGAATCATGTTCAGTAATCAATGCGGGTACTTCCCAGTGCATTCAGA





ATCTCAGCTATGGACTGACAGGTCGTGGGAACCTCTTTACACGATCACGTGAACTCTCTGGTGACCGC





AGGGATATTGATCTTAAGACGGTTGTGGCAGCATGGCATGACTCAGACTGGAAAAGAATAAGTGATTT





TTGGATTATGATCAAATTCCAGATGAGACAATTAATTGTTAGGCAAACAGATCATAATGATCCTGATTT





AATCACGTATATCGAAAATAGAGAAGGCATAATCATCATAACCCCTGAACTGGTAGCATTATTTAACA





CTGAGAATCATACACTAACATACATGACCTTTGAAATTGTACTGATGGTTTCAGATATGTACGAAGGT





CGTCACAACATTTTATCACTATGCACAGTTAGCACTTACCTGAATCCTCTGAAGAAAAGAATAACATA





TTTATTGAGCCTTGTAGATAACTTAGCTTTTCAGATAGGTGATGCTGTATATAACATAATTGCTTTGCT





AGAATCCTTTGTATATGCACAGTTGCAAATGTCAGATCCCATCCCAGAACTCAGAGGACAATTCCATG





CATTCGTATGTTCTGAGATTCTTGATGCACTAAGGGGAACTAATAGTTTCACCCAGGATGAATCAAGA





ACTGTGACAACCAATTTGATATCCCCATTCCAAGATCTGACCCCAGATCTTACGGCTGAATTGCTCTGT





ATAATGAGGCTTTGGGGACACCCCATGCTCACCGCCAGTCAAGCTGCGGGAAAGGTACGCGAGTCCAT





GTGTGCTGGAAAAGTATTAGACTTTCCCACCATTATGAAAACACTAGCCTTTTTCCATACTATTCTGAT





CAATGGATACAGGAGGAAGCATCATGGAGTATGGCCACCCTTAAACTTACCGGGTAATGCTTCAAAGG





GTCTCACGGAACTTATGAATGACAATACTGAGATAAGCTATGAATTCACACTTAAGCATTGGAAGGAA





ATCTCTCTTATAAAATTCAAGAAATGTTTTGATGCAGACGCAGGTGAGGAACTCAGTATATTTATGAA





AGATAAAGCAATTAGTGCCCCAAAACAAGATTGGATGAGTGTGTTTAGAAGAAGCCTAATCAAACAG





CGCCATCAGCATCATCAGGTCCCCCTACCAAATCCATTCAATCGACGGCTATTGCTAAACTTTCTCGGA





GATGACAAATTCGACCCGAATGTGGAGCTACAGTATGTAACATCAGGTGAGTATCTACATGATGACAC





GTTTTGTGCATCATATTCACTAAAAGAGAAGGAAATTAAACCTGATGGTCGAATTTTTGCAAAGTTGA





CTAAGAGAATGAGATCATGTCAAGTTATAGCAGAATCTCTTTTAGCGAACCATGCTGGGAAGTTAATG





AAAGAGAATGGTGTTGTGATGAATCAGCTATCATTAACAAAATCACTATTAACAATGAGTCAGATTGG





AATAATATCCGAGAAAGCTAGAAAATCGACTCGAGATAACATAAATCAACCTGGTTTCCAGAATATCC





AGAGAAATAAATCACATCACTCCAAGCAAGTCAATCAGCGAGATCCAAGTGATGACTTTGAATTGGCA





GCATCTTTTTTAACTACTGATCTCAAAAAATATTGTTTACAATGGAGGTACCAGACAATTATCCCATTT





GCTCAATCATTAAACAGAATGTATGGTTATCCTCATCTCTTTGAGTGGATTCACTTACGGCTAATGCGT





AGTACACTTTACGTGGGGGATCCCTTCAACCCACCAGCAGATACCAGTCAATTTGATCTAGATAAAGT





AATTAATGGAGATATCTTCATTGTATCACCCAGAGGTGGAATTGAAGGGCTATGTCAAAAGGCTTGGA





CAATGATATCTATCTCTGTGATAATTCTATCTGCCACAGAGTCTGGCACACGAGTAATGAGTATGGTGC





AGGGAGATAATCAAGCAATTGCTGTCACCACACGAGTACCAAGGAGCCTGCCGACTCTTGAGAAAAA





GACTATTGCTTTTAGATCTTGTAATCTATTCTTTGAGAGGTTAAAATGTAATAATTTTGGATTAGGTCA





CCATTTGAAAGAACAAGAGACTATCATTAGTTCTCACTTCTTTGTTTATAGCAAGAGAATATTCTATCA





GGGGAGGATTCTAACGCAAGCCTTAAAAAATGCTAGTAAGCTCTGCTTGACAGCTGATGTCCTAGGAG





AATGTACCCAATCATCATGTTCTAATCTTGCAACTACTGTCATGAGGTTAACTGAGAATGGTGTTGAAA





AAGATATCTGTTTCTACTTGAATATCTATATGACCATCAAACAGCTCTCCTATGATATCATCTTCCCTCA





AGTGTCAATTCCTGGAGATCAGATCACATTAGAATACATAAATAATCCACACCTGGTATCACGATTGG





CTCTTCTGCCATCCCAGCTAGGAGGTCTAAACTACCTGTCATGCAGTAGGCTGTTCAATCGAAACATAG





GCGACCCGGTGGTTTCCGCAGTTGCAGATCTTAAGAGATTAATTAAATCAGGATGTATGGATTACTGG





ATCCTTTATAACTTATTAGGGAGAAAACCGGGAAACGGCTCATGGGCTACTTTAGCAGCTGACCCGTA





CTCAATCAATATAGAGTATCAATACCCCCCAACTACAGCTCTTAAGAGGCACACCCAACAAGCTCTGA





TGGAACTCAGTACGAATCCAATGTTACGTGGCATATTCTCTGACAATGCACAGGCAGAAGAAAATAAT





CTTGCTAGATTTCTCCTGGATAGGGAGGTGATCTTTCCGCGTGTAGCTCACATCATCATTGAGCAAACC





AGTGTCGGGAGGAGAAAACAGATTCAAGGATATTTGGATTCAACTAGATCGATAATGAGTAAATCACT





AGAAATTAAGCCCTTGTCCAATAGGAAGCTTAATGAAATACTGGATTACAACATCAATTACCTAGCTT





ACAATTTGGCATTACTCAAGAATGCTATTGAACCTCCGACTTATTTGAAAGCAATGACTCTTGAAACAT





GTAGCATCGACATTGCAAGGAGCCTCCGGAAGCTCTCCTGGGCCCCACTCTTGGGTGGGAGAAATCTT





GAAGGATTAGAGACGCCAGATCCCATTGAAATTACTGCAGGAGCATTAATTGTTGGATCGGGCTACTG





TGAACAGTGTGCTGCAGGAGACAATCGATTCACATGGTTTTTCTTGCCATCTGGTATCGAGATAGGAG





GGGATCCCCGTGATAATCCTCCTATCCGTGTACCGTACATTGGCTCCAGGACTGATGAGAGGAGGGTA





GCCTCAATGGCATACATCAGGGGTGCCTCGAGTAGCCTAAAAGCAGTTCTTAGACTGGCGGGAGTGTA





CATCTGGGCATTCGGAGATACTCTGGAGAATTGGATAGATGCACTGGATTTGTCTCACACTAGAGTTA





ACATCACACTTGAACAGCTGCAATCCCTCACCCCACTTCCAACCTCTGCCAATCTAACCCATCGGTTGG





ATGATGGCACAACTACCCTAAAGTTTACTCCTGCGAGCTCTTACACCTTTTCAAGTTTCACTCATATAT





CAAATGATGAGCAATACCTGACAATTAATGACAAAACTGCAGATTCAAATATAATCTACCAACAGTTA





ATGATCACTGGACTCGGAATTTTAGAAACATGGAATAATCCCCCAATCAATAGAACATTCGAAGAATC





TACCCTACATTTGCACACTGGTGCATCATGTTGTGTCCGACCTGTGGACTCCTGCATCATCTCAGAAGC





ATTAACAGTCAAGCCACATATTACAGTACCGTACAGCAATAAATTTGTATTTGATGAAGACCCGCTAT





CTGAATATGAGACTGCAAAACTGGAATCGTTATCATTTCAAGCCCAATTAGGCAACATTGATGCTGTA





GATATGACAGGTAAATTAACATTATTGTCCCAATTCACTGCAAGGCAGATTATTAATGCAATCACTGG





ACTCGATGAGTCTGTCTCTCTTACTAATGATGCCATTGTTGCATCAGACTATGTCTCCAATTGGATTAG





TGAATGCATGTATACCAAATTAGATGAATTATTTATGTATTGTGGGTGGGAACTACTATTGGAACTATC





CTATCAAATGTATTATCTGAGGGTAGTTGGGTGGAGTAATATAGTGGATTATTCTTACATGATCTTGAG





AAGAATCCCGGGTGCAGCATTAAACAATCTGGCATCTACATTAAGTCATCCAAAACTTTTCCGACGAG





CTATCAACCTAGATATAGTTGCCCCCTTAAATGCTCCTCATTTTGCATCTCTGGACTACATCAAGATGA





GTGTGGATGCAATACTCTGGGGCTGTAAAAGAGTCATCAATGTGCTCTCCAATGGAGGGGACTTAGAA





TTAGTTGTGACATCTGAAGATAGCCTTATTCTCAGTGACCGATCCATGAATCTCATTGCAAGGAAATTA





ACTTTATTATCACTGATTCACCATAATGGTTTGGAACTACCAAAGATTAAGGGGTTCTCTCCTGATGAG





AAGTGTTTCGCTTTGACAGAATTTTTGAGGAAAGTGGTGAACTCAGGGTTGAGTTCAATAGAGAACCT





ATCAAATTTTATGTACAATGTGGAGAACCCACGGCTTGCAGCATTCGCCAGCAACAATTACTACCTGA





CCAGAAAATTATTGAATTCAATACGAGATACTGAGTCGGGTCAAGTAGCAGTCACCTCATATTATGAA





TCATTAGAATATATTGATAGTCTTAAGCTAACCCCACATGTGCCTGGTACCTCATGCATTGAGGATGAT





AGTCTATGTACAAATGATTACATAATCTGGATCATAGAGTCTAATGCAAACTTGGAGAAGTATCCAAT





TCCAAATAGCCCTGAGGATGATTCCAATTTCCATAACTTTAAGTTGAATGCTCCATCGCACCATACCTT





ACGCCCATTAGGGTTGTCATCAACTGCTTGGTATAAGGGTATAAGCTGTTGCAGGTACCTTGAGCGATT





AAAGCTACCACAAGGTGATCATTTATATATTGCAGAAGGTAGTGGTGCCAGTATGACAATCATAGAAT





ACCTATTCCCAGGAAGAAAGATATATTACAATTCTTTATTTAGTAGTGGTGACAATCCCCCACAAAGA





AATTATGCACCAATGCCTACTCAGTTCATTGAGAGTGTCCCATACAAGCTCTGGCAAGCACACACAGA





TCAATATCCCGAGATTTTTGAGGACTTCATCCCTCTATGGAACGGAAATGCCGCCATGACTGACATAG





GAATGACAGCTTGTGTAGAATTCATCATCAATCGAGTCGGCCCAAGGACTTGCAGTTTAGTACATGTA





GATTTGGAATCAAGTGCAAGCTTAAATCAACAATGCCTGTCAAAGCCGATAATTAATGCTATCATCAC





TGCTACAACTGTTTTGTGCCCTCATGGGGTGCTTATTCTGAAATATAGTTGGTTGCCATTTACTAGATTT





AGTACTTTGATCACTTTCTTATGGTGCTACTTTGAGAGAATCACTGTTCTTAGGAGCACATATTCTGGT





CCAGCTAATCATGAGGTTTATTTAATTTGTATCCTTGCCAACAACTTTGCATTCCAGACTGTCTCGCAG





GCAACAGGAATGGCGATGACTTTAACCGATCAAGGGTTTACTTTGATATCACCTGAAAGAATAAATCA





GTATTGGGATGGTCACTTGAAGCAAGAACGTATCGTAGCAGAAGCAATTGATAAGGTGGTTCTAGGAG





AAGATGCTCTATTCAATTCGAGTGATAATGAATTAATTCTCAAATGTGGAGGGACACCAAATGCACGG





AATCTTATCGATATCGAGCCAGTCGCAACTTTCATAGAATTTGAACAACTGATCTGCACAATGTTGACA





ACCCACTTGAAGGAAATAATTGATATAACAAGGTCTGGAACCCAGGATTATGAAAGTTTATTACTCAC





TCCTTACAATTTAGGTCTTCTTGGTAAAATCAGTACGATAGTGAGATTATTAACAGAAAGGATTCTAAA





TCATACTATCAGGAATTGGTTGATCCTCCCACCTTCGCTCCGGATGATCGTGAAGCAGGACTTGGAATT





CGGCATATTCAGGATTACTTCCATCCTCAATTCTGATCGGTTCCTGAAGCTTTCTCCAAATAGGAAATA





CTTGATTACACAATTAACTGCAGGCTACATTAGGAAATTGATTGAGGGGGATTGTAATATCGATCTAA





CCAGACCTATCCAAAAACAAATCTGGAAAGCATTAGGTTGTGTAGTCTATTGTCACGATCCAGTAGAT





CAAAGGGAATCAACAGAGTTTATTGATATAAATATTAATGAAGAAATAGACCGCGGGATCGATGGCG





AGGAAATCTAAATATATCAAGAATCAGAATTAGTTTAAGAAAAAAGAAGAGGATTAATCTTGGTTTTC





CCCTTGGT.






16. CVL67


The nucleic acid sequence for CVL67 is:









(SEQ ID NO: 75)


ACCAGGGGGAAAACGAAGTGGTGACTCAAATCATCGAAGACCCTCGAGA





TTACATAGGTCCGGAACCTATGGCCTTCGTGACCGACCTCGAGTCAGAG





TAGTTCAATAAGGACCTATCAAGTTTGGGCAATTTTTCGTCCCCGACAC





AAAAATGTCATCCGTGCTTAAAGCATATGAGCGATTCACACTCACTCAA





GAACTGCAAGATCAGAGTGAGGAAGGTACAATCCCACCTACAACACTAA





AACCGGTAATCAGGGTATTTATACTAACCTCTAATAACCCAGAGCTAAG





ATCCCGGCTTCTTCTATTCTGCCTACGGATTGTTCTCAGTAATGGTGCA





AGGGATTCCCATCGCTTTGGAGCATTACTTACAATGTTTTCGCTACCAT





CAGCCACAATGCTCAATCATGTCAAATTAGCTGACCAGTCACCAGAAGC





TGATATCGAAAGGGTAGAGATCGATGGCTTTGAGGAGGGATCATTCCGC





TTAATCCCCAATGCTCGTTCAGGTATGAGCCGTGGAGAGATCAATGCCT





ATGCTGCACTTGCAGAAGATCTACCTGACACACTAAACCATGCAACACC





TTTTGTTGATTCCGAAGTCGAGGGAACTGCATGGGATGAGATTGAGACT





TTCTTAGATATGTGTTACAGTGTCCTAATGCAGGCATGGATAGTGACTT





GCAAGTGCATGACTGCGCCAGACCAACCTGCTGCTTCTATTGAGAAACG





CCTGCAAAAATATCGTCAGCAAGGCAGGATCAACCCGAGATATCTCCTG





CAACCGGAGGCTCGAAGAATAATCCAGAATGTAATCCGAAAGGGAATGG





TGGTCAGACATTTCCTCACCTTTGAACTGCAGCTTGCCCGAGCACAAAG





CCTTGTATCAAATAGGTATTATGCTATGGTAGGGGATGTTGGAAAGTAT





ATAGAGAATTGTGGAATGGGAGGCTTCTTTTTGACACTAAAATATGCAT





TAGGAACCAGATGGCCCACACTTGCTTTAGCTGCATTTTCAGGAGAGCT





AACAAAGCTAAAGTCCCTCATGGCATTATACCAGACCCTTGGTGAGCAG





GCCCGATATTTGGCCCTATTGGAGTCACCACATTTGATGGATTTTGCTG





CAGCAAACTACCCACTGCTATATAGCTATGCTATGGGAATAGGCTATGT





GTTAGATGTCAACATGAGGAACTACGCTTTCTCCAGATCATACATGAAT





AAGACATATTTCCAATTGGGAATGGAAACTGCAAGAAAACAACAGGGTG





CAGTTGACATGAGGATGGCAGAAGATCTCGGTCTAACTCAAGCCGAACG





CACCGAGATGGCAAATACACTTGCCAAATTGACCACAGCAAATCGAGGG





GCAGACACCAGGGGAGGAGTCAACCCGTTCTCATCTATCACTGGGACAA





CTCAGGTGCCCGCTGCAGCAACAGGTGACACATTCGAGAGTTACATGGC





AGCGGATCGACTGAGGCAGAGATATGCTGATGCAGGCACCCACGATGAT





GAGATGCCACCATTGGAAGAGGAGGAAGAGGACGACACATCTGCAGGTC





CACGCACTGGACTAACTCTTGAACAAGTGGCCTTGGACATCCAGAACGC





AGCAGTTGGAGCTCCCATCCATACAGATGACCTGAATGCCGCACTGGGT





GATCTTGACATCTAGACAATTCAGATCCCAATCTTAAATCGACACACCT





AATTGACCAGTTAGATGGAACTACAGTGGATTCCATAAGGTTCCTGCCT





ACCATCGGCTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGC





GACTGCCGATGCCAATAACACAATCCACAATCTACAATGGATCCCACTG





ATCTGAGCTTCTCCCCAGATGAGATCAATAAGCTCATAGAGACAGGCCT





GAATACTGTGGAGTATTTTACTTCCCAACAAGTCACAGGAACATCCTCT





CTTGGAAAGAATACAATACCACCAGGGGTCACAGGACTACTAACCAATG





CTGCAGAGGCAAAGATCCAAGAGTCAACCAACCATCAGAAGGGTTCAGT





TGGTGGGGGCGCAAAACCAAAGAAACCGCGACCAAAAATTGCCATTGTG





CCAGCAGATGACAAAACGGTGCCCGGAAAGCCGATCCCAAACCCTCTAT





TAGGTCTGGACTCCACCCCGAGCACCCAAACTGTGCTTGATCTAAGTGG





GAAAACATTACCATCAGGATCCTATAAGGGGGTTAAACTTGCGAAATTT





GGAAAAGAAAATCTGATGACACGGTTCATCGAGGAACCCAGAGAGAATC





CTATCGCAACCAATTCCCCCATCGATTTTAAGAGGGGCAGGGATACCGG





CGGGTTCCATAGAAGGGAGTACTCAATCGGATGGGTGGGAGATGAAGTC





AAGGTCACTGAGTGGTGCAATCCATCCTGTTCTCCAATCACCGCTGCAG





CAAGGCGATTTGAATGCACTTGTCACCAGTGTCCAGTCACTTGCTCTGA





ATGTGAACGAGATACTTAATACAGTGAGAAATTTGGACTCTCGGATGAA





TCAACTGGAGACAAAAGTAGATCGCATTCTCTCATCTCAGTCTCTAATC





CAGACCATCAAGAATGACATAGTTGGACTTAAAGCAGGGATGGCTACTT





TAGAAGGAATGATTACAACTGTGAAAATCATGGACCCGGGAGTTCCCAG





TAATGTTACTGTGGAAGATGTACGCAAGAAACTAAGTAACCATGCTGTT





GTTGTGCCAGAATCATTCAATGATAGTTTCTTGACTCAATCTGAAGATG





TAATTTCACTTGATGAGTTGGCTCGACCAACTGCAACAAGTGTTAAGAA





GATTGTCAGGAAGGTTCCTCCTCAGAAGGATCTGACTGGATTGAAGATC





ACACTAGAGCAATTGGCAAAGGATTGCATCAGCAAACCGAAGATGAGGG





AAGAGTATCTCCTCAAAATCAACCAGGCTTCCAGTGAGGCTCAGCTAAT





TGACCTCAAGAAAGCAATCATCCGCAGTGCAATTTGATCAAGAAACACC





CAATTACACTACACTGGTATGACACTGTACTAACCCTGAGGGTTTTAGA





AAAAACGATTAACGATAAATAAGCCCGAACACTACACACCACCCGAGGC





AGCCATGCCATCCATCAGCATCCCCGCAGACCCCACCAATCCACGTCAA





TCAATAAAAGCGTTCCCAATTGTGATCAACCGTGATGGGGGTGAGAAAG





GTCGCTTGGTTAAACAACTACGCACAACCTACTTGAATGACCTAGATAC





TCATGAGCCACTGGTGACATTCGTAAATACTTATGGATTCATCTACGAA





CAGGATCGGGGAAATACCATTGTCGGAGAGGATCAACATGGGAAGAAAA





GAGAGGCTGTGACTGCTGCAATGGTTACCCTTGGATGTGGGCCTAATCT





ACCATCATTAGGGAATGTCCTGGGACAACTGAGTGAATTCCAGGTCATT





GTTAGGAAGACATCCAGCAAAGCGGAAGAGATGGTCTTTGAAATTGTTA





AGTATCCGAGAATATTTCGGGGTCATACATTAATCCAGAAAGGACTAGT





CTGTGTCTCCGCAGAAAAATTTGTTAAGTCACCAGGGAAAGTACAATCT





GGAATGGACTATCTCTTCATTCCGACATTTCTGTCAGTGACTTACTGTC





CAGCTGCAATCAAATTTCAGGTACCTGGCCCCATGTTGAAAATGAGATC





AAGATACACTCAGAGCTTACAACTTGAACTAATGATAAGAATCCTGTGT





AAGCCCGATTCGCCACTTATGAAGGTCCATATCCCTGACAAGGAAGGAA





GAGGATGTCTTGTATCAGTATGGTTGCATGTATGCAATATCTTCAAATC





AGGAAACAAGAATGGCAGTGAGTGGCAGGAATACTGGATGAGAAAGTGT





GCTAACATGCAACTTGAAGTGTCGATTGCAGATATGTGGGGACCAACTA





TCATAATTCATGCCAGAGGTCACATTCCCAAAAGTGCTAAGTTGTTTTT





TGGAAAGGGTGGATGGAGCTGCCATCCACTTCACGAAGTTGTTCCAAGT





GTCACTAAAACACTATGGTCCGTGGGCTGTGAGATTACAAAGGCGAAGG





CAATAATACAAGAGAGTAGCATCTCTCTTCTCGTGGAGACTACTGACAT





CATAAGTCCAAAAGTCAAAATTTCATCTAAGCATCGCCGCTTTGGGAAA





TCAAATTGGGGTCTGTTCAAGAAAACCAAATCACTGCCCAACCTGACGG





AGCTGGAATGACTGACCCCCAATCGAGACTACACCACCTCAAACTATAG





GTGGGTGGTACCTCAGTGATTAATCTCGTAAGCACTGATCGTAGGCTAC





AACACACTAATATTATCCAGATTAGAGAGCTTAATTAGCTCTGTATTAA





TAATAACACTACTATTCCAATAACTGGAATCACCAGCTTGATTTATCTC





CAAAATGATTCAAAGAAAACAAATCATATTAAGACTATCCTAAGCACGA





ACCCATATCGTCCTTCAAATCATGGGTACTATAATTCAATTTCTGGTGG





TCTCCTGTCTATTGGCAGGAGCAGGCAGTCTTGATCCAGCAGCCCTCAT





GCAAATCGGTGTCATTCCAACAAATGTCCGGCAACTTATGTATTATACT





GAGGCCTCATCAGCATTCATTGTTGTGAAGTTAATGCCTACAATTGACT





CGCCGATTAGTGGATGTAATATAACATCAATTTCAAGCTATAATGCAAC





AGTGACAAAACTCCTACAGCCGATCGGTGAGAATTTGGAGACGATTAGG





AACCAGTTGATTCCAACTCGGAGGAGACGCCGGTTTGCAGGGGTGGTGA





TTGGATTAGCTGCATTAGGAGTAGCTACTGCCGCACAGGTCACTGCCGC





AGTAGCACTAGTAAAGGCAAATGAAAATGCTGCGGCTATACTCAATCTC





AAAAATGCAATCCAAAAAACAAATGCAGCAGTTGCAGATGTGGTCCAGG





CCACACAATCACTAGGAACaGCAGTTCAAGCAGTTCAAGATCACATAAA





CAGTGTGGTAAGTCCAGCAATTACAGCAGCCAATTGTAAAGCCCAAGAT





GCTATCATTGGCTCAATCCTCAATCTCTATTTGACCGAGTTGACAACTA





TCTTCCACAATCAAATTACAAACCCTGCATTGAGTCCTATTACAATTCA





AGCTTTAAGGATCCTACTAGGGAGTACCTTGCCGACTGTGGTCGAAAAA





TCTTTCAATACCCAGATAAGTGCGGCTGAGCTTCTCTCATCAGGGTTAT





TGACAGGCCAGATTGTGGGATTAGATTTGACCTATATGCAGATGGTCAT





AAAAATTGAGCTGCCAACTTTAACTGTACAACCTGCAACCCAGATCATA





GATCTGGCCACCATTTCTGCATTCATTAACAATCAAGAAGTCATGGCCC





AATTACCAACACGTGTTATTGTGACTGGCAGCTTGATCCAAGCCTATCC





CGCATCGCAATGCACTATTACACCCAACACTGTGTACTGTAGGTATAAT





GATGCCCAAGTACTCTCAGATGATACGATGGCTTGCCTCCAAGGTAACT





TGACAAGATGCACCTTCTCTCCAGTGGTTGGGAGCTTTCTCACTCGATT





CGTGCTGTTCGATGGAATAGTTTATGCAAATTGCAGGTCGATGTTGTGC





AAGTGCATGCAGCCTGCTGCTGTGATCCTACAGCCGAGTTCATCCCCTG





TAACTGTCATTGACATGTACAAATGTGTGAGTCTGCAGCTTGACAATCT





CAGATTCACCATCACTCAATTGGCCAATGTAACCTACAATAGCACCATC





AAGCTTGAAACATCCCAGATCTTGCCTATTGATCCGTTGGATATATCCC





AGAATCTAGCTGCGGTGAATAAGAGTCTAAGTGATGCACTACAACACTT





AGCACAAAGTGACACATACCTTTCTGCAATCACATCAGCTACGACTACA





AGTGTATTATCCATAATAGCAATCTGTCTTGGATCGTTAGGTTTAATAT





TAATAATCTTGCTCAGTGTAGTTGTGTGGAAGTTATTGACCATTGTCGC





TGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAATTCAGCATTC





CACCACTCACGATCTGATCTCAGTGAGAAAAATCAACCTGCAACTCTTG





GAACAAGATAAGACAGTCATCCATTAGTAATTTTTAAGAAAAAAACGAT





AGGACCGAAACTAGTATTGAAAGAACCGTCTCGGTCAATCTAGGTAATC





GAGCTGcTACCGTCTCGGAAAGCTCAAATCATGCTGCCTGATCCGGAAG





ATCCGGAAAGCAAAAAAGCTACAAGGAGAACAGGAAACCTAATTATCTG





CTTCCTATTCATCTTCTTTCCGTTTGTAAACTTCATTGTTCCAACTCTA





AGACACTTGCTGTCCTAACACCTGCTATAGGCTATCCACTGCATCATCT





CTTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCC





GGTGCCAACAACACAATCCACAATCTACAGTCGACGCGGCCGCCatgtt





cgtcttcctggtcctgctgcctctggtctcctcacagtgcgtcaatctg





acaactcggactcagctgccacctgcttatactaatagcttcaccagag





gcgtgtactatcctgacaaggtgtttagaagctccgtgctgcactctac





acaggatctgtttctgccattctttagcaacgtgacctggttccacgcc





atccacgtgagcggcaccaatggcacaaagcggttcgacaatcccgtgc





tgccttttaacgatggcgtgtacttcgcctctatcgagaagagcaacat





catcagaggctggatctttggcaccacactggactccaagacacagtct





ctgctgatcgtgaacaatgccaccaacgtggtcatcaaggtgtgcgagt





tccagttttgtaatgatcccttcctgggcgtgacatccaaccacaagaa





caataagagctggatggagtccgagtttagagtgtattctagcgccaac





aactgcacatttgagtacgtgagccagcctttcctgatggacctggagg





gcaagcagggcaatttcaagaacctgagggagttcgtgtttaagaatat





cgacggctacttcaaaatctactctaagcacacccccatcaacctggtg





cgcgacctgcctcagggcttcagcgccctggagcccctggtggatctgc





ctatcggcatcaacatcacccggtttcagacactgctggccctgcacag





aagctacctgacacccggcgactcctctagcggatggaccgccggcgct





gccgcctactatgtgggctacctccagccccggaccttcctgctgaagt





acaacgagaatggcaccatcacagacgcagtggattgcgccctggaccc





cctgagcgagacaaagtgtacactgaagtcctttaccgtggagaagggc





atctatcagacatccaatttcagggtgcagccaaccgagtctatcgtgc





gctttcctaatatcacaaacctgtgcccatttggcgaggtgttcaacgc





aaccaagttcgccagcgtgtacgcctggaataggaagcggatcagcaac





tgcgtggccgactatagcgtgctgtacaactccgcctctttcagcacct





ttaagtgctatggcgtgtcccccacaaagctgaatgacctgtgctttac





caacgtctacgccgattctttcgtgatcaggggcgacgaggtgcgccag





atcgcccccggccagacaggcaagatcgcagactacaattataagctgc





cagacgatttcaccggctgcgtgatcgcctggaacagcaacaatctgga





ttccaaagtgggcggcaactacaattatctgtaccggctgtttagaaag





agcaatctgaagcccttcgagagggacatctctacagaaatctaccagg





ccggcagcaccccttgcaatggcgtgaagggcttcaactgctacttccc





tctgcaatcctacggctttcagcccacatacggcgtgggctaccagcca





taccgggtcgtggtgctgagcttcgagctgctgcacgcccctgccacag





tgtgcggccctaagaagagcaccaatctggtaaagaacaagtgcgtcaa





cttcaatttcaacggcctgaccgggaccggagtgctgaccgaaagcaac





aagaaattcctgccgttccagcagttcggcagagatatcgccgacacca





ccgatgccgtgcgggacccccagacacttgaaatcctggacatcacccc





ttgcagttttggcggcgtgtccgtgatcacacctggaacaaacaccagc





aaccaggtggccgtgctgtaccagggcgtcaactgcaccgaggtccccg





tggccatccacgccgatcagctgacacctacatggcgggtgtactctac





cggcagcaacgtgttccaaaccagagccggctgcctgatcggcgctgag





cacgtgaacaacagctacgagtgcgacattcctatcggtgctggcatct





gcgcctcttaccagacacagacaaacagccacagaagagcccggagcgt





ggcctcccagtctatcatcgcctataccatgtccctgggcgccgagaac





agcgtggcctactctaacaatagcatcgccatcccaaccaacttcacaa





tctctgtgaccacagagatcctgcccgtgtccatgaccaagacatctgt





ggactgcacaatgtatatctgtggcgattctaccgagtgcagcaacctg





ctgctccagtacggcagcttttgtacccagctgaatagagccctgacag





gcatcgccgtggagcaggataagaacacacaggaggtgttcgcccaggt





gaagcaaatctacaagaccccccctatcaaggactttggcggcttcaat





ttttcccagatcctgcctgatccatccaagccttctaagcggagcttta





tcgaggacctgctgttcaacaaggtgaccctggccgatgccggcttcat





caagcagtatggcgattgcctgggcgacatcgcagccagggacctgatc





tgcgcccagaagtttaatggcctgaccgtgctgccacccctgctgacag





atgagatgatcgcacagtacacaagcgccctgctggccggcaccatcac





atccggatggaccttcggcgcaggagccgccctccagatcccctttgcc





atgcagatggcctataggttcaacggcatcggcgtgacccagaatgtgc





tgtacgagaaccagaagctgatcgccaatcagtttaactccgccatcgg





caagatccaggacagcctgtcctctacagccagcgccctgggcaagctc





cagaatgtggtgaatcagaacgcccaggccctgaataccctggtgaagc





agctgagcagcaacttcggcgccatctctagcgtgctgaatgacatcct





gagccggctggacaaggtggaggcagaggtgcagatcgaccggctgatc





accggccggctccagagcctccagacctatgtgacacagcagctgatca





gggccgccgagatcagggccagcgccaatctggcagcaaccaagatgtc





cgagtgcgtgctgggccagtctaagagagtggacttttgtggcaagggc





tatcacctgatgtccttccctcagtctgccccacacggcgtggtgtttc





tgcacgtgacctacgtgcccgcccaggagaagaacttcaccacagcccc





tgccatctgccacgatggcaaggcccactttccaagggagggcgtgttc





gtgtccaacggcacccactggtttgtgacacagcgcaatttctacgagc





cccagatcatcaccacagacaacaccttcgtgagcggcaactgtgacgt





ggtcatcggcatcgtgaacaataccgtgtatgatccactccagcccgag





ctggacagctttaaggaggagctggataagtatttcaagaatcacacct





cccctgacgtggatctgggcgacatcagcggcatcaatgcctccgtggt





gaacatccagaaggagatcgaccgcctgaacgaggtggctaagaatctg





aacgagagcctgatcgacctccaggagctgggcaagtatgagcagtaca





tcaagtggccctggtacatctggctgggcttcatcgccggcctgatcgc





catcgtgatggtgaccatcatgctgtgctgtatgacatcctgctgttct





tgcctgaagggctgctgtagctgtggctcctgctgtAAGTTATTGACCA





TTGTCGTTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAAATG





ATGAACGCGTGCTAGCCTCCTGCCATACTTCCTACTCACATCATATCTA





TTTTAAAGAAAAAATAGGCCCGAACACTAATCGTGCCGGCAGTGCCACT





GCACACACAACACTACACATACAATACACTACAATGGTTGCAGAAGATG





CCCCTGTTAGGGGCACTTGCCGAGTATTATTTCGAACAACAACTTTAAT





TTTTCTATGCACACTATTAGCATTAAGCATCTCTATCCTTTATGAGAGT





TTAATAACCCAAAAGCAAATCATGAGCCAAGCAGGCTCAACTGGATCTA





ATTCTAGATTAGGAAGTATCACTGATCTTCTTAATAATATTCTCTCTGT





CGCAAATCAGATTATATATAACTCTGCAGTCGCTCTACCTCTACAATTG





GACACTCTTGAATCAACACTCCTTACAGCCATTAAGTCTCTTCAAACAA





GTGACAAGCTAGAACAGAACTGCTCGTGGGGTGCTGCACTGATTAATGA





TAATAGATACATTAATGGCATCAATCAGTTCTATTTCTCAATTGCTGAG





GGTCGCAAGCTGACACTTGGCCCACTTCTTAATATACCTAGTTTCATTC





CAACTGCCACGACACCAGAGGGCTGCACCAGGATCCCATCATTCTCGCT





CACCAAGACACACTGGTGTTATACACACAATGTTATCCTGAATGGATGC





CAGGATCATGTATCCTCAAATCAATTTGTTTCCATGGGAATCATTGAAC





CCACTTCTGCCGGGTTTCCATCCTTTCGAACCCTAAAGACTCTATATCT





CAGCGATGGGGTCAATCGTAAGAGCTGCTCTATCAGTACAGTTCCGGGG





GGTTGTATGATGTACTGTTTCGTCTCTACTCAACCAGAGAGGGATGACT





ACTTTTCTACCGCTCCTCCAGAACAACGAATTATTATAATGTACTATAA





TGATACAATCGTGGAGCGCATAATTAATCCACCCGGGGTACTAGATGTA





TGGGCAACATTGAACCCAGGAACAGGAAGCGGGGTATATTATTTAGGTT





GGGTACTCTTTCCAATATATGGCGGCGTGATTAAAGATACGAGTTTATG





GAATAATCAAGCAAATAAATACTTTATCCCCCAGATGGTTGCTGCTCTC





TGCTCACAAAACCAGGCAACTCAAGTCCAAAATGCTAAGTCATCATACT





ATAGCAGCTGGTTTGGCAATCGAATGATTCAGTCTGGGATCCTGGCATG





TCCTCTTCAACAGGATCTAACCAATGAGTGTTTAGTTCTGCCCTTTTCT





AATGATCAGGTGCTTATGGGTGCTGAAGGGAGATTATACATGTATGGTG





ACTCGGTGTATTACTACCAAAGAAGCAATAGTTGGTGGCCTATGACCAT





GCTGTATAAGGTAACCATAACATTCACTAATGGTCAGCCATCTGCTATA





TCAGCTCAGAATGTGCCCACACAGCAGGTCCCTAGACCTGGGACAGGAA





GCTGCTCTGCAACAAATAGATGTCCCGGTTTTTGCTTGAAAGGAGTGTA





TGCTGATGCCTGGTTACTGACCAACCCTTCGTCTACCAGTACATTTGGA





TCAGAAGCAACCTTCACTGGTTCTTATCTCAACGCAGCAACTCAGCGTA





TCAATCCGACGATGTATATCGCGAACAACACACAGATCATAAGCTCACA





GCAATTTGGATCAAGCGGTCAAGAAGCAGCATATGGCCACACAACTTGT





TTTAGGGACACAGGCTCTGTTATGGTATACTGTATCTATATTATTGAAT





TGTCCTCATCTCTCTTAGGACAATTTCAGATTGTCCCATTTATCCGTCA





GGTGACACTATCCTAAAGGCAGAAGCCTCCAGGTCTGACCCAGCCAATC





AAAGCATTATACCAGACCATGGAATGCATACCAAACATTATTGACACTA





ATGACACACAAAATTGGTTTTAAGAAAAACCAAGAGAACAATAGGCCAG





AATGGCTGGGTCTCGGGAGATATTACTCCCTGAAGTCCATCTCAATTCA





CCAATTGTAAAGCATAAGCTATACTATTACATTCTACTTGGAAACCTCC





CAAATGAGATCGACATTGACGATTTAGGTCCATTACATAATCAAAATTG





GAATCAAATAGCACATGAAGAGTCTAACTTAGCCCAACGCTTGGTAAAT





GTAAGAAATTTTCTAATTACCCACATCCCTGATCTTAGAAAGGGCCATT





GGCAAGAGTATGTCAATGTAATACTGTGGCCGCGAATTCTTCCCTTGAT





CCCGGATTTTAAAATCAATGACCAATTGCCTCTACTCAAAAATTGGGAC





AAGTTAGTTAAAGAATCATGTTCAGTAATCAATGCGGGTACTTCCCAGT





GCATTCAGAATCTCAGCTATGGACTGACAGGTCGTGGGAACCTCTTTAC





ACGATCACGTGAACTCTCTGGTGACCGCAGGGATATTGATCTTAAGACG





GTTGTGGCAGCATGGCATGACTCAGACTGGAAAAGAATAAGTGATTTTT





GGATTATGATCAAATTCCAGATGAGACAATTAATTGTTAGGCAAACAGA





TCATAATGATCCTGATTTAATCACGTATATCGAAAATAGAGAAGGCATA





ATCATCATAACCCCTGAACTGGTAGCATTATTTAACACTGAGAATCATA





CACTAACATACATGACCTTTGAAATTGTACTGATGGTTTCAGATATGTA





CGAAGGTCGTCACAACATTTTATCACTATGCACAGTTAGCACTTACCTG





AATCCTCTGAAGAAAAGAATAACATATTTATTGAGCCTTGTAGATAACT





TAGCTTTTCAGATAGGTGATGCTGTATATAACATAATTGCTTTGCTAGA





ATCCTTTGTATATGCACAGTTGCAAATGTCAGATCCCATCCCAGAACTC





AGAGGACAATTCCATGCATTCGTATGTTCTGAGATTCTTGATGCACTAA





GGGGAACTAATAGTTTCACCCAGGATGAATCAAGAACTGTGACAACCAA





TTTGATATCCCCATTCCAAGATCTGACCCCAGATCTTACGGCTGAATTG





CTCTGTATAATGAGGCTTTGGGGACACCCCATGCTCACCGCCAGTCAAG





CTGCGGGAAAGGTACGCGAGTCCATGTGTGCTGGAAAAGTATTAGACTT





TCCCACCATTATGAAAACACTAGCCTTTTTCCATACTATTCTGATCAAT





GGATACAGGAGGAAGCATCATGGAGTATGGCCACCCTTAAACTTACCGG





GTAATGCTTCAAAGGGTCTCACGGAACTTATGAATGACAATACTGAGAT





AAGCTATGAATTCACACTTAAGCATTGGAAGGAAATCTCTCTTATAAAA





TTCAAGAAATGTTTTGATGCAGACGCAGGTGAGGAACTCAGTATATTTA





TGAAAGATAAAGCAATTAGTGCCCCAAAACAAGATTGGATGAGTGTGTT





TAGAAGAAGCCTAATCAAACAGCGCCATCAGCATCATCAGGTCCCCCTA





CCAAATCCATTCAATCGACGGCTATTGCTAAACTTTCTCGGAGATGACA





AATTCGACCCGAATGTGGAGCTACAGTATGTAACATCAGGTGAGTATCT





ACATGATGACACGTTTTGTGCATCATATTCACTAAAAGAGAAGGAAATT





AAACCTGATGGTCGAATTTTTGCAAAGTTGACTAAGAGAATGAGATCAT





GTCAAGTTATAGCAGAATCTCTTTTAGCGAACCATGCTGGGAAGTTAAT





GAAAGAGAATGGTGTTGTGATGAATCAGCTATCATTAACAAAATCACTA





TTAACAATGAGTCAGATTGGAATAATATCCGAGAAAGCTAGAAAATCGA





CTCGAGATAACATAAATCAACCTGGTTTCCAGAATATCCAGAGAAATAA





ATCACATCACTCCAAGCAAGTCAATCAGCGAGATCCAAGTGATGACTTT





GAATTGGCAGCATCTTTTTTAACTACTGATCTCAAAAAATATTGTTTAC





AATGGAGGTACCAGACAATTATCCCATTTGCTCAATCATTAAACAGAAT





GTATGGTTATCCTCATCTCTTTGAGTGGATTCACTTACGGCTAATGCGT





AGTACACTTTACGTGGGGGATCCCTTCAACCCACCAGCAGATACCAGTC





AATTTGATCTAGATAAAGTAATTAATGGAGATATCTTCATTGTATCACC





CAGAGGTGGAATTGAAGGGCTATGTCAAAAGGCTTGGACAATGATATCT





ATCTCTGTGATAATTCTATCTGCCACAGAGTCTGGCACACGAGTAATGA





GTATGGTGCAGGGAGATAATCAAGCAATTGCTGTCACCACACGAGTACC





AAGGAGCCTGCCGACTCTTGAGAAAAAGACTATTGCTTTTAGATCTTGT





AATCTATTCTTTGAGAGGTTAAAATGTAATAATTTTGGATTAGGTCACC





ATTTGAAAGAACAAGAGACTATCATTAGTTCTCACTTCTTTGTTTATAG





CAAGAGAATATTCTATCAGGGGAGGATTCTAACGCAAGCCTTAAAAAAT





GCTAGTAAGCTCTGCTTGACAGCTGATGTCCTAGGAGAATGTACCCAAT





CATCATGTTCTAATCTTGCAACTACTGTCATGAGGTTAACTGAGAATGG





TGTTGAAAAAGATATCTGTTTCTACTTGAATATCTATATGACCATCAAA





CAGCTCTCCTATGATATCATCTTCCCTCAAGTGTCAATTCCTGGAGATC





AGATCACATTAGAATACATAAATAATCCACACCTGGTATCACGATTGGC





TCTTCTGCCATCCCAGCTAGGAGGTCTAAACTACCTGTCATGCAGTAGG





CTGTTCAATCGAAACATAGGCGACCCGGTGGTTTCCGCAGTTGCAGATC





TTAAGAGATTAATTAAATCAGGATGTATGGATTACTGGATCCTTTATAA





CTTATTAGGGAGAAAACCGGGAAACGGCTCATGGGCTACTTTAGCAGCT





GACCCGTACTCAATCAATATAGAGTATCAATACCCCCCAACTACAGCTC





TTAAGAGGCACACCCAACAAGCTCTGATGGAACTCAGTACGAATCCAAT





GTTACGTGGCATATTCTCTGACAATGCACAGGCAGAAGAAAATAATCTT





GCTAGATTTCTCCTGGATAGGGAGGTGATCTTTCCGCGTGTAGCTCACA





TCATCATTGAGCAAACCAGTGTCGGGAGGAGAAAACAGATTCAAGGATA





TTTGGATTCAACTAGATCGATAATGAGTAAATCACTAGAAATTAAGCCC





TTGTCCAATAGGAAGCTTAATGAAATACTGGATTACAACATCAATTACC





TAGCTTACAATTTGGCATTACTCAAGAATGCTATTGAACCTCCGACTTA





TTTGAAAGCAATGACTCTTGAAACATGTAGCATCGACATTGCAAGGAGC





CTCCGGAAGCTCTCCTGGGCCCCACTCTTGGGTGGGAGAAATCTTGAAG





GATTAGAGACGCCAGATCCCATTGAAATTACTGCAGGAGCATTAATTGT





TGGATCGGGCTACTGTGAACAGTGTGCTGCAGGAGACAATCGATTCACA





TGGTTTTTCTTGCCATCTGGTATCGAGATAGGAGGGGATCCCCGTGATA





ATCCTCCTATCCGTGTACCGTACATTGGCTCCAGGACTGATGAGAGGAG





GGTAGCCTCAATGGCATACATCAGGGGTGCCTCGAGTAGCCTAAAAGCA





GTTCTTAGACTGGCGGGAGTGTACATCTGGGCATTCGGAGATACTCTGG





AGAATTGGATAGATGCACTGGATTTGTCTCACACTAGAGTTAACATCAC





ACTTGAACAGCTGCAATCCCTCACCCCACTTCCAACCTCTGCCAATCTA





ACCCATCGGTTGGATGATGGCACAACTACCCTAAAGTTTACTCCTGCGA





GCTCTTACACCTTTTCAAGTTTCACTCATATATCAAATGATGAGCAATA





CCTGACAATTAATGACAAAACTGCAGATTCAAATATAATCTACCAACAG





TTAATGATCACTGGACTCGGAATTTTAGAAACATGGAATAATCCCCCAA





TCAATAGAACATTCGAAGAATCTACCCTACATTTGCACACTGGTGCATC





ATGTTGTGTCCGACCTGTGGACTCCTGCATCATCTCAGAAGCATTAACA





GTCAAGCCACATATTACAGTACCGTACAGCAATAAATTTGTATTTGATG





AAGACCCGCTATCTGAATATGAGACTGCAAAACTGGAATCGTTATCATT





TCAAGCCCAATTAGGCAACATTGATGCTGTAGATATGACAGGTAAATTA





ACATTATTGTCCCAATTCACTGCAAGGCAGATTATTAATGCAATCACTG





GACTCGATGAGTCTGTCTCTCTTACTAATGATGCCATTGTTGCATCAGA





CTATGTCTCCAATTGGATTAGTGAATGCATGTATACCAAATTAGATGAA





TTATTTATGTATTGTGGGTGGGAACTACTATTGGAACTATCCTATCAAA





TGTATTATCTGAGGGTAGTTGGGTGGAGTAATATAGTGGATTATTCTTA





CATGATCTTGAGAAGAATCCCGGGTGCAGCATTAAACAATCTGGCATCT





ACATTAAGTCATCCAAAACTTTTCCGACGAGCTATCAACCTAGATATAG





TTGCCCCCTTAAATGCTCCTCATTTTGCATCTCTGGACTACATCAAGAT





GAGTGTGGATGCAATACTCTGGGGCTGTAAAAGAGTCATCAATGTGCTC





TCCAATGGAGGGGACTTAGAATTAGTTGTGACATCTGAAGATAGCCTTA





TTCTCAGTGACCGATCCATGAATCTCATTGCAAGGAAATTAACTTTATT





ATCACTGATTCACCATAATGGTTTGGAACTACCAAAGATTAAGGGGTTC





TCTCCTGATGAGAAGTGTTTCGCTTTGACAGAATTTTTGAGGAAAGTGG





TGAACTCAGGGTTGAGTTCAATAGAGAACCTATCAAATTTTATGTACAA





TGTGGAGAACCCACGGCTTGCAGCATTCGCCAGCAACAATTACTACCTG





ACCAGAAAATTATTGAATTCAATACGAGATACTGAGTCGGGTCAAGTAG





CAGTCACCTCATATTATGAATCATTAGAATATATTGATAGTCTTAAGCT





AACCCCACATGTGCCTGGTACCTCATGCATTGAGGATGATAGTCTATGT





ACAAATGATTACATAATCTGGATCATAGAGTCTAATGCAAACTTGGAGA





AGTATCCAATTCCAAATAGCCCTGAGGATGATTCCAATTTCCATAACTT





TAAGTTGAATGCTCCATCGCACCATACCTTACGCCCATTAGGGTTGTCA





TCAACTGCTTGGTATAAGGGTATAAGCTGTTGCAGGTACCTTGAGCGAT





TAAAGCTACCACAAGGTGATCATTTATATATTGCAGAAGGTAGTGGTGC





CAGTATGACAATCATAGAATACCTATTCCCAGGAAGAAAGATATATTAC





AATTCTTTATTTAGTAGTGGTGACAATCCCCCACAAAGAAATTATGCAC





CAATGCCTACTCAGTTCATTGAGAGTGTCCCATACAAGCTCTGGCAAGC





ACACACAGATCAATATCCCGAGATTTTTGAGGACTTCATCCCTCTATGG





AACGGAAATGCCGCCATGACTGACATAGGAATGACAGCTTGTGTAGAAT





TCATCATCAATCGAGTCGGCCCAAGGACTTGCAGTTTAGTACATGTAGA





TTTGGAATCAAGTGCAAGCTTAAATCAACAATGCCTGTCAAAGCCGATA





ATTAATGCTATCATCACTGCTACAACTGTTTTGTGCCCTCATGGGGTGC





TTATTCTGAAATATAGTTGGTTGCCATTTACTAGATTTAGTACTTTGAT





CACTTTCTTATGGTGCTACTTTGAGAGAATCACTGTTCTTAGGAGCACA





TATTCTGGTCCAGCTAATCATGAGGTTTATTTAATTTGTATCCTTGCCA





ACAACTTTGCATTCCAGACTGTCTCGCAGGCAACAGGAATGGCGATGAC





TTTAACCGATCAAGGGTTTACTTTGATATCACCTGAAAGAATAAATCAG





TATTGGGATGGTCACTTGAAGCAAGAACGTATCGTAGCAGAAGCAATTG





ATAAGGTGGTTCTAGGAGAAGATGCTCTATTCAATTCGAGTGATAATGA





ATTAATTCTCAAATGTGGAGGGACACCAAATGCACGGAATCTTATCGAT





ATCGAGCCAGTCGCAACTTTCATAGAATTTGAACAACTGATCTGCACAA





TGTTGACAACCCACTTGAAGGAAATAATTGATATAACAAGGTCTGGAAC





CCAGGATTATGAAAGTTTATTACTCACTCCTTACAATTTAGGTCTTCTT





GGTAAAATCAGTACGATAGTGAGATTATTAACAGAAAGGATTCTAAATC





ATACTATCAGGAATTGGTTGATCCTCCCACCTTCGCTCCGGATGATCGT





GAAGCAGGACTTGGAATTCGGCATATTCAGGATTACTTCCATCCTCAAT





TCTGATCGGTTCCTGAAGCTTTCTCCAAATAGGAAATACTTGATTACAC





AATTAACTGCAGGCTACATTAGGAAATTGATTGAGGGGGATTGTAATAT





CGATCTAACCAGACCTATCCAAAAACAAATCTGGAAAGCATTAGGTTGT





GTAGTCTATTGTCACGATCCAGTAGATCAAAGGGAATCAACAGAGTTTA





TTGATATAAATATTAATGAAGAAATAGACCGCGGGATCGATGGCGAGGA





AATCTAAATATATCAAGAATCAGAATTAGTTTAAGAAAAAAGAAGAGGA





TTAATCTTGGTTTTCCCCTTGGT.






17. CVL80


The nucleic acid sequence for CVL80 is:









(SEQ ID NO: 76)


ACCAGGGGGAAAACGAAGTGGTGACTCAAATCATCGAAGACCCTCGAGA





TTACATAGGTCCGGAACCTATGGCCTTCGTGACCGACCTCGAGTCAGAG





TAGTTCAATAAGGACCTATCAAGTTTGGGCAATTTTTCGTCCCCGACAC





AAAAATGTCATCCGTGCTTAAAGCATATGAGCGATTCACACTCACTCAA





GAACTGCAAGATCAGAGTGAGGAAGGTACAATCCCACCTACAACACTAA





AACCGGTAATCAGGGTATTTATACTAACCTCTAATAACCCAGAGCTAAG





ATCCCGGCTTCTTCTATTCTGCCTACGGATTGTTCTCAGTAATGGTGCA





AGGGATTCCCATCGCTTTGGAGCATTACTTACAATGTTTTCGCTACCAT





CAGCCACAATGCTCAATCATGTCAAATTAGCTGACCAGTCACCAGAAGC





TGATATCGAAAGGGTAGAGATCGATGGCTTTGAGGAGGGATCATTCCGC





TTAATCCCCAATGCTCGTTCAGGTATGAGCCGTGGAGAGATCAATGCCT





ATGCTGCACTTGCAGAAGATCTACCTGACACACTAAACCATGCAACACC





TTTTGTTGATTCCGAAGTCGAGGGAACTGCATGGGATGAGATTGAGACT





TTCTTAGATATGTGTTACAGTGTCCTAATGCAGGCATGGATAGTGACTT





GCAAGTGCATGACTGCGCCAGACCAACCTGCTGCTTCTATTGAGAAACG





CCTGCAAAAATATCGTCAGCAAGGCAGGATCAACCCGAGATATCTCCTG





CAACCGGAGGCTCGAAGAATAATCCAGAATGTAATCCGAAAGGGAATGG





TGGTCAGACATTTCCTCACCTTTGAACTGCAGCTTGCCCGAGCACAAAG





CCTTGTATCAAATAGGTATTATGCTATGGTAGGGGATGTTGGAAAGTAT





ATAGAGAATTGTGGAATGGGAGGCTTCTTTTTGACACTAAAATATGCAT





TAGGAACCAGATGGCCCACACTTGCTTTAGCTGCATTTTCAGGAGAGCT





AACAAAGCTAAAGTCCCTCATGGCATTATACCAGACCCTTGGTGAGCAG





GCCCGATATTTGGCCCTATTGGAGTCACCACATTTGATGGATTTTGCTG





CAGCAAACTACCCACTGCTATATAGCTATGCTATGGGAATAGGCTATGT





GTTAGATGTCAACATGAGGAACTACGCTTTCTCCAGATCATACATGAAT





AAGACATATTTCCAATTGGGAATGGAAACTGCAAGAAAACAACAGGGTG





CAGTTGACATGAGGATGGCAGAAGATCTCGGTCTAACTCAAGCCGAACG





CACCGAGATGGCAAATACACTTGCCAAATTGACCACAGCAAATCGAGGG





GCAGACACCAGGGGAGGAGTCAACCCGTTCTCATCTATCACTGGGACAA





CTCAGGTGCCCGCTGCAGCAACAGGTGACACATTCGAGAGTTACATGGC





AGCGGATCGACTGAGGCAGAGATATGCTGATGCAGGCACCCACGATGAT





GAGATGCCACCATTGGAAGAGGAGGAAGAGGACGACACATCTGCAGGTC





CACGCACTGGACTAACTCTTGAACAAGTGGCCTTGGACATCCAGAACGC





AGCAGTTGGAGCTCCCATCCATACAGATGACCTGAATGCCGCACTGGGT





GATCTTGACATCTAGACAATTCAGATCCCAATCTTAAATCGACACACCT





AATTGACCAGTTAGATGGAACTACAGTGGATTCCATAAGGTTCCTGCCT





ACCATCGGCTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGC





GACTGCCGATGCCAATAACACAATCCACAATCTACAATGGATCCCACTG





ATCTGAGCTTCTCCCCAGATGAGATCAATAAGCTCATAGAGACAGGCCT





GAATACTGTGGAGTATTTTACTTCCCAACAAGTCACAGGAACATCCTCT





CTTGGAAAGAATACAATACCACCAGGGGTCACAGGACTACTAACCAATG





CTGCAGAGGCAAAGATCCAAGAGTCAACCAACCATCAGAAGGGTTCAGT





TGGTGGGGGCGCAAAACCAAAGAAACCGCGACCAAAAATTGCCATTGTG





CCAGCAGATGACAAAACGGTGCCCGGAAAGCCGATCCCAAACCCTCTAT





TAGGTCTGGACTCCACCCCGAGCACCCAAACTGTGCTTGATCTAAGTGG





GAAAACATTACCATCAGGATCCTATAAGGGGGTTAAACTTGCGAAATTT





GGAAAAGAAAATCTGATGACACGGTTCATCGAGGAACCCAGAGAGAATC





CTATCGCAACCAATTCCCCCATCGATTTTAAGAGGGGCAGGGATACCGG





CGGGTTCCATAGAAGGGAGTACTCAATCGGATGGGTGGGAGATGAAGTC





AAGGTCACTGAGTGGTGCAATCCATCCTGTTCTCCAATCACCGCTGCAG





CAAGGCGATTTGAATGCACTTGTCACCAGTGTCCAGTCACTTGCTCTGA





ATGTGAACGAGATACTTAATACAGTGAGAAATTTGGACTCTCGGATGAA





TCAACTGGAGACAAAAGTAGATCGCATTCTCTCATCTCAGTCTCTAATC





CAGACCATCAAGAATGACATAGTTGGACTTAAAGCAGGGATGGCTACTT





TAGAAGGAATGATTACAACTGTGAAAATCATGGACCCGGGAGTTCCCAG





TAATGTTACTGTGGAAGATGTACGCAAGAAACTAAGTAACCATGCTGTT





GTTGTGCCAGAATCATTCAATGATAGTTTCTTGACTCAATCTGAAGATG





TAATTTCACTTGATGAGTTGGCTCGACCAACTGCAACAAGTGTTAAGAA





GATTGTCAGGAAGGTTCCTCCTCAGAAGGATCTGACTGGATTGAAGATC





ACACTAGAGCAATTGGCAAAGGATTGCATCAGCAAACCGAAGATGAGGG





AAGAGTATCTCCTCAAAATCAACCAGGCTTCCAGTGAGGCTCAGCTAAT





TGACCTCAAGAAAGCAATCATCCGCAGTGCAATTTGATCAAGAAACACC





CAATTACACTACACTGGTATGACACTGTACTAACCCTGAGGGTTTTAGA





AAAAACGATTAACGATAAATAAGCCCGAACACTACACACCACCCGAGGC





AGCCATGCCATCCATCAGCATCCCCGCAGACCCCACCAATCCACGTCAA





TCAATAAAAGCGTTCCCAATTGTGATCAACCGTGATGGGGGTGAGAAAG





GTCGCTTGGTTAAACAACTACGCACAACCTACTTGAATGACCTAGATAC





TCATGAGCCACTGGTGACATTCGTAAATACTTATGGATTCATCTACGAA





CAGGATCGGGGAAATACCATTGTCGGAGAGGATCAACATGGGAAGAAAA





GAGAGGCTGTGACTGCTGCAATGGTTACCCTTGGATGTGGGCCTAATCT





ACCATCATTAGGGAATGTCCTGGGACAACTGAGTGAATTCCAGGTCATT





GTTAGGAAGACATCCAGCAAAGCGGAAGAGATGGTCTTTGAAATTGTTA





AGTATCCGAGAATATTTCGGGGTCATACATTAATCCAGAAAGGACTAGT





CTGTGTCTCCGCAGAAAAATTTGTTAAGTCACCAGGGAAAGTACAATCT





GGAATGGACTATCTCTTCATTCCGACATTTCTGTCAGTGACTTACTGTC





CAGCTGCAATCAAATTTCAGGTACCTGGCCCCATGTTGAAAATGAGATC





AAGATACACTCAGAGCTTACAACTTGAACTAATGATAAGAATCCTGTGT





AAGCCCGATTCGCCACTTATGAAGGTCCATATCCCTGACAAGGAAGGAA





GAGGATGTCTTGTATCAGTATGGTTGCATGTATGCAATATCTTCAAATC





AGGAAACAAGAATGGCAGTGAGTGGCAGGAATACTGGATGAGAAAGTGT





GCTAACATGCAACTTGAAGTGTCGATTGCAGATATGTGGGGACCAACTA





TCATAATTCATGCCAGAGGTCACATTCCCAAAAGTGCTAAGTTGTTTTT





TGGAAAGGGTGGATGGAGCTGCCATCCACTTCACGAAGTTGTTCCAAGT





GTCACTAAAACACTATGGTCCGTGGGCTGTGAGATTACAAAGGCGAAGG





CAATAATACAAGAGAGTAGCATCTCTCTTCTCGTGGAGACTACTGACAT





CATAAGTCCAAAAGTCAAAATTTCATCTAAGCATCGCCGCTTTGGGAAA





TCAAATTGGGGTCTGTTCAAGAAAACCAAATCACTGCCCAACCTGACGG





AGCTGGAATGACTGACCCCCAATCGAGACTACACCACCTCAAACTATAG





GTGGGTGGTACCTCAGTGATTAATCTCGTAAGCACTGATCGTAGGCTAC





AACACACTAATATTATCCAGATTAGAGAGCTTAATTAGCTCTGTATTAA





TAATAACACTACTATTCCAATAACTGGAATCACCAGCTTGATTTATCTC





CAAAATGATTCAAAGAAAACAAATCATATTAAGACTATCCTAAGCACGA





ACCCATATCGTCCTTCAAATCATGGGTACTATAATTCAATTTCTGGTGG





TCTCCTGTCTATTGGCAGGAGCAGGCAGTCTTGATCCAGCAGCCCTCAT





GCAAATCGGTGTCATTCCAACAAATGTCCGGCAACTTATGTATTATACT





GAGGCCTCATCAGCATTCATTGTTGTGAAGTTAATGCCTACAATTGACT





CGCCGATTAGTGGATGTAATATAACATCAATTTCAAGCTATAATGCAAC





AGTGACAAAACTCCTACAGCCGATCGGTGAGAATTTGGAGACGATTAGG





AACCAGTTGATTCCAACTCGGAGGAGACGCCGGTTTGCAGGGGTGGTGA





TTGGATTAGCTGCATTAGGAGTAGCTACTGCCGCACAGGTCACTGCCGC





AGTAGCACTAGTAAAGGCAAATGAAAATGCTGCGGCTATACTCAATCTC





AAAAATGCAATCCAAAAAACAAATGCAGCAGTTGCAGATGTGGTCCAGG





CCACACAATCACTAGGAACaGCAGTTCAAGCAGTTCAAGATCACATAAA





CAGTGTGGTAAGTCCAGCAATTACAGCAGCCAATTGTAAAGCCCAAGAT





GCTATCATTGGCTCAATCCTCAATCTCTATTTGACCGAGTTGACAACTA





TCTTCCACAATCAAATTACAAACCCTGCATTGAGTCCTATTACAATTCA





AGCTTTAAGGATCCTACTAGGGAGTACCTTGCCGACTGTGGTCGAAAAA





TCTTTCAATACCCAGATAAGTGCGGCTGAGCTTCTCTCATCAGGGTTAT





TGACAGGCCAGATTGTGGGATTAGATTTGACCTATATGCAGATGGTCAT





AAAAATTGAGCTGCCAACTTTAACTGTACAACCTGCAACCCAGATCATA





GATCTGGCCACCATTTCTGCATTCATTAACAATCAAGAAGTCATGGCCC





AATTACCAACACGTGTTATTGTGACTGGCAGCTTGATCCAAGCCTATCC





CGCATCGCAATGCACTATTACACCCAACACTGTGTACTGTAGGTATAAT





GATGCCCAAGTACTCTCAGATGATACGATGGCTTGCCTCCAAGGTAACT





TGACAAGATGCACCTTCTCTCCAGTGGTTGGGAGCTTTCTCACTCGATT





CGTGCTGTTCGATGGAATAGTTTATGCAAATTGCAGGTCGATGTTGTGC





AAGTGCATGCAGCCTGCTGCTGTGATCCTACAGCCGAGTTCATCCCCTG





TAACTGTCATTGACATGTACAAATGTGTGAGTCTGCAGCTTGACAATCT





CAGATTCACCATCACTCAATTGGCCAATGTAACCTACAATAGCACCATC





AAGCTTGAAACATCCCAGATCTTGCCTATTGATCCGTTGGATATATCCC





AGAATCTAGCTGCGGTGAATAAGAGTCTAAGTGATGCACTACAACACTT





AGCACAAAGTGACACATACCTTTCTGCAATCACATCAGCTACGACTACA





AGTGTATTATCCATAATAGCAATCTGTCTTGGATCGTTAGGTTTAATAT





TAATAATCTTGCTCAGTGTAGTTGTGTGGAAGTTATTGACCATTGTCGC





TGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAATTCAGCATTC





CACCACTCACGATCTGATCTCAGTGAGAAAAATCAACCTGCAACTCTTG





GAACAAGATAAGACAGTCATCCATTAGTAATTTTTAAGAAAAAAACGAT





AGGACCGAAACTAGTATTGAAAGAACCGTCTCGGTCAATCTAGGTAATC





GAGCTGcTACCGTCTCGGAAAGCTCAAATCATGCTGCCTGATCCGGAAG





ATCCGGAAAGCAAAAAAGCTACAAGGAGAACAGGAAACCTAATTATCTG





CTTCCTATTCATCTTCTTTCCGTTTGTAAACTTCATTGTTCCAACTCTA





AGACACTTGCTGTCCTAACACCTGCTATAGGCTATCCACTGCATCATCT





CTTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCC





GGTGCCAACAACACAATCCACAATCTACAGTCGACGCGGCCGCCACCat





gttcgtcttcctggtcctgctgcctctggtctcctcacagtgcgtcaat





ctgacaactcggactcagctgccacctgcttatactaatagcttcacca





gaggcgtgtactatcctgacaaggtgtttagaagctccgtgctgcactc





tacacaggatctgtttctgccattctttagcaacgtgacctggttccac





GTGatcagcggcaccaatggcacaaagcggttcgacaatcccgtgctgc





cttttaacgatggcgtgtacttcgcctctATCgagaagagcaacatcat





cagaggctggatctttggcaccacactggactccaagacacagtctctg





ctgatcgtgaacaatgccaccaacgtggtcatcaaggtgtgcgagttcc





agttttgtaatgatcccttcctgGATcacaagaacaataagagctggat





ggagtccgagtttagagtgtattctagcgccaacaactgcacatttgag





tacgtgagccagcctttcctgatggacctggagggcaagcagggcaatt





tcaagaacctgagggagttcgtgtttaagaatatcgacggctacttcaa





aatctactctaagcacacccccATCATCgtgcgcGAGCCTGAGgacctg





cctcagggcttcagcgccctggagcccctggtggatctgcctatcggca





tcaacatcacccggtttcagacactgctggccctgcacagaagctacct





gacacccggcgactcctctagcggatggaccgccggcgctgccgcctac





tatgtgggctacctccagccccggaccttcctgctgaagtacaacgaga





atggcaccatcacagacgcagtggattgcgccctggaccccctgagcga





gacaaagtgtacactgaagtcctttaccgtggagaagggcatctatcag





acatccaatttcagggtgcagccaaccgagtctatcgtgcgctttccta





atatcacaaacctgtgcccatttGACgaggtgttcaacgcaacccgctt





cgccagcgtgtacgcctggaataggaagcggatcagcaactgcgtggcc





gactatagcgtgctgtacaacCTGgccCCCttcTTCacctttaagtgct





atggcgtgtcccccacaaagctgaatgacctgtgctttaccaacgtcta





cgccgattctttcgtgatcaggggcgacgaggtgcgccagatcgccccc





ggccagacaggcAATatcgcagactacaattataagctgccagacgatt





tcaccggctgcgtgatcgcctggaacagcaacAAGctggattccaaagt





gTCCggcaactacaattatctgtaccggctgtttagaaagagcaatctg





aagcccttcgagagggacatctctacagaaatctaccaggccggcAATA





AGccttgcaatggcgtgGCCggctttaactgttatttcccactcAAGtc





ctacTCCttcCGCcccacaTATggcgtgggcCACcagccttaccgcgtg





gtggtgctgagctttgagctgctgcacgccccagcaacagtgtgcggcc





ccaagaagtccaccaatctggtgaagaacaagtgcgtgaacttcaactt





caacggcctgAAGggcacaggcgtgctgaccgagtccaacaagaagttc





ctgccatttcagcagttcggcagggacatcgcagataccacagacgccg





tgcgcgacccacagaccctggagatcctggacatcacaccctgctcttt





cggcggcgtgagcgtgatcacacccggcaccaatacaagcaaccaggtg





gccgtgctgtatcagGGCgtgaattgtaccgaggtgcccgtggctatcc





acgccgatcagctgaccccaacatggcgggtgtacagcaccggctccaa





cgtcttccagacaagagccggatgcctgatcggagcagagTACgtgaac





aattcctatgagtgcgacatcccaatcggcgccggcatctgtgcctctt





accagacccagacaAAGtctCACagaagagcccggagcgtggcctccca





gtctatcatcgcctataccatgtccctgggcgccgagaacagcgtggcc





tactctaacaatagcatcgccatcccaaccaacttcacaatctctgtga





ccacagagatcctgcccgtgtccatgaccaagacatctgtggactgcac





aatgtatatctgtggcgattctaccgagtgcagcaacctgctgctccag





tacggcagcttttgtacccagctgAAGagagccctgacaggcatcgccg





tggagcaggataagaacacacaggaggtgttcgcccaggtgaagcaaat





ctacaagaccccccctatcaagTACtttggcggcttcaatttttcccag





atcctgcctgatccatccaagccttctaagcggagctttatcgaggacc





tgctgttcaacaaggtgaccctggccgatgccggcttcatcaagcagta





tggcgattgcctgggcgacatcgcagccagggacctgatctgcgcccag





aagtttAAGggcctgaccgtgctgccacccctgctgacagatgagatga





tcgcacagtacacaagcgccctgctggccggcaccatcacatccggatg





gaccttcggcgcaggagccgccctccagatcccctttgccatgcagatg





gcctataggttcaacggcatcggcgtgacccagaatgtgctgtacgaga





accagaagctgatcgccaatcagtttaactccgccatcggcaagatcca





ggacagcctgtcctctacagccagcgccctgggcaagctccaggatgtg





gtgaatCACaacgcccaggccctgaataccctggtgaagcagctgagca





gcAAGttcggcgccatctctagcgtgctgaatgacatcTTTagccggct





ggacaaggtggaggcagaggtgcagatcgaccggctgatcaccggccgg





ctccagagcctccagacctatgtgacacagcagctgatcagggccgccg





agatcagggccagcgccaatctggcagcaaccaagatgtccgagtgcgt





gctgggccagtctaagagagtggacttttgtggcaagggctatcacctg





atgtccttccctcagtctgccccacacggcgtggtgtttctgcacgtga





cctacgtgcccgcccaggagaagaacttcaccacagcccctgccatctg





ccacgatggcaaggcccactttccaagggagggcgtgttcgtgtccaac





ggcacccactggtttgtgacacagcgcaatttctacgagccccagatca





tcaccacagacaacaccttcgtgagcggcaactgtgacgtggtcatcgg





catcgtgaacaataccgtgtatgatccactccagcccgagctggacagc





tttaaggaggagctggataagtatttcaagaatcacacctcccctgacg





tggatctgggcgacatcagcggcatcaatgcctccgtggtgaacatcca





gaaggagatcgaccgcctgaacgaggtggctaagaatctgaacgagagc





ctgatcgacctccaggagctgggcaagtatgagcagtacatcaagtggc





cctggtacatctggctgggcttcatcgccggcctgatcgccatcgtgat





ggtgaccatcatgctgtgctgtatgacatcctgctgttcttgcctgaag





ggctgctgtagctgtggctcctgctgtAAGTTATTGACCATTGTCGTTG





CTAATCGAAATAGAATGGAGAATTTTGTTTATCATAAATGAGCTAGCCT





CCTGCCATACTTCCTACTCACATCATATCTATTTTAAAGAAAAAATAGG





CCCGAACACTAATCGTGCCGGCAGTGCCACTGCACACACAACACTACAC





ATACAATACACTACAATGGTTGCAGAAGATGCCCCTGTTAGGGGCACTT





GCCGAGTATTATTTCGAACAACAACTTTAATTTTTCTATGCACACTATT





AGCATTAAGCATCTCTATCCTTTATGAGAGTTTAATAACCCAAAAGCAA





ATCATGAGCCAAGCAGGCTCAACTGGATCTAATTCTAGATTAGGAAGTA





TCACTGATCTTCTTAATAATATTCTCTCTGTCGCAAATCAGATTATATA





TAACTCTGCAGTCGCTCTACCTCTACAATTGGACACTCTTGAATCAACA





CTCCTTACAGCCATTAAGTCTCTTCAAACAAGTGACAAGCTAGAACAGA





ACTGCTCGTGGGGTGCTGCACTGATTAATGATAATAGATACATTAATGG





CATCAATCAGTTCTATTTCTCAATTGCTGAGGGTCGCAAGCTGACACTT





GGCCCACTTCTTAATATACCTAGTTTCATTCCAACTGCCACGACACCAG





AGGGCTGCACCAGGATCCCATCATTCTCGCTCACCAAGACACACTGGTG





TTATACACACAATGTTATCCTGAATGGATGCCAGGATCATGTATCCTCA





AATCAATTTGTTTCCATGGGAATCATTGAACCCACTTCTGCCGGGTTTC





CATCCTTTCGAACCCTAAAGACTCTATATCTCAGCGATGGGGTCAATCG





TAAGAGCTGCTCTATCAGTACAGTTCCGGGGGGTTGTATGATGTACTGT





TTCGTCTCTACTCAACCAGAGAGGGATGACTACTTTTCTACCGCTCCTC





CAGAACAACGAATTATTATAATGTACTATAATGATACAATCGTGGAGCG





CATAATTAATCCACCCGGGGTACTAGATGTATGGGCAACATTGAACCCA





GGAACAGGAAGCGGGGTATATTATTTAGGTTGGGTACTCTTTCCAATAT





ATGGCGGCGTGATTAAAGATACGAGTTTATGGAATAATCAAGCAAATAA





ATACTTTATCCCCCAGATGGTTGCTGCTCTCTGCTCACAAAACCAGGCA





ACTCAAGTCCAAAATGCTAAGTCATCATACTATAGCAGCTGGTTTGGCA





ATCGAATGATTCAGTCTGGGATCCTGGCATGTCCTCTTCAACAGGATCT





AACCAATGAGTGTTTAGTTCTGCCCTTTTCTAATGATCAGGTGCTTATG





GGTGCTGAAGGGAGATTATACATGTATGGTGACTCGGTGTATTACTACC





AAAGAAGCAATAGTTGGTGGCCTATGACCATGCTGTATAAGGTAACCAT





AACATTCACTAATGGTCAGCCATCTGCTATATCAGCTCAGAATGTGCCC





ACACAGCAGGTCCCTAGACCTGGGACAGGAAGCTGCTCTGCAACAAATA





GATGTCCCGGTTTTTGCTTGAAAGGAGTGTATGCTGATGCCTGGTTACT





GACCAACCCTTCGTCTACCAGTACATTTGGATCAGAAGCAACCTTCACT





GGTTCTTATCTCAACGCAGCAACTCAGCGTATCAATCCGACGATGTATA





TCGCGAACAACACACAGATCATAAGCTCACAGCAATTTGGATCAAGCGG





TCAAGAAGCAGCATATGGCCACACAACTTGTTTTAGGGACACAGGCTCT





GTTATGGTATACTGTATCTATATTATTGAATTGTCCTCATCTCTCTTAG





GACAATTTCAGATTGTCCCATTTATCCGTCAGGTGACACTATCCTAAAG





GCAGAAGCCTCCAGGTCTGACCCAGCCAATCAAAGCATTATACCAGACC





ATGGAATGCATACCAAACATTATTGACACTAATGACACACAAAATTGGT





TTTAAGAAAAACCAAGAGAACAATAGGCCAGAATGGCTGGGTCTCGGGA





GATATTACTCCCTGAAGTCCATCTCAATTCACCAATTGTAAAGCATAAG





CTATACTATTACATTCTACTTGGAAACCTCCCAAATGAGATCGACATTG





ACGATTTAGGTCCATTACATAATCAAAATTGGAATCAAATAGCACATGA





AGAGTCTAACTTAGCCCAACGCTTGGTAAATGTAAGAAATTTTCTAATT





ACCCACATCCCTGATCTTAGAAAGGGCCATTGGCAAGAGTATGTCAATG





TAATACTGTGGCCGCGAATTCTTCCCTTGATCCCGGATTTTAAAATCAA





TGACCAATTGCCTCTACTCAAAAATTGGGACAAGTTAGTTAAAGAATCA





TGTTCAGTAATCAATGCGGGTACTTCCCAGTGCATTCAGAATCTCAGCT





ATGGACTGACAGGTCGTGGGAACCTCTTTACACGATCACGTGAACTCTC





TGGTGACCGCAGGGATATTGATCTTAAGACGGTTGTGGCAGCATGGCAT





GACTCAGACTGGAAAAGAATAAGTGATTTTTGGATTATGATCAAATTCC





AGATGAGACAATTAATTGTTAGGCAAACAGATCATAATGATCCTGATTT





AATCACGTATATCGAAAATAGAGAAGGCATAATCATCATAACCCCTGAA





CTGGTAGCATTATTTAACACTGAGAATCATACACTAACATACATGACCT





TTGAAATTGTACTGATGGTTTCAGATATGTACGAAGGTCGTCACAACAT





TTTATCACTATGCACAGTTAGCACTTACCTGAATCCTCTGAAGAAAAGA





ATAACATATTTATTGAGCCTTGTAGATAACTTAGCTTTTCAGATAGGTG





ATGCTGTATATAACATAATTGCTTTGCTAGAATCCTTTGTATATGCACA





GTTGCAAATGTCAGATCCCATCCCAGAACTCAGAGGACAATTCCATGCA





TTCGTATGTTCTGAGATTCTTGATGCACTAAGGGGAACTAATAGTTTCA





CCCAGGATGAATCAAGAACTGTGACAACCAATTTGATATCCCCATTCCA





AGATCTGACCCCAGATCTTACGGCTGAATTGCTCTGTATAATGAGGCTT





TGGGGACACCCCATGCTCACCGCCAGTCAAGCTGCGGGAAAGGTACGCG





AGTCCATGTGTGCTGGAAAAGTATTAGACTTTCCCACCATTATGAAAAC





ACTAGCCTTTTTCCATACTATTCTGATCAATGGATACAGGAGGAAGCAT





CATGGAGTATGGCCACCCTTAAACTTACCGGGTAATGCTTCAAAGGGTC





TCACGGAACTTATGAATGACAATACTGAGATAAGCTATGAATTCACACT





TAAGCATTGGAAGGAAATCTCTCTTATAAAATTCAAGAAATGTTTTGAT





GCAGACGCAGGTGAGGAACTCAGTATATTTATGAAAGATAAAGCAATTA





GTGCCCCAAAACAAGATTGGATGAGTGTGTTTAGAAGAAGCCTAATCAA





ACAGCGCCATCAGCATCATCAGGTCCCCCTACCAAATCCATTCAATCGA





CGGCTATTGCTAAACTTTCTCGGAGATGACAAATTCGACCCGAATGTGG





AGCTACAGTATGTAACATCAGGTGAGTATCTACATGATGACACGTTTTG





TGCATCATATTCACTAAAAGAGAAGGAAATTAAACCTGATGGTCGAATT





TTTGCAAAGTTGACTAAGAGAATGAGATCATGTCAAGTTATAGCAGAAT





CTCTTTTAGCGAACCATGCTGGGAAGTTAATGAAAGAGAATGGTGTTGT





GATGAATCAGCTATCATTAACAAAATCACTATTAACAATGAGTCAGATT





GGAATAATATCCGAGAAAGCTAGAAAATCGACTCGAGATAACATAAATC





AACCTGGTTTCCAGAATATCCAGAGAAATAAATCACATCACTCCAAGCA





AGTCAATCAGCGAGATCCAAGTGATGACTTTGAATTGGCAGCATCTTTT





TTAACTACTGATCTCAAAAAATATTGTTTACAATGGAGGTACCAGACAA





TTATCCCATTTGCTCAATCATTAAACAGAATGTATGGTTATCCTCATCT





CTTTGAGTGGATTCACTTACGGCTAATGCGTAGTACACTTTACGTGGGG





GATCCCTTCAACCCACCAGCAGATACCAGTCAATTTGATCTAGATAAAG





TAATTAATGGAGATATCTTCATTGTATCACCCAGAGGTGGAATTGAAGG





GCTATGTCAAAAGGCTTGGACAATGATATCTATCTCTGTGATAATTCTA





TCTGCCACAGAGTCTGGCACACGAGTAATGAGTATGGTGCAGGGAGATA





ATCAAGCAATTGCTGTCACCACACGAGTACCAAGGAGCCTGCCGACTCT





TGAGAAAAAGACTATTGCTTTTAGATCTTGTAATCTATTCTTTGAGAGG





TTAAAATGTAATAATTTTGGATTAGGTCACCATTTGAAAGAACAAGAGA





CTATCATTAGTTCTCACTTCTTTGTTTATAGCAAGAGAATATTCTATCA





GGGGAGGATTCTAACGCAAGCCTTAAAAAATGCTAGTAAGCTCTGCTTG





ACAGCTGATGTCCTAGGAGAATGTACCCAATCATCATGTTCTAATCTTG





CAACTACTGTCATGAGGTTAACTGAGAATGGTGTTGAAAAAGATATCTG





TTTCTACTTGAATATCTATATGACCATCAAACAGCTCTCCTATGATATC





ATCTTCCCTCAAGTGTCAATTCCTGGAGATCAGATCACATTAGAATACA





TAAATAATCCACACCTGGTATCACGATTGGCTCTTCTGCCATCCCAGCT





AGGAGGTCTAAACTACCTGTCATGCAGTAGGCTGTTCAATCGAAACATA





GGCGACCCGGTGGTTTCCGCAGTTGCAGATCTTAAGAGATTAATTAAAT





CAGGATGTATGGATTACTGGATCCTTTATAACTTATTAGGGAGAAAACC





GGGAAACGGCTCATGGGCTACTTTAGCAGCTGACCCGTACTCAATCAAT





ATAGAGTATCAATACCCCCCAACTACAGCTCTTAAGAGGCACACCCAAC





AAGCTCTGATGGAACTCAGTACGAATCCAATGTTACGTGGCATATTCTC





TGACAATGCACAGGCAGAAGAAAATAATCTTGCTAGATTTCTCCTGGAT





AGGGAGGTGATCTTTCCGCGTGTAGCTCACATCATCATTGAGCAAACCA





GTGTCGGGAGGAGAAAACAGATTCAAGGATATTTGGATTCAACTAGATC





GATAATGAGTAAATCACTAGAAATTAAGCCCTTGTCCAATAGGAAGCTT





AATGAAATACTGGATTACAACATCAATTACCTAGCTTACAATTTGGCAT





TACTCAAGAATGCTATTGAACCTCCGACTTATTTGAAAGCAATGACTCT





TGAAACATGTAGCATCGACATTGCAAGGAGCCTCCGGAAGCTCTCCTGG





GCCCCACTCTTGGGTGGGAGAAATCTTGAAGGATTAGAGACGCCAGATC





CCATTGAAATTACTGCAGGAGCATTAATTGTTGGATCGGGCTACTGTGA





ACAGTGTGCTGCAGGAGACAATCGATTCACATGGTTTTTCTTGCCATCT





GGTATCGAGATAGGAGGGGATCCCCGTGATAATCCTCCTATCCGTGTAC





CGTACATTGGCTCCAGGACTGATGAGAGGAGGGTAGCCTCAATGGCATA





CATCAGGGGTGCCTCGAGTAGCCTAAAAGCAGTTCTTAGACTGGCGGGA





GTGTACATCTGGGCATTCGGAGATACTCTGGAGAATTGGATAGATGCAC





TGGATTTGTCTCACACTAGAGTTAACATCACACTTGAACAGCTGCAATC





CCTCACCCCACTTCCAACCTCTGCCAATCTAACCCATCGGTTGGATGAT





GGCACAACTACCCTAAAGTTTACTCCTGCGAGCTCTTACACCTTTTCAA





GTTTCACTCATATATCAAATGATGAGCAATACCTGACAATTAATGACAA





AACTGCAGATTCAAATATAATCTACCAACAGTTAATGATCACTGGACTC





GGAATTTTAGAAACATGGAATAATCCCCCAATCAATAGAACATTCGAAG





AATCTACCCTACATTTGCACACTGGTGCATCATGTTGTGTCCGACCTGT





GGACTCCTGCATCATCTCAGAAGCATTAACAGTCAAGCCACATATTACA





GTACCGTACAGCAATAAATTTGTATTTGATGAAGACCCGCTATCTGAAT





ATGAGACTGCAAAACTGGAATCGTTATCATTTCAAGCCCAATTAGGCAA





CATTGATGCTGTAGATATGACAGGTAAATTAACATTATTGTCCCAATTC





ACTGCAAGGCAGATTATTAATGCAATCACTGGACTCGATGAGTCTGTCT





CTCTTACTAATGATGCCATTGTTGCATCAGACTATGTCTCCAATTGGAT





TAGTGAATGCATGTATACCAAATTAGATGAATTATTTATGTATTGTGGG





TGGGAACTACTATTGGAACTATCCTATCAAATGTATTATCTGAGGGTAG





TTGGGTGGAGTAATATAGTGGATTATTCTTACATGATCTTGAGAAGAAT





CCCGGGTGCAGCATTAAACAATCTGGCATCTACATTAAGTCATCCAAAA





CTTTTCCGACGAGCTATCAACCTAGATATAGTTGCCCCCTTAAATGCTC





CTCATTTTGCATCTCTGGACTACATCAAGATGAGTGTGGATGCAATACT





CTGGGGCTGTAAAAGAGTCATCAATGTGCTCTCCAATGGAGGGGACTTA





GAATTAGTTGTGACATCTGAAGATAGCCTTATTCTCAGTGACCGATCCA





TGAATCTCATTGCAAGGAAATTAACTTTATTATCACTGATTCACCATAA





TGGTTTGGAACTACCAAAGATTAAGGGGTTCTCTCCTGATGAGAAGTGT





TTCGCTTTGACAGAATTTTTGAGGAAAGTGGTGAACTCAGGGTTGAGTT





CAATAGAGAACCTATCAAATTTTATGTACAATGTGGAGAACCCACGGCT





TGCAGCATTCGCCAGCAACAATTACTACCTGACCAGAAAATTATTGAAT





TCAATACGAGATACTGAGTCGGGTCAAGTAGCAGTCACCTCATATTATG





AATCATTAGAATATATTGATAGTCTTAAGCTAACCCCACATGTGCCTGG





TACCTCATGCATTGAGGATGATAGTCTATGTACAAATGATTACATAATC





TGGATCATAGAGTCTAATGCAAACTTGGAGAAGTATCCAATTCCAAATA





GCCCTGAGGATGATTCCAATTTCCATAACTTTAAGTTGAATGCTCCATC





GCACCATACCTTACGCCCATTAGGGTTGTCATCAACTGCTTGGTATAAG





GGTATAAGCTGTTGCAGGTACCTTGAGCGATTAAAGCTACCACAAGGTG





ATCATTTATATATTGCAGAAGGTAGTGGTGCCAGTATGACAATCATAGA





ATACCTATTCCCAGGAAGAAAGATATATTACAATTCTTTATTTAGTAGT





GGTGACAATCCCCCACAAAGAAATTATGCACCAATGCCTACTCAGTTCA





TTGAGAGTGTCCCATACAAGCTCTGGCAAGCACACACAGATCAATATCC





CGAGATTTTTGAGGACTTCATCCCTCTATGGAACGGAAATGCCGCCATG





ACTGACATAGGAATGACAGCTTGTGTAGAATTCATCATCAATCGAGTCG





GCCCAAGGACTTGCAGTTTAGTACATGTAGATTTGGAATCAAGTGCAAG





CTTAAATCAACAATGCCTGTCAAAGCCGATAATTAATGCTATCATCACT





GCTACAACTGTTTTGTGCCCTCATGGGGTGCTTATTCTGAAATATAGTT





GGTTGCCATTTACTAGATTTAGTACTTTGATCACTTTCTTATGGTGCTA





CTTTGAGAGAATCACTGTTCTTAGGAGCACATATTCTGGTCCAGCTAAT





CATGAGGTTTATTTAATTTGTATCCTTGCCAACAACTTTGCATTCCAGA





CTGTCTCGCAGGCAACAGGAATGGCGATGACTTTAACCGATCAAGGGTT





TACTTTGATATCACCTGAAAGAATAAATCAGTATTGGGATGGTCACTTG





AAGCAAGAACGTATCGTAGCAGAAGCAATTGATAAGGTGGTTCTAGGAG





AAGATGCTCTATTCAATTCGAGTGATAATGAATTAATTCTCAAATGTGG





AGGGACACCAAATGCACGGAATCTTATCGATATCGAGCCAGTCGCAACT





TTCATAGAATTTGAACAACTGATCTGCACAATGTTGACAACCCACTTGA





AGGAAATAATTGATATAACAAGGTCTGGAACCCAGGATTATGAAAGTTT





ATTACTCACTCCTTACAATTTAGGTCTTCTTGGTAAAATCAGTACGATA





GTGAGATTATTAACAGAAAGGATTCTAAATCATACTATCAGGAATTGGT





TGATCCTCCCACCTTCGCTCCGGATGATCGTGAAGCAGGACTTGGAATT





CGGCATATTCAGGATTACTTCCATCCTCAATTCTGATCGGTTCCTGAAG





CTTTCTCCAAATAGGAAATACTTGATTACACAATTAACTGCAGGCTACA





TTAGGAAATTGATTGAGGGGGATTGTAATATCGATCTAACCAGACCTAT





CCAAAAACAAATCTGGAAAGCATTAGGTTGTGTAGTCTATTGTCACGAT





CCAGTAGATCAAAGGGAATCAACAGAGTTTATTGATATAAATATTAATG





AAGAAATAGACCGCGGGATCGATGGCGAGGAAATCTAAATATATCAAGA





ATCAGAATTAGTTTAAGAAAAAAGAAGAGGATTAATCTTGGTTTTCCCC





TTGGT.






18. CVL86


The nucleic acid sequence for CVL86 is:









(SEQ ID NO: 77)


ACCAGGGGGAAAACGAAGTGGTGACTCAAATCATCGAAGACCCTCGAGA





TTACATAGGTCCGGAACCTATGGCCTTCGTGACCGACCTCGAGTCAGAG





TAGTTCAATAAGGACCTATCAAGTTTGGGCAATTTTTCGTCCCCGACAC





AAAAATGTCATCCGTGCTTAAAGCATATGAGCGATTCACACTCACTCAA





GAACTGCAAGATCAGAGTGAGGAAGGTACAATCCCACCTACAACACTAA





AACCGGTAATCAGGGTATTTATACTAACCTCTAATAACCCAGAGCTAAG





ATCCCGGCTTCTTCTATTCTGCCTACGGATTGTTCTCAGTAATGGTGCA





AGGGATTCCCATCGCTTTGGAGCATTACTTACAATGTTTTCGCTACCAT





CAGCCACAATGCTCAATCATGTCAAATTAGCTGACCAGTCACCAGAAGC





TGATATCGAAAGGGTAGAGATCGATGGCTTTGAGGAGGGATCATTCCGC





TTAATCCCCAATGCTCGTTCAGGTATGAGCCGTGGAGAGATCAATGCCT





ATGCTGCACTTGCAGAAGATCTACCTGACACACTAAACCATGCAACACC





TTTTGTTGATTCCGAAGTCGAGGGAACTGCATGGGATGAGATTGAGACT





TTCTTAGATATGTGTTACAGTGTCCTAATGCAGGCATGGATAGTGACTT





GCAAGTGCATGACTGCGCCAGACCAACCTGCTGCTTCTATTGAGAAACG





CCTGCAAAAATATCGTCAGCAAGGCAGGATCAACCCGAGATATCTCCTG





CAACCGGAGGCTCGAAGAATAATCCAGAATGTAATCCGAAAGGGAATGG





TGGTCAGACATTTCCTCACCTTTGAACTGCAGCTTGCCCGAGCACAAAG





CCTTGTATCAAATAGGTATTATGCTATGGTAGGGGATGTTGGAAAGTAT





ATAGAGAATTGTGGAATGGGAGGCTTCTTTTTGACACTAAAATATGCAT





TAGGAACCAGATGGCCCACACTTGCTTTAGCTGCATTTTCAGGAGAGCT





AACAAAGCTAAAGTCCCTCATGGCATTATACCAGACCCTTGGTGAGCAG





GCCCGATATTTGGCCCTATTGGAGTCACCACATTTGATGGATTTTGCTG





CAGCAAACTACCCACTGCTATATAGCTATGCTATGGGAATAGGCTATGT





GTTAGATGTCAACATGAGGAACTACGCTTTCTCCAGATCATACATGAAT





AAGACATATTTCCAATTGGGAATGGAAACTGCAAGAAAACAACAGGGTG





CAGTTGACATGAGGATGGCAGAAGATCTCGGTCTAACTCAAGCCGAACG





CACCGAGATGGCAAATACACTTGCCAAATTGACCACAGCAAATCGAGGG





GCAGACACCAGGGGAGGAGTCAACCCGTTCTCATCTATCACTGGGACAA





CTCAGGTGCCCGCTGCAGCAACAGGTGACACATTCGAGAGTTACATGGC





AGCGGATCGACTGAGGCAGAGATATGCTGATGCAGGCACCCACGATGAT





GAGATGCCACCATTGGAAGAGGAGGAAGAGGACGACACATCTGCAGGTC





CACGCACTGGACTAACTCTTGAACAAGTGGCCTTGGACATCCAGAACGC





AGCAGTTGGAGCTCCCATCCATACAGATGACCTGAATGCCGCACTGGGT





GATCTTGACATCTAGACAATTCAGATCCCAATCTTAAATCGACACACCT





AATTGACCAGTTAGATGGAACTACAGTGGATTCCATAAGGTTCCTGCCT





ACCATCGGCTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGC





GACTGCCGATGCCAATAACACAATCCACAATCTACAATGGATCCCACTG





ATCTGAGCTTCTCCCCAGATGAGATCAATAAGCTCATAGAGACAGGCCT





GAATACTGTGGAGTATTTTACTTCCCAACAAGTCACAGGAACATCCTCT





CTTGGAAAGAATACAATACCACCAGGGGTCACAGGACTACTAACCAATG





CTGCAGAGGCAAAGATCCAAGAGTCAACCAACCATCAGAAGGGTTCAGT





TGGTGGGGGCGCAAAACCAAAGAAACCGCGACCAAAAATTGCCATTGTG





CCAGCAGATGACAAAACGGTGCCCGGAAAGCCGATCCCAAACCCTCTAT





TAGGTCTGGACTCCACCCCGAGCACCCAAACTGTGCTTGATCTAAGTGG





GAAAACATTACCATCAGGATCCTATAAGGGGGTTAAACTTGCGAAATTT





GGAAAAGAAAATCTGATGACACGGTTCATCGAGGAACCCAGAGAGAATC





CTATCGCAACCAATTCCCCCATCGATTTTAAGAGGGGCAGGGATACCGG





CGGGTTCCATAGAAGGGAGTACTCAATCGGATGGGTGGGAGATGAAGTC





AAGGTCACTGAGTGGTGCAATCCATCCTGTTCTCCAATCACCGCTGCAG





CAAGGCGATTTGAATGCACTTGTCACCAGTGTCCAGTCACTTGCTCTGA





ATGTGAACGAGATACTTAATACAGTGAGAAATTTGGACTCTCGGATGAA





TCAACTGGAGACAAAAGTAGATCGCATTCTCTCATCTCAGTCTCTAATC





CAGACCATCAAGAATGACATAGTTGGACTTAAAGCAGGGATGGCTACTT





TAGAAGGAATGATTACAACTGTGAAAATCATGGACCCGGGAGTTCCCAG





TAATGTTACTGTGGAAGATGTACGCAAGAAACTAAGTAACCATGCTGTT





GTTGTGCCAGAATCATTCAATGATAGTTTCTTGACTCAATCTGAAGATG





TAATTTCACTTGATGAGTTGGCTCGACCAACTGCAACAAGTGTTAAGAA





GATTGTCAGGAAGGTTCCTCCTCAGAAGGATCTGACTGGATTGAAGATC





ACACTAGAGCAATTGGCAAAGGATTGCATCAGCAAACCGAAGATGAGGG





AAGAGTATCTCCTCAAAATCAACCAGGCTTCCAGTGAGGCTCAGCTAAT





TGACCTCAAGAAAGCAATCATCCGCAGTGCAATTTGATCAAGAAACACC





CAATTACACTACACTGGTATGACACTGTACTAACCCTGAGGGTTTTAGA





AAAAACGATTAACGATAAATAAGCCCGAACACTACACACCACCCGAGGC





AGCCATGCCATCCATCAGCATCCCCGCAGACCCCACCAATCCACGTCAA





TCAATAAAAGCGTTCCCAATTGTGATCAACCGTGATGGGGGTGAGAAAG





GTCGCTTGGTTAAACAACTACGCACAACCTACTTGAATGACCTAGATAC





TCATGAGCCACTGGTGACATTCGTAAATACTTATGGATTCATCTACGAA





CAGGATCGGGGAAATACCATTGTCGGAGAGGATCAACATGGGAAGAAAA





GAGAGGCTGTGACTGCTGCAATGGTTACCCTTGGATGTGGGCCTAATCT





ACCATCATTAGGGAATGTCCTGGGACAACTGAGTGAATTCCAGGTCATT





GTTAGGAAGACATCCAGCAAAGCGGAAGAGATGGTCTTTGAAATTGTTA





AGTATCCGAGAATATTTCGGGGTCATACATTAATCCAGAAAGGACTAGT





CTGTGTCTCCGCAGAAAAATTTGTTAAGTCACCAGGGAAAGTACAATCT





GGAATGGACTATCTCTTCATTCCGACATTTCTGTCAGTGACTTACTGTC





CAGCTGCAATCAAATTTCAGGTACCTGGCCCCATGTTGAAAATGAGATC





AAGATACACTCAGAGCTTACAACTTGAACTAATGATAAGAATCCTGTGT





AAGCCCGATTCGCCACTTATGAAGGTCCATATCCCTGACAAGGAAGGAA





GAGGATGTCTTGTATCAGTATGGTTGCATGTATGCAATATCTTCAAATC





AGGAAACAAGAATGGCAGTGAGTGGCAGGAATACTGGATGAGAAAGTGT





GCTAACATGCAACTTGAAGTGTCGATTGCAGATATGTGGGGACCAACTA





TCATAATTCATGCCAGAGGTCACATTCCCAAAAGTGCTAAGTTGTTTTT





TGGAAAGGGTGGATGGAGCTGCCATCCACTTCACGAAGTTGTTCCAAGT





GTCACTAAAACACTATGGTCCGTGGGCTGTGAGATTACAAAGGCGAAGG





CAATAATACAAGAGAGTAGCATCTCTCTTCTCGTGGAGACTACTGACAT





CATAAGTCCAAAAGTCAAAATTTCATCTAAGCATCGCCGCTTTGGGAAA





TCAAATTGGGGTCTGTTCAAGAAAACCAAATCACTGCCCAACCTGACGG





AGCTGGAATGACTGACCCCCAATCGAGACTACACCACCTCAAACTATAG





GTGGGTGGTACCTCAGTGATTAATCTCGTAAGCACTGATCGTAGGCTAC





AACACACTAATATTATCCAGATTAGAGAGCTTAATTAGCTCTGTATTAA





TAATAACACTACTATTCCAATAACTGGAATCACCAGCTTGATTTATCTC





CAAAATGATTCAAAGAAAACAAATCATATTAAGACTATCCTAAGCACGA





ACCCATATCGTCCTTCAAATCATGGGTACTATAATTCAATTTCTGGTGG





TCTCCTGTCTATTGGCAGGAGCAGGCAGTCTTGATCCAGCAGCCCTCAT





GCAAATCGGTGTCATTCCAACAAATGTCCGGCAACTTATGTATTATACT





GAGGCCTCATCAGCATTCATTGTTGTGAAGTTAATGCCTACAATTGACT





CGCCGATTAGTGGATGTAATATAACATCAATTTCAAGCTATAATGCAAC





AGTGACAAAACTCCTACAGCCGATCGGTGAGAATTTGGAGACGATTAGG





AACCAGTTGATTCCAACTCGGAGGAGACGCCGGTTTGCAGGGGTGGTGA





TTGGATTAGCTGCATTAGGAGTAGCTACTGCCGCACAGGTCACTGCCGC





AGTAGCACTAGTAAAGGCAAATGAAAATGCTGCGGCTATACTCAATCTC





AAAAATGCAATCCAAAAAACAAATGCAGCAGTTGCAGATGTGGTCCAGG





CCACACAATCACTAGGAACaGCAGTTCAAGCAGTTCAAGATCACATAAA





CAGTGTGGTAAGTCCAGCAATTACAGCAGCCAATTGTAAAGCCCAAGAT





GCTATCATTGGCTCAATCCTCAATCTCTATTTGACCGAGTTGACAACTA





TCTTCCACAATCAAATTACAAACCCTGCATTGAGTCCTATTACAATTCA





AGCTTTAAGGATCCTACTAGGGAGTACCTTGCCGACTGTGGTCGAAAAA





TCTTTCAATACCCAGATAAGTGCGGCTGAGCTTCTCTCATCAGGGTTAT





TGACAGGCCAGATTGTGGGATTAGATTTGACCTATATGCAGATGGTCAT





AAAAATTGAGCTGCCAACTTTAACTGTACAACCTGCAACCCAGATCATA





GATCTGGCCACCATTTCTGCATTCATTAACAATCAAGAAGTCATGGCCC





AATTACCAACACGTGTTATTGTGACTGGCAGCTTGATCCAAGCCTATCC





CGCATCGCAATGCACTATTACACCCAACACTGTGTACTGTAGGTATAAT





GATGCCCAAGTACTCTCAGATGATACGATGGCTTGCCTCCAAGGTAACT





TGACAAGATGCACCTTCTCTCCAGTGGTTGGGAGCTTTCTCACTCGATT





CGTGCTGTTCGATGGAATAGTTTATGCAAATTGCAGGTCGATGTTGTGC





AAGTGCATGCAGCCTGCTGCTGTGATCCTACAGCCGAGTTCATCCCCTG





TAACTGTCATTGACATGTACAAATGTGTGAGTCTGCAGCTTGACAATCT





CAGATTCACCATCACTCAATTGGCCAATGTAACCTACAATAGCACCATC





AAGCTTGAAACATCCCAGATCTTGCCTATTGATCCGTTGGATATATCCC





AGAATCTAGCTGCGGTGAATAAGAGTCTAAGTGATGCACTACAACACTT





AGCACAAAGTGACACATACCTTTCTGCAATCACATCAGCTACGACTACA





AGTGTATTATCCATAATAGCAATCTGTCTTGGATCGTTAGGTTTAATAT





TAATAATCTTGCTCAGTGTAGTTGTGTGGAAGTTATTGACCATTGTCGC





TGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAATTCAGCATTC





CACCACTCACGATCTGATCTCAGTGAGAAAAATCAACCTGCAACTCTTG





GAACAAGATAAGACAGTCATCCATTAGTAATTTTTAAGAAAAAAACGAT





AGGACCGAAACTAGTATTGAAAGAACCGTCTCGGTCAATCTAGGTAATC





GAGCTGcTACCGTCTCGGAAAGCTCAAATCATGCTGCCTGATCCGGAAG





ATCCGGAAAGCAAAAAAGCTACAAGGAGAACAGGAAACCTAATTATCTG





CTTCCTATTCATCTTCTTTCCGTTTGTAAACTTCATTGTTCCAACTCTA





AGACACTTGCTGTCCTAACACCTGCTATAGGCTATCCACTGCATCATCT





CTTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCC





GGTGCCAACAACACAATCCACAATCTACAGTCGACGCGGCCGCCACCat





gttcgtcttcctggtcctgctgcctctggtctcctcacagtgcgtcaat





ctgATCactcggactcagTCCtatactaatagcttcaccagaggcgtgt





actatcctgacaaggtgtttagaagctccgtgctgcactctacacagga





tctgtttctgccattctttagcaacgtgacctggttccacgccatccac





gtgagcggcaccaatggcacaaagcggttcgacaatcccgtgctgcctt





ttaacgatggcgtgtacttcgcctctaccgagaagagcaacatcatcag





aggctggatctttggcaccacactggactccaagacacagtctctgctg





atcgtgaacaatgccaccaacgtggtcatcaaggtgtgcgagttccagt





tttgtaatgatcccttcctgGACgtgtactatcacaagaacaataagag





ctggatggagtccgagtttagagtgtattctagcgccaacaactgcaca





tttgagtacgtgagccagcctttcctgatggacctggagggcaagcagg





gcaatttcaagaacctgagggagttcgtgtttaagaatatcgacggcta





cttcaaaatctactctaagcacacccccatcaacctgGGCcgcgacctg





cctcagggcttcagcgccctggagcccctggtggatctgcctatcggca





tcaacatcacccggtttcagacactgctggccctgcacagaagctacct





gacacccggcgactcctctagcggatggaccgccggcgctgccgcctac





tatgtgggctacctccagccccggaccttcctgctgaagtacaacgaga





atggcaccatcacagacgcagtggattgcgccctggaccccctgagcga





gacaaagtgtacactgaagtcctttaccgtggagaagggcatctatcag





acatccaatttcagggtgcagccaaccgagtctatcgtgcgctttccta





atatcacaaacctgtgcccatttGACgaggtgttcaacgcaacccgctt





cgccagcgtgtacgcctggaataggaagcggatcagcaactgcgtggcc





gactatagcgtgctgtacaacCTGgccCCCttcTTCGCCtttaagtgct





atggcgtgtcccccacaaagctgaatgacctgtgctttaccaacgtcta





cgccgattctttcgtgatcaggggcAACgaggtgTCCcagatcgccccc





ggccagacaggcAATatcgcagactacaattataagctgccagacgatt





tcaccggctgcgtgatcgcctggaacagcaacAAGctggattccaaagt





gggcggcaactacaattatctgtaccggctgtttagaaagagcaatctg





aagcccttcgagagggacatctctacagaaatctaccaggccggcAATA





AGccttgcaatggcgtgGCCggctttaactgttatttcccactcCGCtc





ctacggcttcCGCcccacaTATggcgtgggcCACcagccttaccgcgtg





gtggtgctgagctttgagctgctgcacgccccagcaacagtgtgcggcc





ccaagaagtccaccaatctggtgaagaacaagtgcgtgaacttcaactt





caacggcctgaccggcacaggcgtgctgaccgagtccaacaagaagttc





ctgccatttcagcagttcggcagggacatcgcagataccacagacgccg





tgcgcgacccacagaccctggagatcctggacatcacaccctgctcttt





cggcggcgtgagcgtgatcacacccggcaccaatacaagcaaccaggtg





gccgtgctgtatcagGGCgtgaattgtaccgaggtgcccgtggctatcc





acgccgatcagctgaccccaacatggcgggtgtacagcaccggctccaa





cgtcttccagacaagagccggatgcctgatcggagcagagTACgtgaac





aattcctatgagtgcgacatcccaatcggcgccggcatctgtgcctctt





accagacccagacaAAGtctCACagaagagcccggagcgtggcctccca





gtctatcatcgcctataccatgtccctgggcgccgagaacagcgtggcc





tactctaacaatagcatcgccatcccaaccaacttcacaatctctgtga





ccacagagatcctgcccgtgtccatgaccaagacatctgtggactgcac





aatgtatatctgtggcgattctaccgagtgcagcaacctgctgctccag





tacggcagcttttgtacccagctgAAGagagccctgacaggcatcgccg





tggagcaggataagaacacacaggaggtgttcgcccaggtgaagcaaat





ctacaagaccccccctatcaagTACtttggcggcttcaatttttcccag





atcctgcctgatccatccaagccttctaagcggagctttatcgaggacc





tgctgttcaacaaggtgaccctggccgatgccggcttcatcaagcagta





tggcgattgcctgggcgacatcgcagccagggacctgatctgcgcccag





aagtttaatggcctgaccgtgctgccacccctgctgacagatgagatga





tcgcacagtacacaagcgccctgctggccggcaccatcacatccggatg





gaccttcggcgcaggagccgccctccagatcccctttgccatgcagatg





gcctataggttcaacggcatcggcgtgacccagaatgtgctgtacgaga





accagaagctgatcgccaatcagtttaactccgccatcggcaagatcca





ggacagcctgtcctctacagccagcgccctgggcaagctccaggatgtg





gtgaatCACaacgcccaggccctgaataccctggtgaagcagctgagca





gcAAGttcggcgccatctctagcgtgctgaatgacatcctgagccggct





ggacaaggtggaggcagaggtgcagatcgaccggctgatcaccggccgg





ctccagagcctccagacctatgtgacacagcagctgatcagggccgccg





agatcagggccagcgccaatctggcagcaaccaagatgtccgagtgcgt





gctgggccagtctaagagagtggacttttgtggcaagggctatcacctg





atgtccttccctcagtctgccccacacggcgtggtgtttctgcacgtga





cctacgtgcccgcccaggagaagaacttcaccacagcccctgccatctg





ccacgatggcaaggcccactttccaagggagggcgtgttcgtgtccaac





ggcacccactggtttgtgacacagcgcaatttctacgagccccagatca





tcaccacagacaacaccttcgtgagcggcaactgtgacgtggtcatcgg





catcgtgaacaataccgtgtatgatccactccagcccgagctggacagc





tttaaggaggagctggataagtatttcaagaatcacacctcccctgacg





tggatctgggcgacatcagcggcatcaatgcctccgtggtgaacatcca





gaaggagatcgaccgcctgaacgaggtggctaagaatctgaacgagagc





ctgatcgacctccaggagctgggcaagtatgagcagtacatcaagtggc





cctggtacatctggctgggcttcatcgccggcctgatcgccatcgtgat





ggtgaccatcatgctgtgctgtatgacatcctgctgttcttgcctgaag





ggctgctgtagctgtggctcctgctgtAAGTTATTGACCATTGTCGTTG





CTAATCGAAATAGAATGGAGAATTTTGTTTATCATAAATGAGCTAGCCT





CCTGCCATACTTCCTACTCACATCATATCTATTTTAAAGAAAAAATAGG





CCCGAACACTAATCGTGCCGGCAGTGCCACTGCACACACAACACTACAC





ATACAATACACTACAATGGTTGCAGAAGATGCCCCTGTTAGGGGCACTT





GCCGAGTATTATTTCGAACAACAACTTTAATTTTTCTATGCACACTATT





AGCATTAAGCATCTCTATCCTTTATGAGAGTTTAATAACCCAAAAGCAA





ATCATGAGCCAAGCAGGCTCAACTGGATCTAATTCTAGATTAGGAAGTA





TCACTGATCTTCTTAATAATATTCTCTCTGTCGCAAATCAGATTATATA





TAACTCTGCAGTCGCTCTACCTCTACAATTGGACACTCTTGAATCAACA





CTCCTTACAGCCATTAAGTCTCTTCAAACAAGTGACAAGCTAGAACAGA





ACTGCTCGTGGGGTGCTGCACTGATTAATGATAATAGATACATTAATGG





CATCAATCAGTTCTATTTCTCAATTGCTGAGGGTCGCAAGCTGACACTT





GGCCCACTTCTTAATATACCTAGTTTCATTCCAACTGCCACGACACCAG





AGGGCTGCACCAGGATCCCATCATTCTCGCTCACCAAGACACACTGGTG





TTATACACACAATGTTATCCTGAATGGATGCCAGGATCATGTATCCTCA





AATCAATTTGTTTCCATGGGAATCATTGAACCCACTTCTGCCGGGTTTC





CATCCTTTCGAACCCTAAAGACTCTATATCTCAGCGATGGGGTCAATCG





TAAGAGCTGCTCTATCAGTACAGTTCCGGGGGGTTGTATGATGTACTGT





TTCGTCTCTACTCAACCAGAGAGGGATGACTACTTTTCTACCGCTCCTC





CAGAACAACGAATTATTATAATGTACTATAATGATACAATCGTGGAGCG





CATAATTAATCCACCCGGGGTACTAGATGTATGGGCAACATTGAACCCA





GGAACAGGAAGCGGGGTATATTATTTAGGTTGGGTACTCTTTCCAATAT





ATGGCGGCGTGATTAAAGATACGAGTTTATGGAATAATCAAGCAAATAA





ATACTTTATCCCCCAGATGGTTGCTGCTCTCTGCTCACAAAACCAGGCA





ACTCAAGTCCAAAATGCTAAGTCATCATACTATAGCAGCTGGTTTGGCA





ATCGAATGATTCAGTCTGGGATCCTGGCATGTCCTCTTCAACAGGATCT





AACCAATGAGTGTTTAGTTCTGCCCTTTTCTAATGATCAGGTGCTTATG





GGTGCTGAAGGGAGATTATACATGTATGGTGACTCGGTGTATTACTACC





AAAGAAGCAATAGTTGGTGGCCTATGACCATGCTGTATAAGGTAACCAT





AACATTCACTAATGGTCAGCCATCTGCTATATCAGCTCAGAATGTGCCC





ACACAGCAGGTCCCTAGACCTGGGACAGGAAGCTGCTCTGCAACAAATA





GATGTCCCGGTTTTTGCTTGAAAGGAGTGTATGCTGATGCCTGGTTACT





GACCAACCCTTCGTCTACCAGTACATTTGGATCAGAAGCAACCTTCACT





GGTTCTTATCTCAACGCAGCAACTCAGCGTATCAATCCGACGATGTATA





TCGCGAACAACACACAGATCATAAGCTCACAGCAATTTGGATCAAGCGG





TCAAGAAGCAGCATATGGCCACACAACTTGTTTTAGGGACACAGGCTCT





GTTATGGTATACTGTATCTATATTATTGAATTGTCCTCATCTCTCTTAG





GACAATTTCAGATTGTCCCATTTATCCGTCAGGTGACACTATCCTAAAG





GCAGAAGCCTCCAGGTCTGACCCAGCCAATCAAAGCATTATACCAGACC





ATGGAATGCATACCAAACATTATTGACACTAATGACACACAAAATTGGT





TTTAAGAAAAACCAAGAGAACAATAGGCCAGAATGGCTGGGTCTCGGGA





GATATTACTCCCTGAAGTCCATCTCAATTCACCAATTGTAAAGCATAAG





CTATACTATTACATTCTACTTGGAAACCTCCCAAATGAGATCGACATTG





ACGATTTAGGTCCATTACATAATCAAAATTGGAATCAAATAGCACATGA





AGAGTCTAACTTAGCCCAACGCTTGGTAAATGTAAGAAATTTTCTAATT





ACCCACATCCCTGATCTTAGAAAGGGCCATTGGCAAGAGTATGTCAATG





TAATACTGTGGCCGCGAATTCTTCCCTTGATCCCGGATTTTAAAATCAA





TGACCAATTGCCTCTACTCAAAAATTGGGACAAGTTAGTTAAAGAATCA





TGTTCAGTAATCAATGCGGGTACTTCCCAGTGCATTCAGAATCTCAGCT





ATGGACTGACAGGTCGTGGGAACCTCTTTACACGATCACGTGAACTCTC





TGGTGACCGCAGGGATATTGATCTTAAGACGGTTGTGGCAGCATGGCAT





GACTCAGACTGGAAAAGAATAAGTGATTTTTGGATTATGATCAAATTCC





AGATGAGACAATTAATTGTTAGGCAAACAGATCATAATGATCCTGATTT





AATCACGTATATCGAAAATAGAGAAGGCATAATCATCATAACCCCTGAA





CTGGTAGCATTATTTAACACTGAGAATCATACACTAACATACATGACCT





TTGAAATTGTACTGATGGTTTCAGATATGTACGAAGGTCGTCACAACAT





TTTATCACTATGCACAGTTAGCACTTACCTGAATCCTCTGAAGAAAAGA





ATAACATATTTATTGAGCCTTGTAGATAACTTAGCTTTTCAGATAGGTG





ATGCTGTATATAACATAATTGCTTTGCTAGAATCCTTTGTATATGCACA





GTTGCAAATGTCAGATCCCATCCCAGAACTCAGAGGACAATTCCATGCA





TTCGTATGTTCTGAGATTCTTGATGCACTAAGGGGAACTAATAGTTTCA





CCCAGGATGAATCAAGAACTGTGACAACCAATTTGATATCCCCATTCCA





AGATCTGACCCCAGATCTTACGGCTGAATTGCTCTGTATAATGAGGCTT





TGGGGACACCCCATGCTCACCGCCAGTCAAGCTGCGGGAAAGGTACGCG





AGTCCATGTGTGCTGGAAAAGTATTAGACTTTCCCACCATTATGAAAAC





ACTAGCCTTTTTCCATACTATTCTGATCAATGGATACAGGAGGAAGCAT





CATGGAGTATGGCCACCCTTAAACTTACCGGGTAATGCTTCAAAGGGTC





TCACGGAACTTATGAATGACAATACTGAGATAAGCTATGAATTCACACT





TAAGCATTGGAAGGAAATCTCTCTTATAAAATTCAAGAAATGTTTTGAT





GCAGACGCAGGTGAGGAACTCAGTATATTTATGAAAGATAAAGCAATTA





GTGCCCCAAAACAAGATTGGATGAGTGTGTTTAGAAGAAGCCTAATCAA





ACAGCGCCATCAGCATCATCAGGTCCCCCTACCAAATCCATTCAATCGA





CGGCTATTGCTAAACTTTCTCGGAGATGACAAATTCGACCCGAATGTGG





AGCTACAGTATGTAACATCAGGTGAGTATCTACATGATGACACGTTTTG





TGCATCATATTCACTAAAAGAGAAGGAAATTAAACCTGATGGTCGAATT





TTTGCAAAGTTGACTAAGAGAATGAGATCATGTCAAGTTATAGCAGAAT





CTCTTTTAGCGAACCATGCTGGGAAGTTAATGAAAGAGAATGGTGTTGT





GATGAATCAGCTATCATTAACAAAATCACTATTAACAATGAGTCAGATT





GGAATAATATCCGAGAAAGCTAGAAAATCGACTCGAGATAACATAAATC





AACCTGGTTTCCAGAATATCCAGAGAAATAAATCACATCACTCCAAGCA





AGTCAATCAGCGAGATCCAAGTGATGACTTTGAATTGGCAGCATCTTTT





TTAACTACTGATCTCAAAAAATATTGTTTACAATGGAGGTACCAGACAA





TTATCCCATTTGCTCAATCATTAAACAGAATGTATGGTTATCCTCATCT





CTTTGAGTGGATTCACTTACGGCTAATGCGTAGTACACTTTACGTGGGG





GATCCCTTCAACCCACCAGCAGATACCAGTCAATTTGATCTAGATAAAG





TAATTAATGGAGATATCTTCATTGTATCACCCAGAGGTGGAATTGAAGG





GCTATGTCAAAAGGCTTGGACAATGATATCTATCTCTGTGATAATTCTA





TCTGCCACAGAGTCTGGCACACGAGTAATGAGTATGGTGCAGGGAGATA





ATCAAGCAATTGCTGTCACCACACGAGTACCAAGGAGCCTGCCGACTCT





TGAGAAAAAGACTATTGCTTTTAGATCTTGTAATCTATTCTTTGAGAGG





TTAAAATGTAATAATTTTGGATTAGGTCACCATTTGAAAGAACAAGAGA





CTATCATTAGTTCTCACTTCTTTGTTTATAGCAAGAGAATATTCTATCA





GGGGAGGATTCTAACGCAAGCCTTAAAAAATGCTAGTAAGCTCTGCTTG





ACAGCTGATGTCCTAGGAGAATGTACCCAATCATCATGTTCTAATCTTG





CAACTACTGTCATGAGGTTAACTGAGAATGGTGTTGAAAAAGATATCTG





TTTCTACTTGAATATCTATATGACCATCAAACAGCTCTCCTATGATATC





ATCTTCCCTCAAGTGTCAATTCCTGGAGATCAGATCACATTAGAATACA





TAAATAATCCACACCTGGTATCACGATTGGCTCTTCTGCCATCCCAGCT





AGGAGGTCTAAACTACCTGTCATGCAGTAGGCTGTTCAATCGAAACATA





GGCGACCCGGTGGTTTCCGCAGTTGCAGATCTTAAGAGATTAATTAAAT





CAGGATGTATGGATTACTGGATCCTTTATAACTTATTAGGGAGAAAACC





GGGAAACGGCTCATGGGCTACTTTAGCAGCTGACCCGTACTCAATCAAT





ATAGAGTATCAATACCCCCCAACTACAGCTCTTAAGAGGCACACCCAAC





AAGCTCTGATGGAACTCAGTACGAATCCAATGTTACGTGGCATATTCTC





TGACAATGCACAGGCAGAAGAAAATAATCTTGCTAGATTTCTCCTGGAT





AGGGAGGTGATCTTTCCGCGTGTAGCTCACATCATCATTGAGCAAACCA





GTGTCGGGAGGAGAAAACAGATTCAAGGATATTTGGATTCAACTAGATC





GATAATGAGTAAATCACTAGAAATTAAGCCCTTGTCCAATAGGAAGCTT





AATGAAATACTGGATTACAACATCAATTACCTAGCTTACAATTTGGCAT





TACTCAAGAATGCTATTGAACCTCCGACTTATTTGAAAGCAATGACTCT





TGAAACATGTAGCATCGACATTGCAAGGAGCCTCCGGAAGCTCTCCTGG





GCCCCACTCTTGGGTGGGAGAAATCTTGAAGGATTAGAGACGCCAGATC





CCATTGAAATTACTGCAGGAGCATTAATTGTTGGATCGGGCTACTGTGA





ACAGTGTGCTGCAGGAGACAATCGATTCACATGGTTTTTCTTGCCATCT





GGTATCGAGATAGGAGGGGATCCCCGTGATAATCCTCCTATCCGTGTAC





CGTACATTGGCTCCAGGACTGATGAGAGGAGGGTAGCCTCAATGGCATA





CATCAGGGGTGCCTCGAGTAGCCTAAAAGCAGTTCTTAGACTGGCGGGA





GTGTACATCTGGGCATTCGGAGATACTCTGGAGAATTGGATAGATGCAC





TGGATTTGTCTCACACTAGAGTTAACATCACACTTGAACAGCTGCAATC





CCTCACCCCACTTCCAACCTCTGCCAATCTAACCCATCGGTTGGATGAT





GGCACAACTACCCTAAAGTTTACTCCTGCGAGCTCTTACACCTTTTCAA





GTTTCACTCATATATCAAATGATGAGCAATACCTGACAATTAATGACAA





AACTGCAGATTCAAATATAATCTACCAACAGTTAATGATCACTGGACTC





GGAATTTTAGAAACATGGAATAATCCCCCAATCAATAGAACATTCGAAG





AATCTACCCTACATTTGCACACTGGTGCATCATGTTGTGTCCGACCTGT





GGACTCCTGCATCATCTCAGAAGCATTAACAGTCAAGCCACATATTACA





GTACCGTACAGCAATAAATTTGTATTTGATGAAGACCCGCTATCTGAAT





ATGAGACTGCAAAACTGGAATCGTTATCATTTCAAGCCCAATTAGGCAA





CATTGATGCTGTAGATATGACAGGTAAATTAACATTATTGTCCCAATTC





ACTGCAAGGCAGATTATTAATGCAATCACTGGACTCGATGAGTCTGTCT





CTCTTACTAATGATGCCATTGTTGCATCAGACTATGTCTCCAATTGGAT





TAGTGAATGCATGTATACCAAATTAGATGAATTATTTATGTATTGTGGG





TGGGAACTACTATTGGAACTATCCTATCAAATGTATTATCTGAGGGTAG





TTGGGTGGAGTAATATAGTGGATTATTCTTACATGATCTTGAGAAGAAT





CCCGGGTGCAGCATTAAACAATCTGGCATCTACATTAAGTCATCCAAAA





CTTTTCCGACGAGCTATCAACCTAGATATAGTTGCCCCCTTAAATGCTC





CTCATTTTGCATCTCTGGACTACATCAAGATGAGTGTGGATGCAATACT





CTGGGGCTGTAAAAGAGTCATCAATGTGCTCTCCAATGGAGGGGACTTA





GAATTAGTTGTGACATCTGAAGATAGCCTTATTCTCAGTGACCGATCCA





TGAATCTCATTGCAAGGAAATTAACTTTATTATCACTGATTCACCATAA





TGGTTTGGAACTACCAAAGATTAAGGGGTTCTCTCCTGATGAGAAGTGT





TTCGCTTTGACAGAATTTTTGAGGAAAGTGGTGAACTCAGGGTTGAGTT





CAATAGAGAACCTATCAAATTTTATGTACAATGTGGAGAACCCACGGCT





TGCAGCATTCGCCAGCAACAATTACTACCTGACCAGAAAATTATTGAAT





TCAATACGAGATACTGAGTCGGGTCAAGTAGCAGTCACCTCATATTATG





AATCATTAGAATATATTGATAGTCTTAAGCTAACCCCACATGTGCCTGG





TACCTCATGCATTGAGGATGATAGTCTATGTACAAATGATTACATAATC





TGGATCATAGAGTCTAATGCAAACTTGGAGAAGTATCCAATTCCAAATA





GCCCTGAGGATGATTCCAATTTCCATAACTTTAAGTTGAATGCTCCATC





GCACCATACCTTACGCCCATTAGGGTTGTCATCAACTGCTTGGTATAAG





GGTATAAGCTGTTGCAGGTACCTTGAGCGATTAAAGCTACCACAAGGTG





ATCATTTATATATTGCAGAAGGTAGTGGTGCCAGTATGACAATCATAGA





ATACCTATTCCCAGGAAGAAAGATATATTACAATTCTTTATTTAGTAGT





GGTGACAATCCCCCACAAAGAAATTATGCACCAATGCCTACTCAGTTCA





TTGAGAGTGTCCCATACAAGCTCTGGCAAGCACACACAGATCAATATCC





CGAGATTTTTGAGGACTTCATCCCTCTATGGAACGGAAATGCCGCCATG





ACTGACATAGGAATGACAGCTTGTGTAGAATTCATCATCAATCGAGTCG





GCCCAAGGACTTGCAGTTTAGTACATGTAGATTTGGAATCAAGTGCAAG





CTTAAATCAACAATGCCTGTCAAAGCCGATAATTAATGCTATCATCACT





GCTACAACTGTTTTGTGCCCTCATGGGGTGCTTATTCTGAAATATAGTT





GGTTGCCATTTACTAGATTTAGTACTTTGATCACTTTCTTATGGTGCTA





CTTTGAGAGAATCACTGTTCTTAGGAGCACATATTCTGGTCCAGCTAAT





CATGAGGTTTATTTAATTTGTATCCTTGCCAACAACTTTGCATTCCAGA





CTGTCTCGCAGGCAACAGGAATGGCGATGACTTTAACCGATCAAGGGTT





TACTTTGATATCACCTGAAAGAATAAATCAGTATTGGGATGGTCACTTG





AAGCAAGAACGTATCGTAGCAGAAGCAATTGATAAGGTGGTTCTAGGAG





AAGATGCTCTATTCAATTCGAGTGATAATGAATTAATTCTCAAATGTGG





AGGGACACCAAATGCACGGAATCTTATCGATATCGAGCCAGTCGCAACT





TTCATAGAATTTGAACAACTGATCTGCACAATGTTGACAACCCACTTGA





AGGAAATAATTGATATAACAAGGTCTGGAACCCAGGATTATGAAAGTTT





ATTACTCACTCCTTACAATTTAGGTCTTCTTGGTAAAATCAGTACGATA





GTGAGATTATTAACAGAAAGGATTCTAAATCATACTATCAGGAATTGGT





TGATCCTCCCACCTTCGCTCCGGATGATCGTGAAGCAGGACTTGGAATT





CGGCATATTCAGGATTACTTCCATCCTCAATTCTGATCGGTTCCTGAAG





CTTTCTCCAAATAGGAAATACTTGATTACACAATTAACTGCAGGCTACA





TTAGGAAATTGATTGAGGGGGATTGTAATATCGATCTAACCAGACCTAT





CCAAAAACAAATCTGGAAAGCATTAGGTTGTGTAGTCTATTGTCACGAT





CCAGTAGATCAAAGGGAATCAACAGAGTTTATTGATATAAATATTAATG





AAGAAATAGACCGCGGGATCGATGGCGAGGAAATCTAAATATATCAAGA





ATCAGAATTAGTTTAAGAAAAAAGAAGAGGATTAATCTTGGTTTTCCCC





TTGGT.






19. CVL108


The nucleic acid sequence for CVL108 is:










(SEQ ID NO: 78)



ACCAGGGGGAAAACGAAGTGGTGACTCAAATCATCGAAGACCCTCGAGATTACATAGGTCCGGAACC






TATGGCCTTCGTGACCGACCTCGAGTCAGAGTAGTTCAATAAGGACCTATCAAGTTTGGGCAATTTTTC





GTCCCCGACACAAAAATGTCATCCGTGCTTAAAGCATATGAGCGATTCACACTCACTCAAGAACTGCA





AGATCAGAGTGAGGAAGGTACAATCCCACCTACAACACTAAAACCGGTAATCAGGGTATTTATACTAA





CCTCTAATAACCCAGAGCTAAGATCCCGGCTTCTTCTATTCTGCCTACGGATTGTTCTCAGTAATGGTG





CAAGGGATTCCCATCGCTTTGGAGCATTACTTACAATGTTTTCGCTACCATCAGCCACAATGCTCAATC





ATGTCAAATTAGCTGACCAGTCACCAGAAGCTGATATCGAAAGGGTAGAGATCGATGGCTTTGAGGA





GGGATCATTCCGCTTAATCCCCAATGCTCGTTCAGGTATGAGCCGTGGAGAGATCAATGCCTATGCTG





CACTTGCAGAAGATCTACCTGACACACTAAACCATGCAACACCTTTTGTTGATTCCGAAGTCGAGGGA





ACTGCATGGGATGAGATTGAGACTTTCTTAGATATGTGTTACAGTGTCCTAATGCAGGCATGGATAGT





GACTTGCAAGTGCATGACTGCGCCAGACCAACCTGCTGCTTCTATTGAGAAACGCCTGCAAAAATATC





GTCAGCAAGGCAGGATCAACCCGAGATATCTCCTGCAACCGGAGGCTCGAAGAATAATCCAGAATGT





AATCCGAAAGGGAATGGTGGTCAGACATTTCCTCACCTTTGAACTGCAGCTTGCCCGAGCACAAAGCC





TTGTATCAAATAGGTATTATGCTATGGTAGGGGATGTTGGAAAGTATATAGAGAATTGTGGAATGGGA





GGCTTCTTTTTGACACTAAAATATGCATTAGGAACCAGATGGCCCACACTTGCTTTAGCTGCATTTTCA





GGAGAGCTAACAAAGCTAAAGTCCCTCATGGCATTATACCAGACCCTTGGTGAGCAGGCCCGATATTT





GGCCCTATTGGAGTCACCACATTTGATGGATTTTGCTGCAGCAAACTACCCACTGCTATATAGCTATGC





TATGGGAATAGGCTATGTGTTAGATGTCAACATGAGGAACTACGCTTTCTCCAGATCATACATGAATA





AGACATATTTCCAATTGGGAATGGAAACTGCAAGAAAACAACAGGGTGCAGTTGACATGAGGATGGC





AGAAGATCTCGGTCTAACTCAAGCCGAACGCACCGAGATGGCAAATACACTTGCCAAATTGACCACA





GCAAATCGAGGGGCAGACACCAGGGGAGGAGTCAACCCGTTCTCATCTATCACTGGGACAACTCAGG





TGCCCGCTGCAGCAACAGGTGACACATTCGAGAGTTACATGGCAGCGGATCGACTGAGGCAGAGATA





TGCTGATGCAGGCACCCACGATGATGAGATGCCACCATTGGAAGAGGAGGAAGAGGACGACACATCT





GCAGGTCCACGCACTGGACTAACTCTTGAACAAGTGGCCTTGGACATCCAGAACGCAGCAGTTGGAGC





TCCCATCCATACAGATGACCTGAATGCCGCACTGGGTGATCTTGACATCTAGACAATTCAGATCCCAA





TCTTAAATCGACACACCTAATTGACCAGTTAGATGGAACTACAGTGGATTCCATAAGGTTCCTGCCTAC





CATCGGCTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCCGATGCCAATAACA





CAATCCACAATCTACAATGGATCCCACTGATCTGAGCTTCTCCCCAGATGAGATCAATAAGCTCATAG





AGACAGGCCTGAATACTGTGGAGTATTTTACTTCCCAACAAGTCACAGGAACATCCTCTCTTGGAAAG





AATACAATACCACCAGGGGTCACAGGACTACTAACCAATGCTGCAGAGGCAAAGATCCAAGAGTCAA





CCAACCATCAGAAGGGTTCAGTTGGTGGGGGCGCAAAACCAAAGAAACCGCGACCAAAAATTGCCAT





TGTGCCAGCAGATGACAAAACGGTGCCCGGAAAGCCGATCCCAAACCCTCTATTAGGTCTGGACTCCA





CCCCGAGCACCCAAACTGTGCTTGATCTAAGTGGGAAAACATTACCATCAGGATCCTATAAGGGGGTT





AAACTTGCGAAATTTGGAAAAGAAAATCTGATGACACGGTTCATCGAGGAACCCAGAGAGAATCCTA





TCGCAACCAATTCCCCCATCGATTTTAAGAGGGGCAGGGATACCGGCGGGTTCCATAGAAGGGAGTAC





TCAATCGGATGGGTGGGAGATGAAGTCAAGGTCACTGAGTGGTGCAATCCATCCTGTTCTCCAATCAC





CGCTGCAGCAAGGCGATTTGAATGCACTTGTCACCAGTGTCCAGTCACTTGCTCTGAATGTGAACGAG





ATACTTAATACAGTGAGAAATTTGGACTCTCGGATGAATCAACTGGAGACAAAAGTAGATCGCATTCT





CTCATCTCAGTCTCTAATCCAGACCATCAAGAATGACATAGTTGGACTTAAAGCAGGGATGGCTACTT





TAGAAGGAATGATTACAACTGTGAAAATCATGGACCCGGGAGTTCCCAGTAATGTTACTGTGGAAGAT





GTACGCAAGAAACTAAGTAACCATGCTGTTGTTGTGCCAGAATCATTCAATGATAGTTTCTTGACTCAA





TCTGAAGATGTAATTTCACTTGATGAGTTGGCTCGACCAACTGCAACAAGTGTTAAGAAGATTGTCAG





GAAGGTTCCTCCTCAGAAGGATCTGACTGGATTGAAGATCACACTAGAGCAATTGGCAAAGGATTGCA





TCAGCAAACCGAAGATGAGGGAAGAGTATCTCCTCAAAATCAACCAGGCTTCCAGTGAGGCTCAGCT





AATTGACCTCAAGAAAGCAATCATCCGCAGTGCAATTTGATCAAGAAACACCCAATTACACTACACTG





GTATGACACTGTACTAACCCTGAGGGTTTTAGAAAAAACGATTAACGATAAATAAGCCCGAACACTAC





ACACCACCCGAGGCAGCCATGCCATCCATCAGCATCCCCGCAGACCCCACCAATCCACGTCAATCAAT





AAAAGCGTTCCCAATTGTGATCAACCGTGATGGGGGTGAGAAAGGTCGCTTGGTTAAACAACTACGCA





CAACCTACTTGAATGACCTAGATACTCATGAGCCACTGGTGACATTCGTAAATACTTATGGATTCATCT





ACGAACAGGATCGGGGAAATACCATTGTCGGAGAGGATCAACATGGGAAGAAAAGAGAGGCTGTGA





CTGCTGCAATGGTTACCCTTGGATGTGGGCCTAATCTACCATCATTAGGGAATGTCCTGGGACAACTG





AGTGAATTCCAGGTCATTGTTAGGAAGACATCCAGCAAAGCGGAAGAGATGGTCTTTGAAATTGTTAA





GTATCCGAGAATATTTCGGGGTCATACATTAATCCAGAAAGGACTAGTCTGTGTCTCCGCAGAAAAAT





TTGTTAAGTCACCAGGGAAAGTACAATCTGGAATGGACTATCTCTTCATTCCGACATTTCTGTCAGTGA





CTTACTGTCCAGCTGCAATCAAATTTCAGGTACCTGGCCCCATGTTGAAAATGAGATCAAGATACACT





CAGAGCTTACAACTTGAACTAATGATAAGAATCCTGTGTAAGCCCGATTCGCCACTTATGAAGGTCCA





TATCCCTGACAAGGAAGGAAGAGGATGTCTTGTATCAGTATGGTTGCATGTATGCAATATCTTCAAAT





CAGGAAACAAGAATGGCAGTGAGTGGCAGGAATACTGGATGAGAAAGTGTGCTAACATGCAACTTGA





AGTGTCGATTGCAGATATGTGGGGACCAACTATCATAATTCATGCCAGAGGTCACATTCCCAAAAGTG





CTAAGTTGTTTTTTGGAAAGGGTGGATGGAGCTGCCATCCACTTCACGAAGTTGTTCCAAGTGTCACTA





AAACACTATGGTCCGTGGGCTGTGAGATTACAAAGGCGAAGGCAATAATACAAGAGAGTAGCATCTC





TCTTCTCGTGGAGACTACTGACATCATAAGTCCAAAAGTCAAAATTTCATCTAAGCATCGCCGCTTTGG





GAAATCAAATTGGGGTCTGTTCAAGAAAACCAAATCACTGCCCAACCTGACGGAGCTGGAATGACTG





ACCCCCAATCGAGACTACACCACCTCAAACTATAGGTGGGTGGTACCTCAGTGATTAATCTCGTAAGC





ACTGATCGTAGGCTACAACACACTAATATTATCCAGATTAGAGAGCTTAATTAGCTCTGTATTAATAAT





AACACTACTATTCCAATAACTGGAATCACCAGCTTGATTTATCTCCAAAATGATTCAAAGAAAACAAA





TCATATTAAGACTATCCTAAGCACGAACCCATATCGTCCTTCAAATCATGGGTACTATAATTCAATTTC





TGGTGGTCTCCTGTCTATTGGCAGGAGCAGGCAGTCTTGATCCAGCAGCCCTCATGCAAATCGGTGTC





ATTCCAACAAATGTCCGGCAACTTATGTATTATACTGAGGCCTCATCAGCATTCATTGTTGTGAAGTTA





ATGCCTACAATTGACTCGCCGATTAGTGGATGTAATATAACATCAATTTCAAGCTATAATGCAACAGT





GACAAAACTCCTACAGCCGATCGGTGAGAATTTGGAGACGATTAGGAACCAGTTGATTCCAACTCGGA





GGAGACGCCGGTTTGCAGGGGTGGTGATTGGATTAGCTGCATTAGGAGTAGCTACTGCCGCACAGGTC





ACTGCCGCAGTAGCACTAGTAAAGGCAAATGAAAATGCTGCGGCTATACTCAATCTCAAAAATGCAAT





CCAAAAAACAAATGCAGCAGTTGCAGATGTGGTCCAGGCCACACAATCACTAGGAACaGCAGTTCAAG





CAGTTCAAGATCACATAAACAGTGTGGTAAGTCCAGCAATTACAGCAGCCAATTGTAAAGCCCAAGAT





GCTATCATTGGCTCAATCCTCAATCTCTATTTGACCGAGTTGACAACTATCTTCCACAATCAAATTACA





AACCCTGCATTGAGTCCTATTACAATTCAAGCTTTAAGGATCCTACTAGGGAGTACCTTGCCGACTGTG





GTCGAAAAATCTTTCAATACCCAGATAAGTGCGGCTGAGCTTCTCTCATCAGGGTTATTGACAGGCCA





GATTGTGGGATTAGATTTGACCTATATGCAGATGGTCATAAAAATTGAGCTGCCAACTTTAACTGTAC





AACCTGCAACCCAGATCATAGATCTGGCCACCATTTCTGCATTCATTAACAATCAAGAAGTCATGGCC





CAATTACCAACACGTGTTATTGTGACTGGCAGCTTGATCCAAGCCTATCCCGCATCGCAATGCACTATT





ACACCCAACACTGTGTACTGTAGGTATAATGATGCCCAAGTACTCTCAGATGATACGATGGCTTGCCT





CCAAGGTAACTTGACAAGATGCACCTTCTCTCCAGTGGTTGGGAGCTTTCTCACTCGATTCGTGCTGTT





CGATGGAATAGTTTATGCAAATTGCAGGTCGATGTTGTGCAAGTGCATGCAGCCTGCTGCTGTGATCCT





ACAGCCGAGTTCATCCCCTGTAACTGTCATTGACATGTACAAATGTGTGAGTCTGCAGCTTGACAATCT





CAGATTCACCATCACTCAATTGGCCAATGTAACCTACAATAGCACCATCAAGCTTGAAACATCCCAGA





TCTTGCCTATTGATCCGTTGGATATATCCCAGAATCTAGCTGCGGTGAATAAGAGTCTAAGTGATGCAC





TACAACACTTAGCACAAAGTGACACATACCTTTCTGCAATCACATCAGCTACGACTACAAGTGTATTA





TCCATAATAGCAATCTGTCTTGGATCGTTAGGTTTAATATTAATAATCTTGCTCAGTGTAGTTGTGTGG





AAGTTATTGACCATTGTCGCTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAATTCAGCATTC





CACCACTCACGATCTGATCTCAGTGAGAAAAATCAACCTGCAACTCTTGGAACAAGATAAGACAGTCA





TCCATTAGTAATTTTTAAGAAAAAAACGATAGGACCGAAACTAGTATTGAAAGAACCGTCTCGGTCAA





TCTAGGTAATCGAGCTGcTACCGTCTCGGAAAGCTCAAATCATGCTGCCTGATCCGGAAGATCCGGAA





AGCAAAAAAGCTACAAGGAGAACAGGAAACCTAATTATCTGCTTCCTATTCATCTTCTTTCCGTTTGTA





AACTTCATTGTTCCAACTCTAAGACACTTGCTGTCCTAACACCTGCTATAGGCTATCCACTGCATCATC





TCTTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCCGGTGCCAACAACACAAT





CCACAATCTACAGTCGACGCGGCCGCCACCatgttcgtcttcctggtcctgctgcctctggtctcctcac





agtgcgtcaatctgATCactcggactcagTCCtatactaatagcttcaccagaggcgtgtactatcctg





acaaggtgtttagaagctccgtgctgcactctacacaggatctgtttctgccattctttagcaacgtg





acctggttccacgccatcagcggcaccaatggcacaaagcggttcgacaatcccgtgctgccttttaacg





atggcgtgtacttcgcctctaccgagaagagcaacatcatcagaggctggatctttggcaccacactg





gactccaagacacagtctctgctgatcgtgaacaatgccaccaacgtggtcatcaaggtgtgcgagttc





cagttttgtaatgatcccttcctgGACgtgtactatcacaagaacaataagagctggatggagtccgagt





ttagagtgtattctagcgccaacaactgcacatttgagtacgtgagccagcctttcctgatggacctg





gagggcaagcagggcaatttcaagaacctgagggagttcgtgtttaagaatatcgacggctacttcaaa





atctactctaagcacacccccatcaacctgGGCcgcgacctgcctcagggcttcagcgccctggagccc





ctggtggatctgcctatcggcatcaacatcacccggtttcagacactgctggccctgcacagaagctacc





tgacacccggcgactcctctagcggatggaccgccggcgctgccgcctactatgtgggctacctccag





ccccggaccttcctgctgaagtacaacgagaatggcaccatcacagacgcagtggattgcgccctggac





cccctgagcgagacaaagtgtacactgaagtcctttaccgtggagaagggcatctatcagacatcca





atttcagggtgcagccaaccgagtctatcgtgcgctttcctaatatcacaaacctgtgcccatttGAC





gaggtgttcaacgcaacccgcttcgccagcgtgtacgcctggaataggaagcggatcagcaactgcgtgg





ccgactatagcgtgctgtacaacCTGgccCCCttcTTCGCCtttaagtgctatggcgtgtcccccaca





aagctgaatgacctgtgctttaccaacgtctacgccgattctttcgtgatcaggggcAACgaggtgTCC





cagatcgcccccggccagacaggcAATatcgcagactacaattataagctgccagacgatttcaccggc





tgcgtgatcgcctggaacagcaacAAGctggattccaaagtgggcggcaactacaattatAGAtaccggc





tgtttagaaagagcaatctgaagcccttcgagagggacatctctacagaaatctaccaggccggcAAT





AAGccttgcaatggcgtgGCCggcGTGaactgttatttcccactcCAGtcctacggcttcCGCcccacaT





ATggcgtgggcCACcagccttaccgcgtggtggtgctgagctttgagctgctgcacgccccagcaacag





tgtgcggccccaagaagtccaccaatctggtgaagaacaagtgcgtgaacttcaacttcaacggcctg





accggcacaggcgtgctgaccgagtccaacaagaagttcctgccatttcagcagttcggcagggacat





cgcagataccacagacgccgtgcgcgacccacagaccctggagatcctggacatcacaccctgctctttc





ggcggcgtgagcgtgatcacacccggcaccaatacaagcaaccaggtggccgtgctgtatcagGGCgt





gaattgtaccgaggtgcccgtggctatccacgccgatcagctgaccccaacatggcgggtgtacagca





ccggctccaacgtcttccagacaagagccggatgcctgatcggagcagagTACgtgaacaattcctatg





agtgcgacatcccaatcggcgccggcatctgtgcctcttaccagacccagacaAAGtctCACagaagag





cccggagcgtggcctcccagtctatcatcgcctataccatgtccctgggcgccgagaacagcgtggccta





ctctaacaatagcatcgccatcccaaccaacttcacaatctctgtgaccacagagatcctgcccgtgtc





catgaccaagacatctgtggactgcacaatgtatatctgtggcgattctaccgagtgcagcaacctgct





gctccagtacggcagcttttgtacccagctgAAGagagccctgacaggcatcgccgtggagcaggat





aagaacacacaggaggtgttcgcccaggtgaagcaaatctacaagaccccccctatcaagTACtttg





gcggcttcaatttttcccagatcctgcctgatccatccaagccttctaagcggagctttatcgaggac





ctgctgttcaacaaggtgaccctggccgatgccggcttcatcaagcagtatggcgattgcctgggcga





catcgcagccagggacctgatctgcgcccagaagtttaatggcctgaccgtgctgccacccctgctg





acagatgagatgatcgcacagtacacaagcgccctgctggccggcaccatcacatccggatggaccttc





ggcgcaggagccgccctccagatcccctttgccatgcagatggcctataggttcaacggcatcggcgtga





cccagaatgtgctgtacgagaaccagaagctgatcgccaatcagtttaactccgccatcggcaagatcc





aggacagcctgtcctctacagccagcgccctgggcaagctccaggatgtggtgaatCACaacgcccagg





ccctgaataccctggtgaagcagctgagcagcAAGttcggcgccatctctagcgtgctgaatgaca





tcctgagccggctggacaaggtggaggcagaggtgcagatcgaccggctgatcaccggccggctccag





agcctccagacctatgtgacacagcagctgatcagggccgccgagatcagggccagcgccaatctgg





cagcaaccaagatgtccgagtgcgtgctgggccagtctaagagagtggacttttgtggcaagggcta





tcacctgatgtccttccctcagtctgccccacacggcgtggtgtttctgcacgtgacctacgtgcccg





cccaggagaagaacttcaccacagcccctgccatctgccacgatggcaaggcccactttccaagggagg





gcgtgttcgtgtccaacggcacccactggtttgtgacacagcgcaatttctacgagccccagatcatcac





cacagacaacaccttcgtgagcggcaactgtgacgtggtcatcggcatcgtgaacaataccgtgtatgat





ccactccagcccgagctggacagctttaaggaggagctggataagtatttcaagaatcacacctccc





ctgacgtggatctgggcgacatcagcggcatcaatgcctccgtggtgaacatccagaaggagatcgac





cgcctgaacgaggtggctaagaatctgaacgagagcctgatcgacctccaggagctgggcaagtatga





gcagtacatcaagtggccctggtacatctggctgggcttcatcgccggcctgatcgccatcgtgatggt





gaccatcatgctgtgctgtatgacatcctgctgttcttgcctgaagggctgctgtagctgtggctcctg





ctgtAAGTTATTGACCATTGTCGTTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAAATGAGCT





AGCCTCCTGCCATACTTCCTACTCACATCATATCTATTTTAAAGAAAAAATAGGCCCGAACACTAATCG





TGCCGGCAGTGCCACTGCACACACAACACTACACATACAATACACTACAATGGTTGCAGAAGATGCCC





CTGTTAGGGGCACTTGCCGAGTATTATTTCGAACAACAACTTTAATTTTTCTATGCACACTATTAGCAT





TAAGCATCTCTATCCTTTATGAGAGTTTAATAACCCAAAAGCAAATCATGAGCCAAGCAGGCTCAACT





GGATCTAATTCTAGATTAGGAAGTATCACTGATCTTCTTAATAATATTCTCTCTGTCGCAAATCAGATT





ATATATAACTCTGCAGTCGCTCTACCTCTACAATTGGACACTCTTGAATCAACACTCCTTACAGCCATT





AAGTCTCTTCAAACAAGTGACAAGCTAGAACAGAACTGCTCGTGGGGTGCTGCACTGATTAATGATAA





TAGATACATTAATGGCATCAATCAGTTCTATTTCTCAATTGCTGAGGGTCGCAAGCTGACACTTGGCCC





ACTTCTTAATATACCTAGTTTCATTCCAACTGCCACGACACCAGAGGGCTGCACCAGGATCCCATCATT





CTCGCTCACCAAGACACACTGGTGTTATACACACAATGTTATCCTGAATGGATGCCAGGATCATGTAT





CCTCAAATCAATTTGTTTCCATGGGAATCATTGAACCCACTTCTGCCGGGTTTCCATCCTTTCGAACCCT





AAAGACTCTATATCTCAGCGATGGGGTCAATCGTAAGAGCTGCTCTATCAGTACAGTTCCGGGGGGTT





GTATGATGTACTGTTTCGTCTCTACTCAACCAGAGAGGGATGACTACTTTTCTACCGCTCCTCCAGAAC





AACGAATTATTATAATGTACTATAATGATACAATCGTGGAGCGCATAATTAATCCACCCGGGGTACTA





GATGTATGGGCAACATTGAACCCAGGAACAGGAAGCGGGGTATATTATTTAGGTTGGGTACTCTTTCC





AATATATGGCGGCGTGATTAAAGATACGAGTTTATGGAATAATCAAGCAAATAAATACTTTATCCCCC





AGATGGTTGCTGCTCTCTGCTCACAAAACCAGGCAACTCAAGTCCAAAATGCTAAGTCATCATACTAT





AGCAGCTGGTTTGGCAATCGAATGATTCAGTCTGGGATCCTGGCATGTCCTCTTCAACAGGATCTAACC





AATGAGTGTTTAGTTCTGCCCTTTTCTAATGATCAGGTGCTTATGGGTGCTGAAGGGAGATTATACATG





TATGGTGACTCGGTGTATTACTACCAAAGAAGCAATAGTTGGTGGCCTATGACCATGCTGTATAAGGT





AACCATAACATTCACTAATGGTCAGCCATCTGCTATATCAGCTCAGAATGTGCCCACACAGCAGGTCC





CTAGACCTGGGACAGGAAGCTGCTCTGCAACAAATAGATGTCCCGGTTTTTGCTTGAAAGGAGTGTAT





GCTGATGCCTGGTTACTGACCAACCCTTCGTCTACCAGTACATTTGGATCAGAAGCAACCTTCACTGGT





TCTTATCTCAACGCAGCAACTCAGCGTATCAATCCGACGATGTATATCGCGAACAACACACAGATCAT





AAGCTCACAGCAATTTGGATCAAGCGGTCAAGAAGCAGCATATGGCCACACAACTTGTTTTAGGGACA





CAGGCTCTGTTATGGTATACTGTATCTATATTATTGAATTGTCCTCATCTCTCTTAGGACAATTTCAGAT





TGTCCCATTTATCCGTCAGGTGACACTATCCTAAAGGCAGAAGCCTCCAGGTCTGACCCAGCCAATCA





AAGCATTATACCAGACCATGGAATGCATACCAAACATTATTGACACTAATGACACACAAAATTGGTTT





TAAGAAAAACCAAGAGAACAATAGGCCAGAATGGCTGGGTCTCGGGAGATATTACTCCCTGAAGTCC





ATCTCAATTCACCAATTGTAAAGCATAAGCTATACTATTACATTCTACTTGGAAACCTCCCAAATGAGA





TCGACATTGACGATTTAGGTCCATTACATAATCAAAATTGGAATCAAATAGCACATGAAGAGTCTAAC





TTAGCCCAACGCTTGGTAAATGTAAGAAATTTTCTAATTACCCACATCCCTGATCTTAGAAAGGGCCAT





TGGCAAGAGTATGTCAATGTAATACTGTGGCCGCGAATTCTTCCCTTGATCCCGGATTTTAAAATCAAT





GACCAATTGCCTCTACTCAAAAATTGGGACAAGTTAGTTAAAGAATCATGTTCAGTAATCAATGCGGG





TACTTCCCAGTGCATTCAGAATCTCAGCTATGGACTGACAGGTCGTGGGAACCTCTTTACACGATCACG





TGAACTCTCTGGTGACCGCAGGGATATTGATCTTAAGACGGTTGTGGCAGCATGGCATGACTCAGACT





GGAAAAGAATAAGTGATTTTTGGATTATGATCAAATTCCAGATGAGACAATTAATTGTTAGGCAAACA





GATCATAATGATCCTGATTTAATCACGTATATCGAAAATAGAGAAGGCATAATCATCATAACCCCTGA





ACTGGTAGCATTATTTAACACTGAGAATCATACACTAACATACATGACCTTTGAAATTGTACTGATGGT





TTCAGATATGTACGAAGGTCGTCACAACATTTTATCACTATGCACAGTTAGCACTTACCTGAATCCTCT





GAAGAAAAGAATAACATATTTATTGAGCCTTGTAGATAACTTAGCTTTTCAGATAGGTGATGCTGTAT





ATAACATAATTGCTTTGCTAGAATCCTTTGTATATGCACAGTTGCAAATGTCAGATCCCATCCCAGAAC





TCAGAGGACAATTCCATGCATTCGTATGTTCTGAGATTCTTGATGCACTAAGGGGAACTAATAGTTTCA





CCCAGGATGAATCAAGAACTGTGACAACCAATTTGATATCCCCATTCCAAGATCTGACCCCAGATCTT





ACGGCTGAATTGCTCTGTATAATGAGGCTTTGGGGACACCCCATGCTCACCGCCAGTCAAGCTGCGGG





AAAGGTACGCGAGTCCATGTGTGCTGGAAAAGTATTAGACTTTCCCACCATTATGAAAACACTAGCCT





TTTTCCATACTATTCTGATCAATGGATACAGGAGGAAGCATCATGGAGTATGGCCACCCTTAAACTTAC





CGGGTAATGCTTCAAAGGGTCTCACGGAACTTATGAATGACAATACTGAGATAAGCTATGAATTCACA





CTTAAGCATTGGAAGGAAATCTCTCTTATAAAATTCAAGAAATGTTTTGATGCAGACGCAGGTGAGGA





ACTCAGTATATTTATGAAAGATAAAGCAATTAGTGCCCCAAAACAAGATTGGATGAGTGTGTTTAGAA





GAAGCCTAATCAAACAGCGCCATCAGCATCATCAGGTCCCCCTACCAAATCCATTCAATCGACGGCTA





TTGCTAAACTTTCTCGGAGATGACAAATTCGACCCGAATGTGGAGCTACAGTATGTAACATCAGGTGA





GTATCTACATGATGACACGTTTTGTGCATCATATTCACTAAAAGAGAAGGAAATTAAACCTGATGGTC





GAATTTTTGCAAAGTTGACTAAGAGAATGAGATCATGTCAAGTTATAGCAGAATCTCTTTTAGCGAAC





CATGCTGGGAAGTTAATGAAAGAGAATGGTGTTGTGATGAATCAGCTATCATTAACAAAATCACTATT





AACAATGAGTCAGATTGGAATAATATCCGAGAAAGCTAGAAAATCGACTCGAGATAACATAAATCAA





CCTGGTTTCCAGAATATCCAGAGAAATAAATCACATCACTCCAAGCAAGTCAATCAGCGAGATCCAAG





TGATGACTTTGAATTGGCAGCATCTTTTTTAACTACTGATCTCAAAAAATATTGTTTACAATGGAGGTA





CCAGACAATTATCCCATTTGCTCAATCATTAAACAGAATGTATGGTTATCCTCATCTCTTTGAGTGGAT





TCACTTACGGCTAATGCGTAGTACACTTTACGTGGGGGATCCCTTCAACCCACCAGCAGATACCAGTC





AATTTGATCTAGATAAAGTAATTAATGGAGATATCTTCATTGTATCACCCAGAGGTGGAATTGAAGGG





CTATGTCAAAAGGCTTGGACAATGATATCTATCTCTGTGATAATTCTATCTGCCACAGAGTCTGGCACA





CGAGTAATGAGTATGGTGCAGGGAGATAATCAAGCAATTGCTGTCACCACACGAGTACCAAGGAGCC





TGCCGACTCTTGAGAAAAAGACTATTGCTTTTAGATCTTGTAATCTATTCTTTGAGAGGTTAAAATGTA





ATAATTTTGGATTAGGTCACCATTTGAAAGAACAAGAGACTATCATTAGTTCTCACTTCTTTGTTTATA





GCAAGAGAATATTCTATCAGGGGAGGATTCTAACGCAAGCCTTAAAAAATGCTAGTAAGCTCTGCTTG





ACAGCTGATGTCCTAGGAGAATGTACCCAATCATCATGTTCTAATCTTGCAACTACTGTCATGAGGTTA





ACTGAGAATGGTGTTGAAAAAGATATCTGTTTCTACTTGAATATCTATATGACCATCAAACAGCTCTCC





TATGATATCATCTTCCCTCAAGTGTCAATTCCTGGAGATCAGATCACATTAGAATACATAAATAATCCA





CACCTGGTATCACGATTGGCTCTTCTGCCATCCCAGCTAGGAGGTCTAAACTACCTGTCATGCAGTAGG





CTGTTCAATCGAAACATAGGCGACCCGGTGGTTTCCGCAGTTGCAGATCTTAAGAGATTAATTAAATC





AGGATGTATGGATTACTGGATCCTTTATAACTTATTAGGGAGAAAACCGGGAAACGGCTCATGGGCTA





CTTTAGCAGCTGACCCGTACTCAATCAATATAGAGTATCAATACCCCCCAACTACAGCTCTTAAGAGG





CACACCCAACAAGCTCTGATGGAACTCAGTACGAATCCAATGTTACGTGGCATATTCTCTGACAATGC





ACAGGCAGAAGAAAATAATCTTGCTAGATTTCTCCTGGATAGGGAGGTGATCTTTCCGCGTGTAGCTC





ACATCATCATTGAGCAAACCAGTGTCGGGAGGAGAAAACAGATTCAAGGATATTTGGATTCAACTAG





ATCGATAATGAGTAAATCACTAGAAATTAAGCCCTTGTCCAATAGGAAGCTTAATGAAATACTGGATT





ACAACATCAATTACCTAGCTTACAATTTGGCATTACTCAAGAATGCTATTGAACCTCCGACTTATTTGA





AAGCAATGACTCTTGAAACATGTAGCATCGACATTGCAAGGAGCCTCCGGAAGCTCTCCTGGGCCCCA





CTCTTGGGTGGGAGAAATCTTGAAGGATTAGAGACGCCAGATCCCATTGAAATTACTGCAGGAGCATT





AATTGTTGGATCGGGCTACTGTGAACAGTGTGCTGCAGGAGACAATCGATTCACATGGTTTTTCTTGCC





ATCTGGTATCGAGATAGGAGGGGATCCCCGTGATAATCCTCCTATCCGTGTACCGTACATTGGCTCCA





GGACTGATGAGAGGAGGGTAGCCTCAATGGCATACATCAGGGGTGCCTCGAGTAGCCTAAAAGCAGT





TCTTAGACTGGCGGGAGTGTACATCTGGGCATTCGGAGATACTCTGGAGAATTGGATAGATGCACTGG





ATTTGTCTCACACTAGAGTTAACATCACACTTGAACAGCTGCAATCCCTCACCCCACTTCCAACCTCTG





CCAATCTAACCCATCGGTTGGATGATGGCACAACTACCCTAAAGTTTACTCCTGCGAGCTCTTACACCT





TTTCAAGTTTCACTCATATATCAAATGATGAGCAATACCTGACAATTAATGACAAAACTGCAGATTCA





AATATAATCTACCAACAGTTAATGATCACTGGACTCGGAATTTTAGAAACATGGAATAATCCCCCAAT





CAATAGAACATTCGAAGAATCTACCCTACATTTGCACACTGGTGCATCATGTTGTGTCCGACCTGTGGA





CTCCTGCATCATCTCAGAAGCATTAACAGTCAAGCCACATATTACAGTACCGTACAGCAATAAATTTG





TATTTGATGAAGACCCGCTATCTGAATATGAGACTGCAAAACTGGAATCGTTATCATTTCAAGCCCAA





TTAGGCAACATTGATGCTGTAGATATGACAGGTAAATTAACATTATTGTCCCAATTCACTGCAAGGCA





GATTATTAATGCAATCACTGGACTCGATGAGTCTGTCTCTCTTACTAATGATGCCATTGTTGCATCAGA





CTATGTCTCCAATTGGATTAGTGAATGCATGTATACCAAATTAGATGAATTATTTATGTATTGTGGGTG





GGAACTACTATTGGAACTATCCTATCAAATGTATTATCTGAGGGTAGTTGGGTGGAGTAATATAGTGG





ATTATTCTTACATGATCTTGAGAAGAATCCCGGGTGCAGCATTAAACAATCTGGCATCTACATTAAGTC





ATCCAAAACTTTTCCGACGAGCTATCAACCTAGATATAGTTGCCCCCTTAAATGCTCCTCATTTTGCAT





CTCTGGACTACATCAAGATGAGTGTGGATGCAATACTCTGGGGCTGTAAAAGAGTCATCAATGTGCTC





TCCAATGGAGGGGACTTAGAATTAGTTGTGACATCTGAAGATAGCCTTATTCTCAGTGACCGATCCAT





GAATCTCATTGCAAGGAAATTAACTTTATTATCACTGATTCACCATAATGGTTTGGAACTACCAAAGAT





TAAGGGGTTCTCTCCTGATGAGAAGTGTTTCGCTTTGACAGAATTTTTGAGGAAAGTGGTGAACTCAG





GGTTGAGTTCAATAGAGAACCTATCAAATTTTATGTACAATGTGGAGAACCCACGGCTTGCAGCATTC





GCCAGCAACAATTACTACCTGACCAGAAAATTATTGAATTCAATACGAGATACTGAGTCGGGTCAAGT





AGCAGTCACCTCATATTATGAATCATTAGAATATATTGATAGTCTTAAGCTAACCCCACATGTGCCTGG





TACCTCATGCATTGAGGATGATAGTCTATGTACAAATGATTACATAATCTGGATCATAGAGTCTAATGC





AAACTTGGAGAAGTATCCAATTCCAAATAGCCCTGAGGATGATTCCAATTTCCATAACTTTAAGTTGA





ATGCTCCATCGCACCATACCTTACGCCCATTAGGGTTGTCATCAACTGCTTGGTATAAGGGTATAAGCT





GTTGCAGGTACCTTGAGCGATTAAAGCTACCACAAGGTGATCATTTATATATTGCAGAAGGTAGTGGT





GCCAGTATGACAATCATAGAATACCTATTCCCAGGAAGAAAGATATATTACAATTCTTTATTTAGTAGT





GGTGACAATCCCCCACAAAGAAATTATGCACCAATGCCTACTCAGTTCATTGAGAGTGTCCCATACAA





GCTCTGGCAAGCACACACAGATCAATATCCCGAGATTTTTGAGGACTTCATCCCTCTATGGAACGGAA





ATGCCGCCATGACTGACATAGGAATGACAGCTTGTGTAGAATTCATCATCAATCGAGTCGGCCCAAGG





ACTTGCAGTTTAGTACATGTAGATTTGGAATCAAGTGCAAGCTTAAATCAACAATGCCTGTCAAAGCC





GATAATTAATGCTATCATCACTGCTACAACTGTTTTGTGCCCTCATGGGGTGCTTATTCTGAAATATAG





TTGGTTGCCATTTACTAGATTTAGTACTTTGATCACTTTCTTATGGTGCTACTTTGAGAGAATCACTGTT





CTTAGGAGCACATATTCTGGTCCAGCTAATCATGAGGTTTATTTAATTTGTATCCTTGCCAACAACTTT





GCATTCCAGACTGTCTCGCAGGCAACAGGAATGGCGATGACTTTAACCGATCAAGGGTTTACTTTGAT





ATCACCTGAAAGAATAAATCAGTATTGGGATGGTCACTTGAAGCAAGAACGTATCGTAGCAGAAGCA





ATTGATAAGGTGGTTCTAGGAGAAGATGCTCTATTCAATTCGAGTGATAATGAATTAATTCTCAAATGT





GGAGGGACACCAAATGCACGGAATCTTATCGATATCGAGCCAGTCGCAACTTTCATAGAATTTGAACA





ACTGATCTGCACAATGTTGACAACCCACTTGAAGGAAATAATTGATATAACAAGGTCTGGAACCCAGG





ATTATGAAAGTTTATTACTCACTCCTTACAATTTAGGTCTTCTTGGTAAAATCAGTACGATAGTGAGAT





TATTAACAGAAAGGATTCTAAATCATACTATCAGGAATTGGTTGATCCTCCCACCTTCGCTCCGGATGA





TCGTGAAGCAGGACTTGGAATTCGGCATATTCAGGATTACTTCCATCCTCAATTCTGATCGGTTCCTGA





AGCTTTCTCCAAATAGGAAATACTTGATTACACAATTAACTGCAGGCTACATTAGGAAATTGATTGAG





GGGGATTGTAATATCGATCTAACCAGACCTATCCAAAAACAAATCTGGAAAGCATTAGGTTGTGTAGT





CTATTGTCACGATCCAGTAGATCAAAGGGAATCAACAGAGTTTATTGATATAAATATTAATGAAGAAA





TAGACCGCGGGATCGATGGCGAGGAAATCTAAATATATCAAGAATCAGAATTAGTTTAAGAAAAAAG





AAGAGGATTAATCTTGGTTTTCCCCTTGGT.






20. CVL111


The nucleic acid sequence for CVL111 is:










(SEQ ID NO: 79)



ACCAGGGGGAAAACGAAGTGGTGACTCAAATCATCGAAGACCCTCGAGATTACATAGGTCCGGAACC






TATGGCCTTCGTGACCGACCTCGAGTCAGAGTAGTTCAATAAGGACCTATCAAGTTTGGGCAATTTTTC





GTCCCCGACACAAAAATGTCATCCGTGCTTAAAGCATATGAGCGATTCACACTCACTCAAGAACTGCA





AGATCAGAGTGAGGAAGGTACAATCCCACCTACAACACTAAAACCGGTAATCAGGGTATTTATACTAA





CCTCTAATAACCCAGAGCTAAGATCCCGGCTTCTTCTATTCTGCCTACGGATTGTTCTCAGTAATGGTG





CAAGGGATTCCCATCGCTTTGGAGCATTACTTACAATGTTTTCGCTACCATCAGCCACAATGCTCAATC





ATGTCAAATTAGCTGACCAGTCACCAGAAGCTGATATCGAAAGGGTAGAGATCGATGGCTTTGAGGA





GGGATCATTCCGCTTAATCCCCAATGCTCGTTCAGGTATGAGCCGTGGAGAGATCAATGCCTATGCTG





CACTTGCAGAAGATCTACCTGACACACTAAACCATGCAACACCTTTTGTTGATTCCGAAGTCGAGGGA





ACTGCATGGGATGAGATTGAGACTTTCTTAGATATGTGTTACAGTGTCCTAATGCAGGCATGGATAGT





GACTTGCAAGTGCATGACTGCGCCAGACCAACCTGCTGCTTCTATTGAGAAACGCCTGCAAAAATATC





GTCAGCAAGGCAGGATCAACCCGAGATATCTCCTGCAACCGGAGGCTCGAAGAATAATCCAGAATGT





AATCCGAAAGGGAATGGTGGTCAGACATTTCCTCACCTTTGAACTGCAGCTTGCCCGAGCACAAAGCC





TTGTATCAAATAGGTATTATGCTATGGTAGGGGATGTTGGAAAGTATATAGAGAATTGTGGAATGGGA





GGCTTCTTTTTGACACTAAAATATGCATTAGGAACCAGATGGCCCACACTTGCTTTAGCTGCATTTTCA





GGAGAGCTAACAAAGCTAAAGTCCCTCATGGCATTATACCAGACCCTTGGTGAGCAGGCCCGATATTT





GGCCCTATTGGAGTCACCACATTTGATGGATTTTGCTGCAGCAAACTACCCACTGCTATATAGCTATGC





TATGGGAATAGGCTATGTGTTAGATGTCAACATGAGGAACTACGCTTTCTCCAGATCATACATGAATA





AGACATATTTCCAATTGGGAATGGAAACTGCAAGAAAACAACAGGGTGCAGTTGACATGAGGATGGC





AGAAGATCTCGGTCTAACTCAAGCCGAACGCACCGAGATGGCAAATACACTTGCCAAATTGACCACA





GCAAATCGAGGGGCAGACACCAGGGGAGGAGTCAACCCGTTCTCATCTATCACTGGGACAACTCAGG





TGCCCGCTGCAGCAACAGGTGACACATTCGAGAGTTACATGGCAGCGGATCGACTGAGGCAGAGATA





TGCTGATGCAGGCACCCACGATGATGAGATGCCACCATTGGAAGAGGAGGAAGAGGACGACACATCT





GCAGGTCCACGCACTGGACTAACTCTTGAACAAGTGGCCTTGGACATCCAGAACGCAGCAGTTGGAGC





TCCCATCCATACAGATGACCTGAATGCCGCACTGGGTGATCTTGACATCTAGACAATTCAGATCCCAA





TCTTAAATCGACACACCTAATTGACCAGTTAGATGGAACTACAGTGGATTCCATAAGGTTCCTGCCTAC





CATCGGCTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCCGATGCCAATAACA





CAATCCACAATCTACAATGGATCCCACTGATCTGAGCTTCTCCCCAGATGAGATCAATAAGCTCATAG





AGACAGGCCTGAATACTGTGGAGTATTTTACTTCCCAACAAGTCACAGGAACATCCTCTCTTGGAAAG





AATACAATACCACCAGGGGTCACAGGACTACTAACCAATGCTGCAGAGGCAAAGATCCAAGAGTCAA





CCAACCATCAGAAGGGTTCAGTTGGTGGGGGCGCAAAACCAAAGAAACCGCGACCAAAAATTGCCAT





TGTGCCAGCAGATGACAAAACGGTGCCCGGAAAGCCGATCCCAAACCCTCTATTAGGTCTGGACTCCA





CCCCGAGCACCCAAACTGTGCTTGATCTAAGTGGGAAAACATTACCATCAGGATCCTATAAGGGGGTT





AAACTTGCGAAATTTGGAAAAGAAAATCTGATGACACGGTTCATCGAGGAACCCAGAGAGAATCCTA





TCGCAACCAATTCCCCCATCGATTTTAAGAGGGGCAGGGATACCGGCGGGTTCCATAGAAGGGAGTAC





TCAATCGGATGGGTGGGAGATGAAGTCAAGGTCACTGAGTGGTGCAATCCATCCTGTTCTCCAATCAC





CGCTGCAGCAAGGCGATTTGAATGCACTTGTCACCAGTGTCCAGTCACTTGCTCTGAATGTGAACGAG





ATACTTAATACAGTGAGAAATTTGGACTCTCGGATGAATCAACTGGAGACAAAAGTAGATCGCATTCT





CTCATCTCAGTCTCTAATCCAGACCATCAAGAATGACATAGTTGGACTTAAAGCAGGGATGGCTACTT





TAGAAGGAATGATTACAACTGTGAAAATCATGGACCCGGGAGTTCCCAGTAATGTTACTGTGGAAGAT





GTACGCAAGAAACTAAGTAACCATGCTGTTGTTGTGCCAGAATCATTCAATGATAGTTTCTTGACTCAA





TCTGAAGATGTAATTTCACTTGATGAGTTGGCTCGACCAACTGCAACAAGTGTTAAGAAGATTGTCAG





GAAGGTTCCTCCTCAGAAGGATCTGACTGGATTGAAGATCACACTAGAGCAATTGGCAAAGGATTGCA





TCAGCAAACCGAAGATGAGGGAAGAGTATCTCCTCAAAATCAACCAGGCTTCCAGTGAGGCTCAGCT





AATTGACCTCAAGAAAGCAATCATCCGCAGTGCAATTTGATCAAGAAACACCCAATTACACTACACTG





GTATGACACTGTACTAACCCTGAGGGTTTTAGAAAAAACGATTAACGATAAATAAGCCCGAACACTAC





ACACCACCCGAGGCAGCCATGCCATCCATCAGCATCCCCGCAGACCCCACCAATCCACGTCAATCAAT





AAAAGCGTTCCCAATTGTGATCAACCGTGATGGGGGTGAGAAAGGTCGCTTGGTTAAACAACTACGCA





CAACCTACTTGAATGACCTAGATACTCATGAGCCACTGGTGACATTCGTAAATACTTATGGATTCATCT





ACGAACAGGATCGGGGAAATACCATTGTCGGAGAGGATCAACATGGGAAGAAAAGAGAGGCTGTGA





CTGCTGCAATGGTTACCCTTGGATGTGGGCCTAATCTACCATCATTAGGGAATGTCCTGGGACAACTG





AGTGAATTCCAGGTCATTGTTAGGAAGACATCCAGCAAAGCGGAAGAGATGGTCTTTGAAATTGTTAA





GTATCCGAGAATATTTCGGGGTCATACATTAATCCAGAAAGGACTAGTCTGTGTCTCCGCAGAAAAAT





TTGTTAAGTCACCAGGGAAAGTACAATCTGGAATGGACTATCTCTTCATTCCGACATTTCTGTCAGTGA





CTTACTGTCCAGCTGCAATCAAATTTCAGGTACCTGGCCCCATGTTGAAAATGAGATCAAGATACACT





CAGAGCTTACAACTTGAACTAATGATAAGAATCCTGTGTAAGCCCGATTCGCCACTTATGAAGGTCCA





TATCCCTGACAAGGAAGGAAGAGGATGTCTTGTATCAGTATGGTTGCATGTATGCAATATCTTCAAAT





CAGGAAACAAGAATGGCAGTGAGTGGCAGGAATACTGGATGAGAAAGTGTGCTAACATGCAACTTGA





AGTGTCGATTGCAGATATGTGGGGACCAACTATCATAATTCATGCCAGAGGTCACATTCCCAAAAGTG





CTAAGTTGTTTTTTGGAAAGGGTGGATGGAGCTGCCATCCACTTCACGAAGTTGTTCCAAGTGTCACTA





AAACACTATGGTCCGTGGGCTGTGAGATTACAAAGGCGAAGGCAATAATACAAGAGAGTAGCATCTC





TCTTCTCGTGGAGACTACTGACATCATAAGTCCAAAAGTCAAAATTTCATCTAAGCATCGCCGCTTTGG





GAAATCAAATTGGGGTCTGTTCAAGAAAACCAAATCACTGCCCAACCTGACGGAGCTGGAATGACTG





ACCCCCAATCGAGACTACACCACCTCAAACTATAGGTGGGTGGTACCTCAGTGATTAATCTCGTAAGC





ACTGATCGTAGGCTACAACACACTAATATTATCCAGATTAGAGAGCTTAATTAGCTCTGTATTAATAAT





AACACTACTATTCCAATAACTGGAATCACCAGCTTGATTTATCTCCAAAATGATTCAAAGAAAACAAA





TCATATTAAGACTATCCTAAGCACGAACCCATATCGTCCTTCAAATCATGGGTACTATAATTCAATTTC





TGGTGGTCTCCTGTCTATTGGCAGGAGCAGGCAGTCTTGATCCAGCAGCCCTCATGCAAATCGGTGTC





ATTCCAACAAATGTCCGGCAACTTATGTATTATACTGAGGCCTCATCAGCATTCATTGTTGTGAAGTTA





ATGCCTACAATTGACTCGCCGATTAGTGGATGTAATATAACATCAATTTCAAGCTATAATGCAACAGT





GACAAAACTCCTACAGCCGATCGGTGAGAATTTGGAGACGATTAGGAACCAGTTGATTCCAACTCGGA





GGAGACGCCGGTTTGCAGGGGTGGTGATTGGATTAGCTGCATTAGGAGTAGCTACTGCCGCACAGGTC





ACTGCCGCAGTAGCACTAGTAAAGGCAAATGAAAATGCTGCGGCTATACTCAATCTCAAAAATGCAAT





CCAAAAAACAAATGCAGCAGTTGCAGATGTGGTCCAGGCCACACAATCACTAGGAACaGCAGTTCAAG





CAGTTCAAGATCACATAAACAGTGTGGTAAGTCCAGCAATTACAGCAGCCAATTGTAAAGCCCAAGAT





GCTATCATTGGCTCAATCCTCAATCTCTATTTGACCGAGTTGACAACTATCTTCCACAATCAAATTACA





AACCCTGCATTGAGTCCTATTACAATTCAAGCTTTAAGGATCCTACTAGGGAGTACCTTGCCGACTGTG





GTCGAAAAATCTTTCAATACCCAGATAAGTGCGGCTGAGCTTCTCTCATCAGGGTTATTGACAGGCCA





GATTGTGGGATTAGATTTGACCTATATGCAGATGGTCATAAAAATTGAGCTGCCAACTTTAACTGTAC





AACCTGCAACCCAGATCATAGATCTGGCCACCATTTCTGCATTCATTAACAATCAAGAAGTCATGGCC





CAATTACCAACACGTGTTATTGTGACTGGCAGCTTGATCCAAGCCTATCCCGCATCGCAATGCACTATT





ACACCCAACACTGTGTACTGTAGGTATAATGATGCCCAAGTACTCTCAGATGATACGATGGCTTGCCT





CCAAGGTAACTTGACAAGATGCACCTTCTCTCCAGTGGTTGGGAGCTTTCTCACTCGATTCGTGCTGTT





CGATGGAATAGTTTATGCAAATTGCAGGTCGATGTTGTGCAAGTGCATGCAGCCTGCTGCTGTGATCCT





ACAGCCGAGTTCATCCCCTGTAACTGTCATTGACATGTACAAATGTGTGAGTCTGCAGCTTGACAATCT





CAGATTCACCATCACTCAATTGGCCAATGTAACCTACAATAGCACCATCAAGCTTGAAACATCCCAGA





TCTTGCCTATTGATCCGTTGGATATATCCCAGAATCTAGCTGCGGTGAATAAGAGTCTAAGTGATGCAC





TACAACACTTAGCACAAAGTGACACATACCTTTCTGCAATCACATCAGCTACGACTACAAGTGTATTA





TCCATAATAGCAATCTGTCTTGGATCGTTAGGTTTAATATTAATAATCTTGCTCAGTGTAGTTGTGTGG





AAGTTATTGACCATTGTCGCTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAATTCAGCATTC





CACCACTCACGATCTGATCTCAGTGAGAAAAATCAACCTGCAACTCTTGGAACAAGATAAGACAGTCA





TCCATTAGTAATTTTTAAGAAAAAAACGATAGGACCGAAACTAGTATTGAAAGAACCGTCTCGGTCAA





TCTAGGTAATCGAGCTGcTACCGTCTCGGAAAGCTCAAATCATGCTGCCTGATCCGGAAGATCCGGAA





AGCAAAAAAGCTACAAGGAGAACAGGAAACCTAATTATCTGCTTCCTATTCATCTTCTTTCCGTTTGTA





AACTTCATTGTTCCAACTCTAAGACACTTGCTGTCCTAACACCTGCTATAGGCTATCCACTGCATCATC





TCTTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCCGGTGCCAACAACACAAT





CCACAATCTACAGTCGACGCGGCCGCCACCatgttcgtcttcctggtcctgctgcctctggtctcctc





acagtgcgtcaatctgATCactcggactcagTCCtatactaatagcttcaccagaggcgtgtactatcc





tgacaaggtgtttagaagctccgtgctgcactctacacaggatctgtttctgccattctttagcaacgt





gacctggttccacgccatccacgtgagcggcaccaatggcacaaagcggttcgacaatcccgtgctg





ccttttaacgatggcgtgtacttcgcctctaccgagaagagcaacatcatcagaggctggatctttggc





accacactggactccaagacacagtctctgctgatcgtgaacaatgccaccaacgtggtcatcaaggtgt





gcgagttccagttttgtaatgatcccttcctgGACgtgtactatcacGAGaacaataagagcAGAatgga





gtccgagCTGagagtgtattctagcgccaacaactgcacatttgagtacgtgagccagcctttcctga





tggacctggagggcaagcagggcaatttcaagaacctgagggagttcgtgtttaagaatatcgacggc





tacttcaaaatctactctaagcacacccccGTGaacctgGGCcgcgacctgcctcagggcttcag





cgccctggagcccctggtggatctgcctatcggcatcaacatcacccggtttcagacactgctggcc





ctgcacagaagctacctgacacccggcgactcctctagcAGCtggaccgccggcgctgccgcctacta





tgtgggctacctccagccccggaccttcctgctgaagtacaacgagaatggcaccatcacagacgcag





tggattgcgccctggaccccctgagcgagacaaagtgtacactgaagtcctttaccgtggagaagggc





atctatcagacatccaatttcagggtgcagccaaccgagtctatcgtgcgctttcctaatatcacaaacc





tgtgcccatttCACgaggtgttcaacgcaacccgcttcgccagcgtgtacgcctggaataggaagcgga





tcagcaactgcgtggccgactatagcgtgctgtacaacCTGgccCCCttcTTCGCCtttaagtgctatg





gcgtgtcccccacaaagctgaatgacctgtgctttaccaacgtctacgccgattctttcgtgatcagg





ggcAACgaggtgTCCcagatcgcccccggccagacaggcAATatcgcagactacaattataagctgccag





acgatttcaccggctgcgtgatcgcctggaacagcaacAAGctggattccaaagtgTCCggcaactac





aattatctgtaccggctgtttagaaagagcAAGctgaagcccttcgagagggacatctctacagaaat





ctaccaggccggcAATAAGccttgcaatggcgtgGCCggctttaactgttatttcccactcCAGtccta





cggcttcCGCcccacaTATggcgtgggcCACcagccttaccgcgtggtggtgctgagctttgagctgctg





cacgccccagcaacagtgtgcggccccaagaagtccaccaatctggtgaagaacaagtgcgtgaacttca





acttcaacggcctgaccggcacaggcgtgctgaccgagtccaacaagaagttcctgccatttcagca





gttcggcagggacatcgcagataccacagacgccgtgcgcgacccacagaccctggagatcctggaca





tcacaccctgctctttcggcggcgtgagcgtgatcacacccggcaccaatacaagcaaccaggtggcc





gtgctgtatcagGGCgtgaattgtaccgaggtgcccgtggctatccacgccgatcagctgaccccaa





catggcgggtgtacagcaccggctccaacgtcttccagacaagagccggatgcctgatcggagcagagTA





Cgtgaacaattcctatgagtgcgacatcccaatcggcgccggcatctgtgcctcttaccagacccagac





aAAGtctCACagaagagcccggagcgtggcctcccagtctatcatcgcctataccatgtccctgggcgcc





gagaacagcgtggcctactctaacaatagcatcgccatcccaaccaacttcacaatctctgtgaccacag





agatcctgcccgtgtccatgaccaagacatctgtggactgcacaatgtatatctgtggcgattcta





ccgagtgcagcaacctgctgctccagtacggcagcttttgtacccagctgAAGagagccctgacaggc





atcgccgtggagcaggataagaacacacaggaggtgttcgcccaggtgaagcaaatctacaagaccccc





cctatcaagTACtttggcggcttcaatttttcccagatcctgcctgatccatccaagccttctaagcgga





gctttatcgaggacctgctgttcaacaaggtgaccctggccgatgccggcttcatcaagcagtatggcga





ttgcctgggcgacatcgcagccagggacctgatctgcgcccagaagtttaatggcctgaccgtgctgcc





acccctgctgacagatgagatgatcgcacagtacacaagcgccctgctggccggcaccatcacatc





cggatggaccttcggcgcaggagccgccctccagatcccctttgccatgcagatggcctataggttca





acggcatcggcgtgacccagaatgtgctgtacgagaaccagaagctgatcgccaatcagtttaactcc





gccatcggcaagatccaggacagcctgtcctctacagccagcgccctgggcaagctccaggatgtgg





tgaatCACaacgcccaggccctgaataccctggtgaagcagctgagcagcAAGttcggcgccatctcta





gcgtgctgaatgacatcctgagccggctggacaaggtggaggcagaggtgcagatcgaccggctgatca





ccggccggctccagagcctccagacctatgtgacacagcagctgatcagggccgccgagatcagggccag





cgccaatctggcagcaaccaagatgtccgagtgcgtgctgggccagtctaagagagtggacttttgtg





gcaagggctatcacctgatgtccttccctcagtctgccccacacggcgtggtgtttctgcacgtgacct





acgtgcccgcccaggagaagaacttcaccacagcccctgccatctgccacgatggcaaggcccactttc





caagggagggcgtgttcgtgtccaacggcacccactggtttgtgacacagcgcaatttctacgagcccca





gatcatcaccacagacaacaccttcgtgagcggcaactgtgacgtggtcatcggcatcgtgaacaat





accgtgtatgatccactccagcccgagctggacagctttaaggaggagctggataagtatttcaagaatc





acacctcccctgacgtggatctgggcgacatcagcggcatcaatgcctccgtggtgaacatccagaagg





agatcgaccgcctgaacgaggtggctaagaatctgaacgagagcctgatcgacctccaggagctgggca





agtatgagcagtacatcaagtggccctggtacatctggctgggcttcatcgccggcctgatcgccatc





gtgatggtgaccatcatgctgtgctgtatgacatcctgctgttcttgcctgaagggctgctgtagct





gtggctcctgctgtAAGTTATTGACCATTGTCGTTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCA





TAAATGAGCTAGCCTCCTGCCATACTTCCTACTCACATCATATCTATTTTAAAGAAAAAATAGGCCCGA





ACACTAATCGTGCCGGCAGTGCCACTGCACACACAACACTACACATACAATACACTACAATGGTTGCA





GAAGATGCCCCTGTTAGGGGCACTTGCCGAGTATTATTTCGAACAACAACTTTAATTTTTCTATGCACA





CTATTAGCATTAAGCATCTCTATCCTTTATGAGAGTTTAATAACCCAAAAGCAAATCATGAGCCAAGC





AGGCTCAACTGGATCTAATTCTAGATTAGGAAGTATCACTGATCTTCTTAATAATATTCTCTCTGTCGC





AAATCAGATTATATATAACTCTGCAGTCGCTCTACCTCTACAATTGGACACTCTTGAATCAACACTCCT





TACAGCCATTAAGTCTCTTCAAACAAGTGACAAGCTAGAACAGAACTGCTCGTGGGGTGCTGCACTGA





TTAATGATAATAGATACATTAATGGCATCAATCAGTTCTATTTCTCAATTGCTGAGGGTCGCAAGCTGA





CACTTGGCCCACTTCTTAATATACCTAGTTTCATTCCAACTGCCACGACACCAGAGGGCTGCACCAGGA





TCCCATCATTCTCGCTCACCAAGACACACTGGTGTTATACACACAATGTTATCCTGAATGGATGCCAGG





ATCATGTATCCTCAAATCAATTTGTTTCCATGGGAATCATTGAACCCACTTCTGCCGGGTTTCCATCCTT





TCGAACCCTAAAGACTCTATATCTCAGCGATGGGGTCAATCGTAAGAGCTGCTCTATCAGTACAGTTC





CGGGGGGTTGTATGATGTACTGTTTCGTCTCTACTCAACCAGAGAGGGATGACTACTTTTCTACCGCTC





CTCCAGAACAACGAATTATTATAATGTACTATAATGATACAATCGTGGAGCGCATAATTAATCCACCC





GGGGTACTAGATGTATGGGCAACATTGAACCCAGGAACAGGAAGCGGGGTATATTATTTAGGTTGGGT





ACTCTTTCCAATATATGGCGGCGTGATTAAAGATACGAGTTTATGGAATAATCAAGCAAATAAATACT





TTATCCCCCAGATGGTTGCTGCTCTCTGCTCACAAAACCAGGCAACTCAAGTCCAAAATGCTAAGTCAT





CATACTATAGCAGCTGGTTTGGCAATCGAATGATTCAGTCTGGGATCCTGGCATGTCCTCTTCAACAGG





ATCTAACCAATGAGTGTTTAGTTCTGCCCTTTTCTAATGATCAGGTGCTTATGGGTGCTGAAGGGAGAT





TATACATGTATGGTGACTCGGTGTATTACTACCAAAGAAGCAATAGTTGGTGGCCTATGACCATGCTG





TATAAGGTAACCATAACATTCACTAATGGTCAGCCATCTGCTATATCAGCTCAGAATGTGCCCACACA





GCAGGTCCCTAGACCTGGGACAGGAAGCTGCTCTGCAACAAATAGATGTCCCGGTTTTTGCTTGAAAG





GAGTGTATGCTGATGCCTGGTTACTGACCAACCCTTCGTCTACCAGTACATTTGGATCAGAAGCAACCT





TCACTGGTTCTTATCTCAACGCAGCAACTCAGCGTATCAATCCGACGATGTATATCGCGAACAACACA





CAGATCATAAGCTCACAGCAATTTGGATCAAGCGGTCAAGAAGCAGCATATGGCCACACAACTTGTTT





TAGGGACACAGGCTCTGTTATGGTATACTGTATCTATATTATTGAATTGTCCTCATCTCTCTTAGGACA





ATTTCAGATTGTCCCATTTATCCGTCAGGTGACACTATCCTAAAGGCAGAAGCCTCCAGGTCTGACCCA





GCCAATCAAAGCATTATACCAGACCATGGAATGCATACCAAACATTATTGACACTAATGACACACAAA





ATTGGTTTTAAGAAAAACCAAGAGAACAATAGGCCAGAATGGCTGGGTCTCGGGAGATATTACTCCCT





GAAGTCCATCTCAATTCACCAATTGTAAAGCATAAGCTATACTATTACATTCTACTTGGAAACCTCCCA





AATGAGATCGACATTGACGATTTAGGTCCATTACATAATCAAAATTGGAATCAAATAGCACATGAAGA





GTCTAACTTAGCCCAACGCTTGGTAAATGTAAGAAATTTTCTAATTACCCACATCCCTGATCTTAGAAA





GGGCCATTGGCAAGAGTATGTCAATGTAATACTGTGGCCGCGAATTCTTCCCTTGATCCCGGATTTTAA





AATCAATGACCAATTGCCTCTACTCAAAAATTGGGACAAGTTAGTTAAAGAATCATGTTCAGTAATCA





ATGCGGGTACTTCCCAGTGCATTCAGAATCTCAGCTATGGACTGACAGGTCGTGGGAACCTCTTTACA





CGATCACGTGAACTCTCTGGTGACCGCAGGGATATTGATCTTAAGACGGTTGTGGCAGCATGGCATGA





CTCAGACTGGAAAAGAATAAGTGATTTTTGGATTATGATCAAATTCCAGATGAGACAATTAATTGTTA





GGCAAACAGATCATAATGATCCTGATTTAATCACGTATATCGAAAATAGAGAAGGCATAATCATCATA





ACCCCTGAACTGGTAGCATTATTTAACACTGAGAATCATACACTAACATACATGACCTTTGAAATTGTA





CTGATGGTTTCAGATATGTACGAAGGTCGTCACAACATTTTATCACTATGCACAGTTAGCACTTACCTG





AATCCTCTGAAGAAAAGAATAACATATTTATTGAGCCTTGTAGATAACTTAGCTTTTCAGATAGGTGAT





GCTGTATATAACATAATTGCTTTGCTAGAATCCTTTGTATATGCACAGTTGCAAATGTCAGATCCCATC





CCAGAACTCAGAGGACAATTCCATGCATTCGTATGTTCTGAGATTCTTGATGCACTAAGGGGAACTAA





TAGTTTCACCCAGGATGAATCAAGAACTGTGACAACCAATTTGATATCCCCATTCCAAGATCTGACCC





CAGATCTTACGGCTGAATTGCTCTGTATAATGAGGCTTTGGGGACACCCCATGCTCACCGCCAGTCAA





GCTGCGGGAAAGGTACGCGAGTCCATGTGTGCTGGAAAAGTATTAGACTTTCCCACCATTATGAAAAC





ACTAGCCTTTTTCCATACTATTCTGATCAATGGATACAGGAGGAAGCATCATGGAGTATGGCCACCCTT





AAACTTACCGGGTAATGCTTCAAAGGGTCTCACGGAACTTATGAATGACAATACTGAGATAAGCTATG





AATTCACACTTAAGCATTGGAAGGAAATCTCTCTTATAAAATTCAAGAAATGTTTTGATGCAGACGCA





GGTGAGGAACTCAGTATATTTATGAAAGATAAAGCAATTAGTGCCCCAAAACAAGATTGGATGAGTGT





GTTTAGAAGAAGCCTAATCAAACAGCGCCATCAGCATCATCAGGTCCCCCTACCAAATCCATTCAATC





GACGGCTATTGCTAAACTTTCTCGGAGATGACAAATTCGACCCGAATGTGGAGCTACAGTATGTAACA





TCAGGTGAGTATCTACATGATGACACGTTTTGTGCATCATATTCACTAAAAGAGAAGGAAATTAAACC





TGATGGTCGAATTTTTGCAAAGTTGACTAAGAGAATGAGATCATGTCAAGTTATAGCAGAATCTCTTTT





AGCGAACCATGCTGGGAAGTTAATGAAAGAGAATGGTGTTGTGATGAATCAGCTATCATTAACAAAAT





CACTATTAACAATGAGTCAGATTGGAATAATATCCGAGAAAGCTAGAAAATCGACTCGAGATAACAT





AAATCAACCTGGTTTCCAGAATATCCAGAGAAATAAATCACATCACTCCAAGCAAGTCAATCAGCGAG





ATCCAAGTGATGACTTTGAATTGGCAGCATCTTTTTTAACTACTGATCTCAAAAAATATTGTTTACAAT





GGAGGTACCAGACAATTATCCCATTTGCTCAATCATTAAACAGAATGTATGGTTATCCTCATCTCTTTG





AGTGGATTCACTTACGGCTAATGCGTAGTACACTTTACGTGGGGGATCCCTTCAACCCACCAGCAGAT





ACCAGTCAATTTGATCTAGATAAAGTAATTAATGGAGATATCTTCATTGTATCACCCAGAGGTGGAAT





TGAAGGGCTATGTCAAAAGGCTTGGACAATGATATCTATCTCTGTGATAATTCTATCTGCCACAGAGTC





TGGCACACGAGTAATGAGTATGGTGCAGGGAGATAATCAAGCAATTGCTGTCACCACACGAGTACCA





AGGAGCCTGCCGACTCTTGAGAAAAAGACTATTGCTTTTAGATCTTGTAATCTATTCTTTGAGAGGTTA





AAATGTAATAATTTTGGATTAGGTCACCATTTGAAAGAACAAGAGACTATCATTAGTTCTCACTTCTTT





GTTTATAGCAAGAGAATATTCTATCAGGGGAGGATTCTAACGCAAGCCTTAAAAAATGCTAGTAAGCT





CTGCTTGACAGCTGATGTCCTAGGAGAATGTACCCAATCATCATGTTCTAATCTTGCAACTACTGTCAT





GAGGTTAACTGAGAATGGTGTTGAAAAAGATATCTGTTTCTACTTGAATATCTATATGACCATCAAAC





AGCTCTCCTATGATATCATCTTCCCTCAAGTGTCAATTCCTGGAGATCAGATCACATTAGAATACATAA





ATAATCCACACCTGGTATCACGATTGGCTCTTCTGCCATCCCAGCTAGGAGGTCTAAACTACCTGTCAT





GCAGTAGGCTGTTCAATCGAAACATAGGCGACCCGGTGGTTTCCGCAGTTGCAGATCTTAAGAGATTA





ATTAAATCAGGATGTATGGATTACTGGATCCTTTATAACTTATTAGGGAGAAAACCGGGAAACGGCTC





ATGGGCTACTTTAGCAGCTGACCCGTACTCAATCAATATAGAGTATCAATACCCCCCAACTACAGCTCT





TAAGAGGCACACCCAACAAGCTCTGATGGAACTCAGTACGAATCCAATGTTACGTGGCATATTCTCTG





ACAATGCACAGGCAGAAGAAAATAATCTTGCTAGATTTCTCCTGGATAGGGAGGTGATCTTTCCGCGT





GTAGCTCACATCATCATTGAGCAAACCAGTGTCGGGAGGAGAAAACAGATTCAAGGATATTTGGATTC





AACTAGATCGATAATGAGTAAATCACTAGAAATTAAGCCCTTGTCCAATAGGAAGCTTAATGAAATAC





TGGATTACAACATCAATTACCTAGCTTACAATTTGGCATTACTCAAGAATGCTATTGAACCTCCGACTT





ATTTGAAAGCAATGACTCTTGAAACATGTAGCATCGACATTGCAAGGAGCCTCCGGAAGCTCTCCTGG





GCCCCACTCTTGGGTGGGAGAAATCTTGAAGGATTAGAGACGCCAGATCCCATTGAAATTACTGCAGG





AGCATTAATTGTTGGATCGGGCTACTGTGAACAGTGTGCTGCAGGAGACAATCGATTCACATGGTTTTT





CTTGCCATCTGGTATCGAGATAGGAGGGGATCCCCGTGATAATCCTCCTATCCGTGTACCGTACATTGG





CTCCAGGACTGATGAGAGGAGGGTAGCCTCAATGGCATACATCAGGGGTGCCTCGAGTAGCCTAAAA





GCAGTTCTTAGACTGGCGGGAGTGTACATCTGGGCATTCGGAGATACTCTGGAGAATTGGATAGATGC





ACTGGATTTGTCTCACACTAGAGTTAACATCACACTTGAACAGCTGCAATCCCTCACCCCACTTCCAAC





CTCTGCCAATCTAACCCATCGGTTGGATGATGGCACAACTACCCTAAAGTTTACTCCTGCGAGCTCTTA





CACCTTTTCAAGTTTCACTCATATATCAAATGATGAGCAATACCTGACAATTAATGACAAAACTGCAG





ATTCAAATATAATCTACCAACAGTTAATGATCACTGGACTCGGAATTTTAGAAACATGGAATAATCCC





CCAATCAATAGAACATTCGAAGAATCTACCCTACATTTGCACACTGGTGCATCATGTTGTGTCCGACCT





GTGGACTCCTGCATCATCTCAGAAGCATTAACAGTCAAGCCACATATTACAGTACCGTACAGCAATAA





ATTTGTATTTGATGAAGACCCGCTATCTGAATATGAGACTGCAAAACTGGAATCGTTATCATTTCAAGC





CCAATTAGGCAACATTGATGCTGTAGATATGACAGGTAAATTAACATTATTGTCCCAATTCACTGCAA





GGCAGATTATTAATGCAATCACTGGACTCGATGAGTCTGTCTCTCTTACTAATGATGCCATTGTTGCAT





CAGACTATGTCTCCAATTGGATTAGTGAATGCATGTATACCAAATTAGATGAATTATTTATGTATTGTG





GGTGGGAACTACTATTGGAACTATCCTATCAAATGTATTATCTGAGGGTAGTTGGGTGGAGTAATATA





GTGGATTATTCTTACATGATCTTGAGAAGAATCCCGGGTGCAGCATTAAACAATCTGGCATCTACATTA





AGTCATCCAAAACTTTTCCGACGAGCTATCAACCTAGATATAGTTGCCCCCTTAAATGCTCCTCATTTT





GCATCTCTGGACTACATCAAGATGAGTGTGGATGCAATACTCTGGGGCTGTAAAAGAGTCATCAATGT





GCTCTCCAATGGAGGGGACTTAGAATTAGTTGTGACATCTGAAGATAGCCTTATTCTCAGTGACCGAT





CCATGAATCTCATTGCAAGGAAATTAACTTTATTATCACTGATTCACCATAATGGTTTGGAACTACCAA





AGATTAAGGGGTTCTCTCCTGATGAGAAGTGTTTCGCTTTGACAGAATTTTTGAGGAAAGTGGTGAAC





TCAGGGTTGAGTTCAATAGAGAACCTATCAAATTTTATGTACAATGTGGAGAACCCACGGCTTGCAGC





ATTCGCCAGCAACAATTACTACCTGACCAGAAAATTATTGAATTCAATACGAGATACTGAGTCGGGTC





AAGTAGCAGTCACCTCATATTATGAATCATTAGAATATATTGATAGTCTTAAGCTAACCCCACATGTGC





CTGGTACCTCATGCATTGAGGATGATAGTCTATGTACAAATGATTACATAATCTGGATCATAGAGTCTA





ATGCAAACTTGGAGAAGTATCCAATTCCAAATAGCCCTGAGGATGATTCCAATTTCCATAACTTTAAG





TTGAATGCTCCATCGCACCATACCTTACGCCCATTAGGGTTGTCATCAACTGCTTGGTATAAGGGTATA





AGCTGTTGCAGGTACCTTGAGCGATTAAAGCTACCACAAGGTGATCATTTATATATTGCAGAAGGTAG





TGGTGCCAGTATGACAATCATAGAATACCTATTCCCAGGAAGAAAGATATATTACAATTCTTTATTTAG





TAGTGGTGACAATCCCCCACAAAGAAATTATGCACCAATGCCTACTCAGTTCATTGAGAGTGTCCCAT





ACAAGCTCTGGCAAGCACACACAGATCAATATCCCGAGATTTTTGAGGACTTCATCCCTCTATGGAAC





GGAAATGCCGCCATGACTGACATAGGAATGACAGCTTGTGTAGAATTCATCATCAATCGAGTCGGCCC





AAGGACTTGCAGTTTAGTACATGTAGATTTGGAATCAAGTGCAAGCTTAAATCAACAATGCCTGTCAA





AGCCGATAATTAATGCTATCATCACTGCTACAACTGTTTTGTGCCCTCATGGGGTGCTTATTCTGAAAT





ATAGTTGGTTGCCATTTACTAGATTTAGTACTTTGATCACTTTCTTATGGTGCTACTTTGAGAGAATCAC





TGTTCTTAGGAGCACATATTCTGGTCCAGCTAATCATGAGGTTTATTTAATTTGTATCCTTGCCAACAA





CTTTGCATTCCAGACTGTCTCGCAGGCAACAGGAATGGCGATGACTTTAACCGATCAAGGGTTTACTTT





GATATCACCTGAAAGAATAAATCAGTATTGGGATGGTCACTTGAAGCAAGAACGTATCGTAGCAGAA





GCAATTGATAAGGTGGTTCTAGGAGAAGATGCTCTATTCAATTCGAGTGATAATGAATTAATTCTCAA





ATGTGGAGGGACACCAAATGCACGGAATCTTATCGATATCGAGCCAGTCGCAACTTTCATAGAATTTG





AACAACTGATCTGCACAATGTTGACAACCCACTTGAAGGAAATAATTGATATAACAAGGTCTGGAACC





CAGGATTATGAAAGTTTATTACTCACTCCTTACAATTTAGGTCTTCTTGGTAAAATCAGTACGATAGTG





AGATTATTAACAGAAAGGATTCTAAATCATACTATCAGGAATTGGTTGATCCTCCCACCTTCGCTCCGG





ATGATCGTGAAGCAGGACTTGGAATTCGGCATATTCAGGATTACTTCCATCCTCAATTCTGATCGGTTC





CTGAAGCTTTCTCCAAATAGGAAATACTTGATTACACAATTAACTGCAGGCTACATTAGGAAATTGAT





TGAGGGGGATTGTAATATCGATCTAACCAGACCTATCCAAAAACAAATCTGGAAAGCATTAGGTTGTG





TAGTCTATTGTCACGATCCAGTAGATCAAAGGGAATCAACAGAGTTTATTGATATAAATATTAATGAA





GAAATAGACCGCGGGATCGATGGCGAGGAAATCTAAATATATCAAGAATCAGAATTAGTTTAAGAAA





AAAGAAGAGGATTAATCTTGGTTTTCCCCTTGGT.






21. CVL113


The nucleic acid sequence for CVL116 is:










(SEQ ID NO: 80)



ACCAGGGGGAAAACGAAGTGGTGACTCAAATCATCGAAGACCCTCGAGATTACATAGGTCCGGAACC






TATGGCCTTCGTGACCGACCTCGAGTCAGAGTAGTTCAATAAGGACCTATCAAGTTTGGGCAATTTTTC





GTCCCCGACACAAAAATGTCATCCGTGCTTAAAGCATATGAGCGATTCACACTCACTCAAGAACTGCA





AGATCAGAGTGAGGAAGGTACAATCCCACCTACAACACTAAAACCGGTAATCAGGGTATTTATACTAA





CCTCTAATAACCCAGAGCTAAGATCCCGGCTTCTTCTATTCTGCCTACGGATTGTTCTCAGTAATGGTG





CAAGGGATTCCCATCGCTTTGGAGCATTACTTACAATGTTTTCGCTACCATCAGCCACAATGCTCAATC





ATGTCAAATTAGCTGACCAGTCACCAGAAGCTGATATCGAAAGGGTAGAGATCGATGGCTTTGAGGA





GGGATCATTCCGCTTAATCCCCAATGCTCGTTCAGGTATGAGCCGTGGAGAGATCAATGCCTATGCTG





CACTTGCAGAAGATCTACCTGACACACTAAACCATGCAACACCTTTTGTTGATTCCGAAGTCGAGGGA





ACTGCATGGGATGAGATTGAGACTTTCTTAGATATGTGTTACAGTGTCCTAATGCAGGCATGGATAGT





GACTTGCAAGTGCATGACTGCGCCAGACCAACCTGCTGCTTCTATTGAGAAACGCCTGCAAAAATATC





GTCAGCAAGGCAGGATCAACCCGAGATATCTCCTGCAACCGGAGGCTCGAAGAATAATCCAGAATGT





AATCCGAAAGGGAATGGTGGTCAGACATTTCCTCACCTTTGAACTGCAGCTTGCCCGAGCACAAAGCC





TTGTATCAAATAGGTATTATGCTATGGTAGGGGATGTTGGAAAGTATATAGAGAATTGTGGAATGGGA





GGCTTCTTTTTGACACTAAAATATGCATTAGGAACCAGATGGCCCACACTTGCTTTAGCTGCATTTTCA





GGAGAGCTAACAAAGCTAAAGTCCCTCATGGCATTATACCAGACCCTTGGTGAGCAGGCCCGATATTT





GGCCCTATTGGAGTCACCACATTTGATGGATTTTGCTGCAGCAAACTACCCACTGCTATATAGCTATGC





TATGGGAATAGGCTATGTGTTAGATGTCAACATGAGGAACTACGCTTTCTCCAGATCATACATGAATA





AGACATATTTCCAATTGGGAATGGAAACTGCAAGAAAACAACAGGGTGCAGTTGACATGAGGATGGC





AGAAGATCTCGGTCTAACTCAAGCCGAACGCACCGAGATGGCAAATACACTTGCCAAATTGACCACA





GCAAATCGAGGGGCAGACACCAGGGGAGGAGTCAACCCGTTCTCATCTATCACTGGGACAACTCAGG





TGCCCGCTGCAGCAACAGGTGACACATTCGAGAGTTACATGGCAGCGGATCGACTGAGGCAGAGATA





TGCTGATGCAGGCACCCACGATGATGAGATGCCACCATTGGAAGAGGAGGAAGAGGACGACACATCT





GCAGGTCCACGCACTGGACTAACTCTTGAACAAGTGGCCTTGGACATCCAGAACGCAGCAGTTGGAGC





TCCCATCCATACAGATGACCTGAATGCCGCACTGGGTGATCTTGACATCTAGACAATTCAGATCCCAA





TCTTAAATCGACACACCTAATTGACCAGTTAGATGGAACTACAGTGGATTCCATAAGGTTCCTGCCTAC





CATCGGCTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACAAGCGACTGCCGATGCCAATAACA





CAATCCACAATCTACAATGGATCCCACTGATCTGAGCTTCTCCCCAGATGAGATCAATAAGCTCATAG





AGACAGGCCTGAATACTGTGGAGTATTTTACTTCCCAACAAGTCACAGGAACATCCTCTCTTGGAAAG





AATACAATACCACCAGGGGTCACAGGACTACTAACCAATGCTGCAGAGGCAAAGATCCAAGAGTCAA





CCAACCATCAGAAGGGTTCAGTTGGTGGGGGCGCAAAACCAAAGAAACCGCGACCAAAAATTGCCAT





TGTGCCAGCAGATGACAAAACGGTGCCCGGAAAGCCGATCCCAAACCCTCTATTAGGTCTGGACTCCA





CCCCGAGCACCCAAACTGTGCTTGATCTAAGTGGGAAAACATTACCATCAGGATCCTATAAGGGGGTT





AAACTTGCGAAATTTGGAAAAGAAAATCTGATGACACGGTTCATCGAGGAACCCAGAGAGAATCCTA





TCGCAACCAATTCCCCCATCGATTTTAAGAGGGGCAGGGATACCGGCGGGTTCCATAGAAGGGAGTAC





TCAATCGGATGGGTGGGAGATGAAGTCAAGGTCACTGAGTGGTGCAATCCATCCTGTTCTCCAATCAC





CGCTGCAGCAAGGCGATTTGAATGCACTTGTCACCAGTGTCCAGTCACTTGCTCTGAATGTGAACGAG





ATACTTAATACAGTGAGAAATTTGGACTCTCGGATGAATCAACTGGAGACAAAAGTAGATCGCATTCT





CTCATCTCAGTCTCTAATCCAGACCATCAAGAATGACATAGTTGGACTTAAAGCAGGGATGGCTACTT





TAGAAGGAATGATTACAACTGTGAAAATCATGGACCCGGGAGTTCCCAGTAATGTTACTGTGGAAGAT





GTACGCAAGAAACTAAGTAACCATGCTGTTGTTGTGCCAGAATCATTCAATGATAGTTTCTTGACTCAA





TCTGAAGATGTAATTTCACTTGATGAGTTGGCTCGACCAACTGCAACAAGTGTTAAGAAGATTGTCAG





GAAGGTTCCTCCTCAGAAGGATCTGACTGGATTGAAGATCACACTAGAGCAATTGGCAAAGGATTGCA





TCAGCAAACCGAAGATGAGGGAAGAGTATCTCCTCAAAATCAACCAGGCTTCCAGTGAGGCTCAGCT





AATTGACCTCAAGAAAGCAATCATCCGCAGTGCAATTTGATCAAGAAACACCCAATTACACTACACTG





GTATGACACTGTACTAACCCTGAGGGTTTTAGAAAAAACGATTAACGATAAATAAGCCCGAACACTAC





ACACCACCCGAGGCAGCCATGCCATCCATCAGCATCCCCGCAGACCCCACCAATCCACGTCAATCAAT





AAAAGCGTTCCCAATTGTGATCAACCGTGATGGGGGTGAGAAAGGTCGCTTGGTTAAACAACTACGCA





CAACCTACTTGAATGACCTAGATACTCATGAGCCACTGGTGACATTCGTAAATACTTATGGATTCATCT





ACGAACAGGATCGGGGAAATACCATTGTCGGAGAGGATCAACATGGGAAGAAAAGAGAGGCTGTGA





CTGCTGCAATGGTTACCCTTGGATGTGGGCCTAATCTACCATCATTAGGGAATGTCCTGGGACAACTG





AGTGAATTCCAGGTCATTGTTAGGAAGACATCCAGCAAAGCGGAAGAGATGGTCTTTGAAATTGTTAA





GTATCCGAGAATATTTCGGGGTCATACATTAATCCAGAAAGGACTAGTCTGTGTCTCCGCAGAAAAAT





TTGTTAAGTCACCAGGGAAAGTACAATCTGGAATGGACTATCTCTTCATTCCGACATTTCTGTCAGTGA





CTTACTGTCCAGCTGCAATCAAATTTCAGGTACCTGGCCCCATGTTGAAAATGAGATCAAGATACACT





CAGAGCTTACAACTTGAACTAATGATAAGAATCCTGTGTAAGCCCGATTCGCCACTTATGAAGGTCCA





TATCCCTGACAAGGAAGGAAGAGGATGTCTTGTATCAGTATGGTTGCATGTATGCAATATCTTCAAAT





CAGGAAACAAGAATGGCAGTGAGTGGCAGGAATACTGGATGAGAAAGTGTGCTAACATGCAACTTGA





AGTGTCGATTGCAGATATGTGGGGACCAACTATCATAATTCATGCCAGAGGTCACATTCCCAAAAGTG





CTAAGTTGTTTTTTGGAAAGGGTGGATGGAGCTGCCATCCACTTCACGAAGTTGTTCCAAGTGTCACTA





AAACACTATGGTCCGTGGGCTGTGAGATTACAAAGGCGAAGGCAATAATACAAGAGAGTAGCATCTC





TCTTCTCGTGGAGACTACTGACATCATAAGTCCAAAAGTCAAAATTTCATCTAAGCATCGCCGCTTTGG





GAAATCAAATTGGGGTCTGTTCAAGAAAACCAAATCACTGCCCAACCTGACGGAGCTGGAATGAgctagc





CCTGCTATAGGCTATCCACTGCATCATCTCTTTTTAAGAAAAAAATAGGCCCGGACGGGTTAGCAACA





AGCGACTGCCGGTGCCAACAACACAATCCACAATCTACAGTCGACGCGGCCGCCACCatgttcgtgttc





ctggtgctgctgccactggtcagcagccagtgcgtgaatttcactacccggacccagctgcctcctgctt





atacaaacagcttcaccaggggagtgtactaccccgataaggtgttccgcagctctgtgctgcacagc





acccaggacttgtttcttcccttcttcagcaacgtgacctggttccacgccatccacgtgtccggcac





caacggcaccaaaagattcgccaatcctgtgctgcctttcaacgatggcgtgtactttgcctctac





agagaagtctaacatcatcagaggctggatcttcggcacaaccctggattctaaaacccagagcctg





ctgatcgtgaacaatgccaccaatgtagtgatcaaggtttgtgagttccagttctgcaacgacccctttc





tgggcgtttactaccacaagaacaacaaaagctggatggaaagcgagttcagggtgtactctagcgcca





acaactgtaccttcgagtacgtgagccagccttttctgatggacctggagggcaagcagggcaacttca





aaaacctgcgggagttcgtgtttaagaacatcgacggatacttcaagatttactccaagcacaccccaat





taacttggttagaggactgccccaaggcttcagcgccctggaacccctggtggacctgcctatcgg





catcaacatcacaagattccaaaccctgcatagaagctatctgacaccaggcgactctagctctggat





ggacagccggcgccgctgcttattacgtgggctacctgcagcctagaaccttcctcctgaaatacaac





gagaacggaaccatcaccgacgccgtggactgcgccctggatcctctgagcgagacaaagtgcaccctg





aagtccttcaccgtcgaaaagggcatctaccaaacaagcaacttcagagtgcagcctactgagagcatcg





tgcggtttccaaacatcaccaacctgtgtccttttggcgaggtgttcaacgccacccggttcgcttccgt





gtacgcctggaatagaaagcggatcagcaactgcgtggccgactacagcgtgctgtataatagcgcc





tcattttctacttttaaatgttacggcgtgtctcctacaaagctgaacgatctgtgcttcacaaatgt





gtacgccgatagcttcgtgattagaggcgacgaggtgcggcagatcgcccctggccagaccggcaac





atcgctgactacaactacaagctgcctgacgacttcaccggctgtgtgatcgcatggaacagcaata





acctggactctaaggtgggcggaaactacaattacctgtacagactgttcagaaagagcaacctgaagc





ccttcgagagagatatctccacagaaatctatcaggccggatctacaccttgtaatggcgtgaagggctt





caactgctacttccctctgcaatcctacggctttcagcccacatacggcgtgggctaccagccataccgg





gtcgtggtgctgagcttcgagctgctgcacgcccctgccacagtgtgcggccctaagaagagcacc





aatctggtaaagaacaagtgcgtcaacttcaatttcaacggcctgaccgggaccggagtgctgaccg





aaagcaacaagaaattcctgccgttccagcagttcggcagagatatcgccgacaccaccgatgccgt





gcgggacccccagacacttgaaatcctggacatcaccccttgcagttttggcggcgtgtccgtgatca





cacctggaacaaacaccagcaaccaggtggccgtgctgtaccagggcgtcaactgcaccgaggtccc





cgtggccatccacgccgatcagctgacacctacatggcgggtgtactctaccggcagcaacgtgttcca





aaccagagccggctgcctgatcggcgctgagcacgtgaacaacagctacgagtgcgacattcctatcgg





tgctggcatctgcgcctcttaccagacacagacaaacagccccagaagagcgagaagcgtggctagtcag





agcatcatcgcctacaccatgagcctgggcgtggagaacagcgtggcctactctaacaatagcatcgcca





tcccaaccaacttcacaatctctgtgaccacagagatcctgcccgtgtccatgaccaagacatctgtg





gactgcacaatgtatatctgtggcgattctaccgagtgcagcaacctgctgctccagtacggcagcttt





tgtacccagctgaatagagccctgacaggcatcgccgtggagcaggataagaacacacaggaggtgttc





gcccaggtgaagcaaatctacaagaccccccctatcaaggactttggcggcttcaatttttcccagatc





ctgcctgatccatccaagccttctaagcggagctttatcgaggacctgctgttcaacaaggtgacc





ctggccgatgccggcttcatcaagcagtatggcgattgcctgggcgacatcgcagccagggacctg





atctgcgcccagaagtttaatggcctgaccgtgctgccacccctgctgacagatgagatgatcgc





acagtacacaagcgccctgctggccggcaccatcacatccggatggaccttcggcgcaggagccgcc





ctccagatcccctttgccatgcagatggcctataggttcaacggcatcggcgtgacccagaatgtgct





gtacgagaaccagaagctgatcgccaatcagtttaactccgccatcggcaagatccaggacagcctg





tcctctacagccagcgccctgggcaagctccaggatgtggtgaatcagaacgcccaggccctgaata





ccctggtgaagcagctgagcagcaacttcggcgccatctctagcgtgctgaatgacatcctgagccgg





ctggacaaggtggaggcagaggtgcagatcgaccggctgatcaccggccggctccagagcctccagacct





atgtgacacagcagctgatcagggccgccgagatcagggccagcgccaatctggcagcaaccaagatgtc





cgagtgcgtgctgggccagtctaagagagtggacttttgtggcaagggctatcacctgatgtccttcc





ctcagtctgccccacacggcgtggtgtttctgcacgtgacctacgtgcccgcccaggagaagaac





ttcaccacagcccctgccatctgccacgatggcaaggcccactttccaagggagggcgtgttcgtg





tccaacggcacccactggtttgtgacacagcgcaatttctacgagccccagatcatcaccacaga





caacaccttcgtgagcggcaactgtgacgtggtcatcggcatcgtgaacaataccgtgtatgatc





cactccagcccgagctggacagctttaaggaggagctggataagtatttcaagaatcacacctcccc





tgacgtggatctgggcgacatcagcggcatcaatgcctccgtggtgaacatccagaaggagatcgac





cgcctgaacgaggtggctaagaatctgaacgagagcctgatcgacctccaggagctgggcaagtatga





gcagtacatcaagtggccctggtacatctggctgggcttcatcgccggcctgatcgccatcgtgatggt





gaccatcatgctgtgctgtatgacatcctgctgttcttgcctgaagggctgctgtagctgtggctcctg





ctgtAAGTTATTGACCATTGTCGTTGCTAATCGAAATAGAATGGAGAATTTTGTTTATCATAAATGACGT





ACGAGGCAGAAGCCTCCAGGTCTGACCCAGCCAATCAAAGCATTATACCAGACCATGGAATGCATAC





CAAACATTATTGACACTAATGACACACAAAATTGGTTTTAAGAAAAACCAAGAGAACAATAGGCCAG





AATGGCTGGGTCTCGGGAGATATTACTCCCTGAAGTCCATCTCAATTCACCAATTGTAAAGCATAAGC





TATACTATTACATTCTACTTGGAAACCTCCCAAATGAGATCGACATTGACGATTTAGGTCCATTACATA





ATCAAAATTGGAATCAAATAGCACATGAAGAGTCTAACTTAGCCCAACGCTTGGTAAATGTAAGAAAT





TTTCTAATTACCCACATCCCTGATCTTAGAAAGGGCCATTGGCAAGAGTATGTCAATGTAATACTGTGG





CCGCGAATTCTTCCCTTGATCCCGGATTTTAAAATCAATGACCAATTGCCTCTACTCAAAAATTGGGAC





AAGTTAGTTAAAGAATCATGTTCAGTAATCAATGCGGGTACTTCCCAGTGCATTCAGAATCTCAGCTAT





GGACTGACAGGTCGTGGGAACCTCTTTACACGATCACGTGAACTCTCTGGTGACCGCAGGGATATTGA





TCTTAAGACGGTTGTGGCAGCATGGCATGACTCAGACTGGAAAAGAATAAGTGATTTTTGGATTATGA





TCAAATTCCAGATGAGACAATTAATTGTTAGGCAAACAGATCATAATGATCCTGATTTAATCACGTAT





ATCGAAAATAGAGAAGGCATAATCATCATAACCCCTGAACTGGTAGCATTATTTAACACTGAGAATCA





TACACTAACATACATGACCTTTGAAATTGTACTGATGGTTTCAGATATGTACGAAGGTCGTCACAACAT





TTTATCACTATGCACAGTTAGCACTTACCTGAATCCTCTGAAGAAAAGAATAACATATTTATTGAGCCT





TGTAGATAACTTAGCTTTTCAGATAGGTGATGCTGTATATAACATAATTGCTTTGCTAGAATCCTTTGT





ATATGCACAGTTGCAAATGTCAGATCCCATCCCAGAACTCAGAGGACAATTCCATGCATTCGTATGTT





CTGAGATTCTTGATGCACTAAGGGGAACTAATAGTTTCACCCAGGATGAATCAAGAACTGTGACAACC





AATTTGATATCCCCATTCCAAGATCTGACCCCAGATCTTACGGCTGAATTGCTCTGTATAATGAGGCTT





TGGGGACACCCCATGCTCACCGCCAGTCAAGCTGCGGGAAAGGTACGCGAGTCCATGTGTGCTGGAA





AAGTATTAGACTTTCCCACCATTATGAAAACACTAGCCTTTTTCCATACTATTCTGATCAATGGATACA





GGAGGAAGCATCATGGAGTATGGCCACCCTTAAACTTACCGGGTAATGCTTCAAAGGGTCTCACGGAA





CTTATGAATGACAATACTGAGATAAGCTATGAATTCACACTTAAGCATTGGAAGGAAATCTCTCTTAT





AAAATTCAAGAAATGTTTTGATGCAGACGCAGGTGAGGAACTCAGTATATTTATGAAAGATAAAGCA





ATTAGTGCCCCAAAACAAGATTGGATGAGTGTGTTTAGAAGAAGCCTAATCAAACAGCGCCATCAGCA





TCATCAGGTCCCCCTACCAAATCCATTCAATCGACGGCTATTGCTAAACTTTCTCGGAGATGACAAATT





CGACCCGAATGTGGAGCTACAGTATGTAACATCAGGTGAGTATCTACATGATGACACGTTTTGTGCAT





CATATTCACTAAAAGAGAAGGAAATTAAACCTGATGGTCGAATTTTTGCAAAGTTGACTAAGAGAATG





AGATCATGTCAAGTTATAGCAGAATCTCTTTTAGCGAACCATGCTGGGAAGTTAATGAAAGAGAATGG





TGTTGTGATGAATCAGCTATCATTAACAAAATCACTATTAACAATGAGTCAGATTGGAATAATATCCG





AGAAAGCTAGAAAATCGACTCGAGATAACATAAATCAACCTGGTTTCCAGAATATCCAGAGAAATAA





ATCACATCACTCCAAGCAAGTCAATCAGCGAGATCCAAGTGATGACTTTGAATTGGCAGCATCTTTTTT





AACTACTGATCTCAAAAAATATTGTTTACAATGGAGGTACCAGACAATTATCCCATTTGCTCAATCATT





AAACAGAATGTATGGTTATCCTCATCTCTTTGAGTGGATTCACTTACGGCTAATGCGTAGTACACTTTA





CGTGGGGGATCCCTTCAACCCACCAGCAGATACCAGTCAATTTGATCTAGATAAAGTAATTAATGGAG





ATATCTTCATTGTATCACCCAGAGGTGGAATTGAAGGGCTATGTCAAAAGGCTTGGACAATGATATCT





ATCTCTGTGATAATTCTATCTGCCACAGAGTCTGGCACACGAGTAATGAGTATGGTGCAGGGAGATAA





TCAAGCAATTGCTGTCACCACACGAGTACCAAGGAGCCTGCCGACTCTTGAGAAAAAGACTATTGCTT





TTAGATCTTGTAATCTATTCTTTGAGAGGTTAAAATGTAATAATTTTGGATTAGGTCACCATTTGAAAG





AACAAGAGACTATCATTAGTTCTCACTTCTTTGTTTATAGCAAGAGAATATTCTATCAGGGGAGGATTC





TAACGCAAGCCTTAAAAAATGCTAGTAAGCTCTGCTTGACAGCTGATGTCCTAGGAGAATGTACCCAA





TCATCATGTTCTAATCTTGCAACTACTGTCATGAGGTTAACTGAGAATGGTGTTGAAAAAGATATCTGT





TTCTACTTGAATATCTATATGACCATCAAACAGCTCTCCTATGATATCATCTTCCCTCAAGTGTCAATTC





CTGGAGATCAGATCACATTAGAATACATAAATAATCCACACCTGGTATCACGATTGGCTCTTCTGCCAT





CCCAGCTAGGAGGTCTAAACTACCTGTCATGCAGTAGGCTGTTCAATCGAAACATAGGCGACCCGGTG





GTTTCCGCAGTTGCAGATCTTAAGAGATTAATTAAATCAGGATGTATGGATTACTGGATCCTTTATAAC





TTATTAGGGAGAAAACCGGGAAACGGCTCATGGGCTACTTTAGCAGCTGACCCGTACTCAATCAATAT





AGAGTATCAATACCCCCCAACTACAGCTCTTAAGAGGCACACCCAACAAGCTCTGATGGAACTCAGTA





CGAATCCAATGTTACGTGGCATATTCTCTGACAATGCACAGGCAGAAGAAAATAATCTTGCTAGATTT





CTCCTGGATAGGGAGGTGATCTTTCCGCGTGTAGCTCACATCATCATTGAGCAAACCAGTGTCGGGAG





GAGAAAACAGATTCAAGGATATTTGGATTCAACTAGATCGATAATGAGTAAATCACTAGAAATTAAGC





CCTTGTCCAATAGGAAGCTTAATGAAATACTGGATTACAACATCAATTACCTAGCTTACAATTTGGCAT





TACTCAAGAATGCTATTGAACCTCCGACTTATTTGAAAGCAATGACTCTTGAAACATGTAGCATCGAC





ATTGCAAGGAGCCTCCGGAAGCTCTCCTGGGCCCCACTCTTGGGTGGGAGAAATCTTGAAGGATTAGA





GACGCCAGATCCCATTGAAATTACTGCAGGAGCATTAATTGTTGGATCGGGCTACTGTGAACAGTGTG





CTGCAGGAGACAATCGATTCACATGGTTTTTCTTGCCATCTGGTATCGAGATAGGAGGGGATCCCCGT





GATAATCCTCCTATCCGTGTACCGTACATTGGCTCCAGGACTGATGAGAGGAGGGTAGCCTCAATGGC





ATACATCAGGGGTGCCTCGAGTAGCCTAAAAGCAGTTCTTAGACTGGCGGGAGTGTACATCTGGGCAT





TCGGAGATACTCTGGAGAATTGGATAGATGCACTGGATTTGTCTCACACTAGAGTTAACATCACACTT





GAACAGCTGCAATCCCTCACCCCACTTCCAACCTCTGCCAATCTAACCCATCGGTTGGATGATGGCAC





AACTACCCTAAAGTTTACTCCTGCGAGCTCTTACACCTTTTCAAGTTTCACTCATATATCAAATGATGA





GCAATACCTGACAATTAATGACAAAACTGCAGATTCAAATATAATCTACCAACAGTTAATGATCACTG





GACTCGGAATTTTAGAAACATGGAATAATCCCCCAATCAATAGAACATTCGAAGAATCTACCCTACAT





TTGCACACTGGTGCATCATGTTGTGTCCGACCTGTGGACTCCTGCATCATCTCAGAAGCATTAACAGTC





AAGCCACATATTACAGTACCGTACAGCAATAAATTTGTATTTGATGAAGACCCGCTATCTGAATATGA





GACTGCAAAACTGGAATCGTTATCATTTCAAGCCCAATTAGGCAACATTGATGCTGTAGATATGACAG





GTAAATTAACATTATTGTCCCAATTCACTGCAAGGCAGATTATTAATGCAATCACTGGACTCGATGAGT





CTGTCTCTCTTACTAATGATGCCATTGTTGCATCAGACTATGTCTCCAATTGGATTAGTGAATGCATGT





ATACCAAATTAGATGAATTATTTATGTATTGTGGGTGGGAACTACTATTGGAACTATCCTATCAAATGT





ATTATCTGAGGGTAGTTGGGTGGAGTAATATAGTGGATTATTCTTACATGATCTTGAGAAGAATCCCG





GGTGCAGCATTAAACAATCTGGCATCTACATTAAGTCATCCAAAACTTTTCCGACGAGCTATCAACCT





AGATATAGTTGCCCCCTTAAATGCTCCTCATTTTGCATCTCTGGACTACATCAAGATGAGTGTGGATGC





AATACTCTGGGGCTGTAAAAGAGTCATCAATGTGCTCTCCAATGGAGGGGACTTAGAATTAGTTGTGA





CATCTGAAGATAGCCTTATTCTCAGTGACCGATCCATGAATCTCATTGCAAGGAAATTAACTTTATTAT





CACTGATTCACCATAATGGTTTGGAACTACCAAAGATTAAGGGGTTCTCTCCTGATGAGAAGTGTTTCG





CTTTGACAGAATTTTTGAGGAAAGTGGTGAACTCAGGGTTGAGTTCAATAGAGAACCTATCAAATTTT





ATGTACAATGTGGAGAACCCACGGCTTGCAGCATTCGCCAGCAACAATTACTACCTGACCAGAAAATT





ATTGAATTCAATACGAGATACTGAGTCGGGTCAAGTAGCAGTCACCTCATATTATGAATCATTAGAAT





ATATTGATAGTCTTAAGCTAACCCCACATGTGCCTGGTACCTCATGCATTGAGGATGATAGTCTATGTA





CAAATGATTACATAATCTGGATCATAGAGTCTAATGCAAACTTGGAGAAGTATCCAATTCCAAATAGC





CCTGAGGATGATTCCAATTTCCATAACTTTAAGTTGAATGCTCCATCGCACCATACCTTACGCCCATTA





GGGTTGTCATCAACTGCTTGGTATAAGGGTATAAGCTGTTGCAGGTACCTTGAGCGATTAAAGCTACC





ACAAGGTGATCATTTATATATTGCAGAAGGTAGTGGTGCCAGTATGACAATCATAGAATACCTATTCC





CAGGAAGAAAGATATATTACAATTCTTTATTTAGTAGTGGTGACAATCCCCCACAAAGAAATTATGCA





CCAATGCCTACTCAGTTCATTGAGAGTGTCCCATACAAGCTCTGGCAAGCACACACAGATCAATATCC





CGAGATTTTTGAGGACTTCATCCCTCTATGGAACGGAAATGCCGCCATGACTGACATAGGAATGACAG





CTTGTGTAGAATTCATCATCAATCGAGTCGGCCCAAGGACTTGCAGTTTAGTACATGTAGATTTGGAAT





CAAGTGCAAGCTTAAATCAACAATGCCTGTCAAAGCCGATAATTAATGCTATCATCACTGCTACAACT





GTTTTGTGCCCTCATGGGGTGCTTATTCTGAAATATAGTTGGTTGCCATTTACTAGATTTAGTACTTTGA





TCACTTTCTTATGGTGCTACTTTGAGAGAATCACTGTTCTTAGGAGCACATATTCTGGTCCAGCTAATC





ATGAGGTTTATTTAATTTGTATCCTTGCCAACAACTTTGCATTCCAGACTGTCTCGCAGGCAACAGGAA





TGGCGATGACTTTAACCGATCAAGGGTTTACTTTGATATCACCTGAAAGAATAAATCAGTATTGGGAT





GGTCACTTGAAGCAAGAACGTATCGTAGCAGAAGCAATTGATAAGGTGGTTCTAGGAGAAGATGCTCT





ATTCAATTCGAGTGATAATGAATTAATTCTCAAATGTGGAGGGACACCAAATGCACGGAATCTTATCG





ATATCGAGCCAGTCGCAACTTTCATAGAATTTGAACAACTGATCTGCACAATGTTGACAACCCACTTG





AAGGAAATAATTGATATAACAAGGTCTGGAACCCAGGATTATGAAAGTTTATTACTCACTCCTTACAA





TTTAGGTCTTCTTGGTAAAATCAGTACGATAGTGAGATTATTAACAGAAAGGATTCTAAATCATACTAT





CAGGAATTGGTTGATCCTCCCACCTTCGCTCCGGATGATCGTGAAGCAGGACTTGGAATTCGGCATATT





CAGGATTACTTCCATCCTCAATTCTGATCGGTTCCTGAAGCTTTCTCCAAATAGGAAATACTTGATTAC





ACAATTAACTGCAGGCTACATTAGGAAATTGATTGAGGGGGATTGTAATATCGATCTAACCAGACCTA





TCCAAAAACAAATCTGGAAAGCATTAGGTTGTGTAGTCTATTGTCACGATCCAGTAGATCAAAGGGAA





TCAACAGAGTTTATTGATATAAATATTAATGAAGAAATAGACCGCGGGATCGATGGCGAGGAAATCTA





AATATATCAAGAATCAGAATTAGTTTAAGAAAAAAGAAGAGGATTAATCTTGGTTTTCCCCTTGGT.






C. Methods of Making

Also included in the present invention are methods of making and using PIV5 viral expression vectors, including, but not limited to any of those described herein.


For example, the present invention includes methods of expressing a coronavirus S protein, including but not limited to the S protein of SARS-CoV-2, in a cell by contacting or infection the cell with a PIV5 viral expression vector, viral particle, or composition as described herein.


The present invention includes methods of inducing an immune response in a subject to a coronavirus S protein, including but not limited to the S protein of SARS-CoV-2, by administering a viral expression vector, viral particle, or composition as described herein to the subject. The immune response may include a humoral immune response and/or a cellular immune response. The immune response may enhance an innate and/or adaptive immune response.


The present invention includes methods expressing a heterologous coronavirus S protein, including but not limited to the S protein of SARS-CoV-2, in a subject by administering a viral expression vector, viral particle, or composition as described herein to the subject.


The present invention includes methods expressing a heterologous coronavirus S protein, including but not limited to the S protein of SARS-CoV-2 alpha, gamma, delta, and omicron strains, in a subject by administering a viral expression vector, viral particle, or composition as described herein to the subject.


D. Methods of Treatment

The disclosure can be used in gene therapy and/or therapeutic approaches for the treatment of disease which involve the increase or decrease of a nucleotide sequence of interest in a host-cell. In these embodiments, the expressible heterologous nucleotide sequence may be derived from a mammalian genome. It may be particularly useful in some embodiments to have the expressible heterologous nucleotide sequence derived from a human genome, wherein expression of the wild-type RNA and/or protein can produce therapeutic effects in a patient. For example, the expressible heterologous nucleotide sequence can encode CFTR, NeuroD1, Cas9 and Guide RNAs, or any other such sequence. In other embodiments, the heterologous nucleotide sequence encodes a secreted protein.


In other embodiments, the expressible heterologous nucleotide sequence responds to positive selection stimuli. In other embodiments, the expressible heterologous nucleotide sequence also responds to negative selection stimuli. In further embodiments, it may be useful for the polynucleotide sequences to further comprise a reporter gene. For example, the report gene can be a luciferase or green fluorescent protein.


In some embodiments, AVLP expresses one or more nucleotide sequences (e.g., siRNAs) that modify the translation and/or transcription of a host-cell nucleotide sequence of interest within a host cell. In some embodiments, transcription and/or translation of the expressible heterologous nucleotide sequence is modified so that its nucleotide sequence is codon degenerated with respect to the endogenous gene in a cell. Additionally, the expressible heterologous nucleotide sequence can be modified so that it co-expresses inhibitory or silencing sequences capable of inhibiting or silencing a host-cell nucleotide sequence of interest within a host cell.


In other embodiments, the expressible heterologous nucleotide of interest generates a product that stabilizes host-cell RNA nucleotide sequences. Such a product can be inducible or continually expressed. For example, the 3′ RhoB untranslated region (UTR) can stabilize target RNAs that express either toxic proteins or other proteins of interest in response to serum. Another example is linking the eotaxin 3′ untranslated region to the target gene of interest, which normally has a low half-life, but is stabilized with the addition of TNF-alpha and IL-4 to the cells. Alternatively, sequences contained in 16 mer sequence in the 5′ coding region of CYP2E 1 and CYP2B 1 mRNA destabilizes target RNAs in the presence of insulin. Upon the removal of insulin the target RNAs are stabilized and the proteins can be expressed (Trong et al., Biochem J., Dec. 23, 2004).


Further non-limiting examples of expressible heterologous sequences that can be used in the invented compositions and methods include sequences can produce proteins, including, for example, e.g., interferons (alpha, beta, gamma, epsilon), erythropoietin, Factor VIII, clotting factors, antibodies and fragments thereof (e.g., including single chain, Fab, and humanized), insulin, chemokines, cytokines, growth factors, angiogenesis modulatory factors, apoptosis modulatory factors, e.g., Growth Factors, including, e.g., Amphiregulin, B-lymphocyte stimulator, Interleukin 16 (IL16), Thymopoietin, TRAIL, Apo-2, Pre B cell colony enhancing factor, Endothelial differentiation-related factor 1 (EDF1), Endothelial monocyte activating polypeptide II, Macrophage migration inhibitory factor MIF, Natural killer cell enhancing factor (NKEFA), Bone morphogenetic protein 8 (osteogenic protein 2), Bone morphogenic protein 6, Connective tissue growth factor (CTGF), CGI-149 protein (neuroendocrine differentiation factor), Cytokine A3 (macrophage inflammatory protein 1-alpha), Glialblastoma cell differentiation-related protein (GBDR1), Hepatoma-derived growth factor, Neuromedin U-25 precursor, any tumor gene, oncogene, proto-oncogene or cell modulating gene (which can be found at condor.bcm.tmc.edu/oncogene), Vascular endothelial growth factor (VEGF), Vascular endothelial growth factor B (VEGF-B), T-cell specific RANTES precursor, Thymic dendritic cell-derived factor 1; Receptors, such as Activin A receptor, type II (ACVR2), β-signal sequence receptor (SSR2), CD14 monocyte LPS receptor, CD36 (collagen type 1/thrombospondin receptor)-like 2, CD44R (Hermes antigen gp90 homing receptor), G protein coupled receptor 9, Chemokine CXC receptor 4, Colony stimulating factor 2 receptor β(CSF2RB), FLT-3 receptor tyrosine kinase, Similar to transient receptor potential C precursor, Killer cell lectin-like receptor subfamily B, Low density lipoprotein receptor gene, low-affinity Fc-gamma receptor IIC, MCP-1 receptor, Monocyte chemoattractant protein 1 receptor (CCR2), Nuclear receptor subfamily 4, group A, member 1, Orphan G protein-coupled receptor GPRC5D, Peroxisome proliferative activated receptor gamma, Pheromore related-receptor (rat), Vasopressin-activated calcium mobilizing putative receptor, Retinoic×receptor, Toll-like receptor 6, Transmembrane activator and CAML interactor (TACI), B cell maturation peptide (BCMA), CSF-1 receptor, Interferon (α, β and gamma) receptor 1 (IFNAR1). Pathways that can be modulated to increase antibody production include, e.g., ubiquitin/proteosome; telomerase; FGFR3; and Mcd-1, etc.


In certain embodiments of the disclosure, AVLP compositions can be utilized to prepare antigenic preparations that be used as vaccines. Any suitable antigen(s) can be prepared in accordance with the disclosure, including antigens obtained from prions, viruses, mycobacterium, protozoa (e.g., Plasmodium falciparum (malaria)), trypanosomes, bacteria (e.g., Streptococcus, Neisseria, etc.), etc.


Host cells can be transfected with single AVLP particles containing one or more heterologous polynucleotide sequences, or with a plurality of AVLP particles, where each comprises the same or different heterologous polynucleotide sequence(s). For example, a multi-subunit antigen (including intracellular and cell-surface multi-subunit components) can be prepared by expressing the individual subunits on separate vectors, but infecting the same host cell with all the vectors, such that assembly occurs within the host cell.


Vaccines often contain a plurality of antigen components, e.g., derived from different proteins, and/or from different epitopic regions of the same protein. For example, a vaccine against a viral disease can comprise one or more polypeptide sequences obtained from the virus which, when administered to a host, elicit an immunogenic or protective response to viral challenge.


As mentioned, the disclosure can also be utilized to prepare polypeptide multimers, e.g., where an antigenic preparation is produced which is comprised of more than one polypeptide. For instance, virus capsids can be made up of more than one polypeptide subunit. By transducing a host cell with vectors carrying different viral envelope sequences, the proteins, when expressed in the cell, can self-assemble into three-dimensional structures containing more than one protein subunit (e.g., in their native configuration).


In further embodiments, the expressible heterologous nucleotide sequence is derived from another virus, other than PIV5. For example, the heterologous nucleotide sequence may encode (from any strain) influenza HA, RSV F, HIV Gag and/or Env, etc. Such embodiments can be useful for developing vaccines and/or methods of vaccination. The examples given here are non-limiting, as it will be understood by those in the art that nucleotide sequences from a variety of pathogenic agents (including also bacteria, parasites, etc.) may be desirable to use for an AVLP vaccine composition and/or method of vaccination.


Examples of viruses to which vaccines can be produced in accordance with the disclosure include, e.g., coronaviruses, orthomyxoviruses, influenza virus A (including all strains varying in their HA and NA proteins, such as (non-limiting examples) H1N1, H1N2, H2N2, H3N2, H7N7, and H3N8); influenza B, influenza C, thogoto virus (including Dhori, Batken virus, SiAR 126 virus), and isavirus (e.g., infectious salmon anemia virus) and the like. These include coronaviruses isolated or transmitted from all species types, including isolates from invertebrates, vertebrates, mammals, humans, non-human primates, monkeys, pigs, cows, and other livestock, birds, domestic poultry such as turkeys, chickens, quail, and ducks, wild birds (including aquatic and terrestrial birds), reptiles, etc. These also include existing strains which have changed, e.g., through mutation, antigenic drift, antigenic shift, recombination, etc., especially strains which have increased virulence and/or interspecies transmission (e.g., human-to-human).


E. Methods of Administration

I. Administration by Vaccination


The present invention includes methods of vaccinating a subject by administering a viral expression vector, viral particle, or composition as described herein to the subject.


The disclosure provides vaccines against all coronaviruses, including existing subtypes, derivatives thereof, and recombinants thereof, such as subtypes and recombinants which have the ability to spread from human-to-human. Various isolates have been characterized, especially for SARS-COV-2.


The disclosure also provides methods for producing AVLP compositions. Examples of host cells which can be utilized to produce AVLP compositions, include, any mammalian or human cell line or primary cell. Non-limiting examples include, e.g., 293, HT1080, Jurkat, and SupT1 cells. Other examples are CHO, 293, Hela, Vero, L929, BHK, NIH 3T3, MRC-5, BAE-1, HEP-G2, NSO, U937, Namalwa, HL60, WEHI 231, YAC 1, U 266B1, SH-SY5Y, CHO, e.g., CHO-K1 (CCL-61), 293 (e.g., CRL-1573). Cells are cultured under conditions effective to produce transfection and expression. Such conditions include, e.g., the particular milieu needed to achieve protein production. Such a milieu, includes, e.g., appropriate buffers, oxidizing agents, reducing agents, pH, co-factors, temperature, ion concentrations, suitable age and/or stage of cell (such as, in particular part of the cell cycle, or at a particular stage where particular genes are being expressed) where cells are being used, culture conditions (including cell media, substrates, oxygen, carbon dioxide, glucose and other sugar substrates, serum, growth factors, etc.).


The disclosure also provides various treatment methods involving delivering AVLP to host cells in vivo. In some embodiments, AVLP is delivered into a subject for treating or preventing coronaviruses. In other embodiments, AVLP is delivered into a subject for treating or preventing SARS-COV-2 alpha, delta, omicron strains, or variants thereof or eliciting an immune response to SARS-COV-2 in a subject.


It is contemplated that when used to treat various diseases, the compositions and methods of the disclosure can be combined with other therapeutic agents suitable for the same or similar diseases. Also, two or more embodiments of the disclosure may be also co-administered to generate additive or synergistic effects. When co-administered with a second therapeutic agent, the embodiment of the disclosure and the second therapeutic agent may be simultaneously or sequentially (in any order). Suitable therapeutically effective dosages for each agent may be lowered due to the additive action or synergy.


As a non-limiting example, the disclosure can be combined with other therapies that block inflammation through (e.g., via inhibition, reduction and/or blockage of ILL INFα/β, IL6, TNF, L13, IL23, etc.). In some embodiments, AVLP compositions and methods disclosed herein are useful to enhance the efficacy of vaccines directed to SARS-COV-2 infections. The compositions and methods of the disclosure can be administered to a subject either simultaneously with or before (e.g., 1-30 days before) a reagent (including but not limited to small molecules, antibodies, or cellular reagents) that acts to elicit an immune response (e.g., to treat cancer or an infection). The compositions and methods of the disclosure can be also administered in combination with an anti-tumor antibody or an antibody directed at a pathogenic antigen or allergen.


The pharmaceutical compositions of the invention can be readily employed in a variety of therapeutic or prophylactic applications, e.g., for treating SARS-COV-2 infection or eliciting an immune response to SARS-COV-2 in a subject. In various embodiments, the vaccine compositions can be used for treating or preventing infections caused by a pathogen from which the displayed immunogen polypeptide in the PIV5-based vaccine is derived. Thus, the vaccine compositions of the invention can be used in diverse clinical settings for treating or preventing infections caused by various viruses. As exemplification, a SARS-COV-2 PIV-5-based vaccine composition can be administered to a subject to induce an immune response to SARS-COV-2, e.g., to induce production of broadly neutralizing antibodies to the virus. For subjects at risk of developing an SARS-COV-2 infection, a vaccine composition of the invention can be administered to provide prophylactic protection against viral infection. Therapeutic and prophylactic applications of vaccines derived from the other immunogens described herein can be similarly performed. Depending on the specific subject and conditions, pharmaceutical compositions of the invention can be administered to subjects by a variety of administration modes known to the person of ordinary skill in the art, for example, topical, oral, intranasal, intramuscular, subcutaneous, intravenous, intra-arterial, intra-articular, intraperitoneal, or parenteral routes. In some aspects, administration is to a mucosal surface. A vaccine may be administered by mass administration techniques such as by placing the vaccine in drinking water or by spraying the animals' environment. When administered by injection, the immunogenic composition or vaccine may be administered parenterally. Parenteral administration includes, for example, administration by intravenous, subcutaneous, intramuscular, or intraperitoneal injection.


1. Vaccination by Inhalation


In one embodiment, the disclosed PIV-5 vaccine compositions are formulated to allow intranasal administration. Intranasal compositions may comprise an inhalable dry powder pharmaceutical formulation comprising a therapeutic agent, wherein the therapeutic agent is present as a freebase or as a mixture of a salt and a freebase. Pharmaceutical formulations disclosed herein can be formulated as suitable for airway administration, for example, nasal, intranasal, sinusoidal, peroral, and/or pulmonary administration. Typically, formulations are produced such that they have an appropriate particle size for the route, or target, of airway administration. As such, the formulations disclosed herein can be produced so as to be of defined particle size distribution.


For example, the particle size distribution for a salt form of a therapeutic agent for intranasal administration can be between about 5 μm and about 350 More particularly, the salt form of the therapeutic agent can have a particle size distribution for intranasal administration between about 5μ to about 250 μm, about 10 μm to about 200 μm, about 15 μm to about 150 μm, about 20 μm to about 100 μm, about 38 μm to about 100 μm, about 53 μm to about 100, about 53 μm to about 150 μm, or about 20 μm to about 53 μm. The salt form of the therapeutic agent in the pharmaceutical compositions of the invention can a particle size distribution range for intranasal administration that is less than about 200 μm. In other embodiments, the salt form of the therapeutic agent in the pharmaceutical compositions has a particle size distribution that is less than about 150 μm, less than about 100 μm, less than about 53 μm, less than about 38 μm, less than about 20 μm, less than about 10 μm, or less than about 5 μm. The salt form of the therapeutic agent in the pharmaceutical compositions of the invention can have a particle size distribution range for intranasal administration that is greater than about 5 μm, greater than about 10 μm, greater than about 15 μm, greater than about 20 greater than about 38 μm, less than about 53 μm, less than about 70 μm, greater than about 100 or greater than about 150 μm.


Additionally, the salt form of the therapeutic agent in the pharmaceutical compositions of the invention can have a particle size distribution range for pulmonary administration between about 1 μm and about 10 μm. In other embodiments for pulmonary administration, particle size distribution range is between about 1 μm and about 5 or about 2 μm and about 5 In other embodiments, the salt form of the therapeutic agent has a mean particle size of at least 1 μm, at least 2 μm, at least 3 μm, at least 4 μm, at least 5 μm, at least 10 at least 20 μm, at least 25 μm, at least 30 μm, at least 40 μm, at least 50 μm, at least 60 at least 70 μm, at least 80 μm, at least 90 μm, or at least 100 μm.


In some embodiments the disclosed cannabinoid compositions include one or more cannabinoids or pharmaceutically acceptable derivatives or salts thereof, a propellant, an alcohol, and a glycol and/or glycol ether. The alcohol may be a monohydric alcohol or a polyhydric alcohol, and is preferably a monohydric alcohol. Monohydric alcohol has a lower viscosity than a glycol or glycol ether. Accordingly, the composition is able to form droplets of a smaller diameter in comparison to compositions in which the monohydric alcohol is not present. The present inventors have surprisingly found that a specific ratio of monohydric alcohol to glycol or glycol ether results in a composition with a desired combination of both long term stability (for example the composition remains as a single phase for at least a week at a temperature of 2-40° C.) and small droplet size.


2. Pulmonary Compositions


One embodiment provides a formulation and method for treating SARS-COV-2 in the pulmonary system by inhalation or pulmonary administration. The diffusion characteristics of the particular drug formulation through the pulmonary tissues are chosen to obtain an efficacious concentration and an efficacious residence time in the tissue to be treated. Doses may be escalated or reduced or given more or less frequently to achieve selected blood levels. Additionally, the timing of administration of administration and amount of the formulation is preferably controlled to optimize the therapeutic effects of the administered formulation on the tissue to be treated and/or titrate to a specific blood level.


Diffusion through the pulmonary tissues can additionally be modified by various excipients that can be added to the formulation to slow or accelerate the absorption of drugs into the pulmonary tissues. For example, the drug may be combined with surfactants such as the phospholipids, dimyristoylphosphatidyl choline, and of administration dimyristoylphosphatidyl glycerol. The drugs may also be used in conjunction with bronchodilators that can relax the bronchial airways and allow easier entry of the antineoplastic drug to the lung. Albuterol is an example of the latter with many others known in the art. Further, the drug may be complexed with biocompatible polymers, micelle forming structures or cyclodextrins.


Particle size for the aerosolized drug used in the present examples was measured at about 1.0-5.0 μm with a GSD less than about 2.0 for deposition within the central and peripheral compartments of the lung. As noted elsewhere herein particle sizes are selected depending on the site of desired deposition of the drug particles within the respiratory tract.


Aerosols useful in the invention include aqueous vehicles such as water or saline with or without ethanol and may contain preservatives or antimicrobial agents such as benzalkonium chloride, paraben, and the like, and/or stabilizing agents such as polyethyleneglycol.


Powders useful in the invention include formulations of the neat drug or formulations of the drug combined with excipients or carriers such as mannitol, lactose, or other sugars. The powders used herein are effectively suspended in a carrier gas for administration. Alternatively, the powder may be dispersed in a chamber containing a gas or gas mixture which is then inhaled by the patient.


An agent of the present disclosure may be administered at once or may be divided into a number of multiple doses to be administered at intervals of time. For example, agents of the invention may be administered repeatedly, e.g., at least 2, 3, 4, 5, 6, 7, 8, or more times, or may be administered by continuous infusion. It is understood that the precise dosage and duration of treatment is a function of the disease being treated and may be determined empirically using known testing protocols or by extrapolation from in vivo or in vitro test data. It is to be noted that concentrations and dosage values may also vary with the severity of the condition to be alleviated. It is to be further understood that for any particular subject, specific dosage regimens should be adjusted over time according to the individual need and the professional judgment of the person administering or supervising the administration of the compositions, and that any concentration ranges set forth herein are exemplary only and are not intended to limit the scope or practice of the claimed compositions and methods.


In some therapeutic embodiments, an “effective amount” of an agent is an amount that results in a reduction of at least one pathological parameter. Thus, for example, in some aspects of the present disclosure, an effective amount is an amount that is effective to achieve a reduction of at least about 10%, at least about 15%, at least about 20%, or at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, or at least about 95%, compared to the expected reduction in the parameter in an individual not treated with the agent.


In some aspects, any of the PIV5-based constructs and methods described in WO 2013/112690 and WO 2013/112720 (which is hereby incorporated by reference herein in its entirety) may be used in the present invention.


As used herein, the term “subject” represents an organism, including, for example, a mammal. A mammal includes, but is not limited to, a human, a non-human primate, and other non-human vertebrates. A subject may be an “individual,” “patient,” or “host.” Non-human vertebrates include livestock animals (such as, but not limited to, a cow, a horse, a goat, and a pig), a domestic pet or companion animal, such as, but not limited to, a dog or a cat, and laboratory animals. Non-human subjects also include non-human primates as well as rodents, such as, but not limited to, a rat or a mouse. Non-human subjects also include, without limitation, poultry, horses, cows, pigs, goats, dogs, cats, guinea pigs, hamsters, mink, and rabbits.


As used herein “in vitro” is in cell culture and “in vivo” is within the body of a subject. As used herein, “isolated” refers to material that has been either removed from its natural environment (e.g., the natural environment if it is naturally occurring), produced using recombinant techniques, or chemically or enzymatically synthesized, and thus is altered “by the hand of man” from its natural state.


I. Booster Vaccines


The present disclosure provides for the administration of a booster PIV-5 vaccine for use in such a method for inducing in a human subject an immune response, wherein said subject has previously received a primary vaccination against SARS-COV-2.


The method of booster vaccination according to the disclosure comprises the step of administering the vaccine composition to the subject.


The immune response induced by the vaccine composition of the disclosure or by the method of the disclosure is preferably a humoral response, especially a response comprising the production of neutralizing antibodies against the COVID-19 virus, i.e. a neutralizing antibody response.


F. Exemplary Embodiments

Exemplary Embodiments of the present disclosure include, but are not limited to, the following.


Embodiment 1: A viral expression vector comprising a parainfluenza virus 5 (PINS) genome having a heterologous nucleic acid sequence with at least 98% sequence identity to SEQ ID NOs: 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, or 80, wherein the viral expression vector expresses a heterologous polypeptide comprising a coronavirus spike (S) and/or nucleocapsid (N) proteins.


Embodiment 2: The viral expression vector of Embodiment 1, wherein the coronavirus S protein is a coronavirus S protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a variant of interest or a variant of concern of SARS-CoV-2 and the coronavirus N protein is the coronavirus N protein of SARS-CoV-2, a variant of interest or a variant of concern of SARS-CoV-2.


Embodiment 3: The viral expression vector of Embodiment 1, wherein the coronavirus S protein is the coronavirus S protein of a SARS-CoV-2 beta variant, a SARS-CoV-2 gamma variant, a SARS-CoV-2 delta variant, or a SARS-CoV-2 omicron variant and the coronavirus N protein is the coronavirus N protein of a SARS-CoV-2 beta variant, a SARS-CoV-2 gamma variant, a SARS-CoV-2 delta variant, or a SARS-CoV-2 omicron variant.


Embodiment 4: The viral expression vector of Embodiment 1, wherein the coronavirus S protein comprises the coronavirus S protein of SARS-CoV-2 and wherein the cytoplasmic tail of the coronavirus S protein has been replaced with the cytoplasmic tail of the fusion (F) protein of PIV5.


Embodiment 5: The viral expression vector of Embodiment 1, wherein the coronavirus S protein of a variant of SARS-CoV-2 has been inserted between the PIV5 small hydrophobic (SH) and hemagglutinin (HN) genes and the coronavirus N protein of a variant of SARS-CoV-2 has been inserted between the PIV5 HN and polymerase (L) genes.


Embodiment 6: The viral expression vector of any one of Embodiments 1, wherein the coronavirus S protein of a variant of SARS-CoV-2 has been inserted between the PIV5 HN and polymerase (L) genes.


Embodiment 7: The viral expression vector of Embodiment 1, wherein the coronavirus S protein is a S protein from a variant of interest or a variant of concern of SARS-CoV-2 and the coronavirus N protein is a N protein from different variant of interest or a variant of concern of SARS-CoV-2.


Embodiment 8: The viral expression vector of Embodiment 1, wherein the PIV5 small hydrophobic (SH) gene has been replaced with the coronavirus N protein of SARS-CoV-2.


Embodiment 9: The viral expression vector of Embodiment 1, wherein the PIV5 genome further comprises one or more mutations comprising a mutation of the V/P gene, a mutation of the shared N-terminus of the V and P proteins, a mutation of residues 26, 32, 33, 50, 102, and/or 157 of the shared N-terminus of the V and P proteins, a mutation lacking the C-terminus of the V protein, a mutation lacking the small hydrophobic (SH) protein, a mutation of the fusion (F) protein, a mutation of the phosphoprotein (P), a mutation of the large RNA polymerase (L) protein, a mutation incorporating residues from canine parainfluenza virus, a mutation inducing apoptosis, or a combination thereof.


Embodiment 10: The viral expression vector of Embodiment 9, wherein the one or more mutations comprise PIV5VΔC, PIV5ΔSH, PIV5-P-S308G, or a combination thereof.


Embodiment 11: The viral expression vector of Embodiment 1, wherein the heterologous polypeptide comprises a CPI V/P gene that contains mutations at amino acid residue S157 or S308, or the combination thereof, wherein serine (S) is substituted with an amino acid residue selected from a group consisting of alanine (A), asparagine (B), cysteine (C), aspartic acid (D), glutamic acid (E), phenylalanine (F), glycine (G), histidine (H), isoleucine (I), lysine (K), leucine (L), methionine (M), asparagine (N), proline (P), glutamine (Q), arginine (R), selenocysteine (U), valine (V), tryptophan (W), tyrosine (Y), and glutamine (Z).


Embodiment 12: The viral expression vector of Embodiment 11, wherein the amino acid substitution at amino acid residue S157 comprises a substitution of serine (S) to phenylalanine (F) and the amino acid substitution at amino acid residue S308 comprises a substitution of serine (S) to alanine (A) or Glycine (G).


Embodiment 13: The viral expression vector of Embodiment 1, wherein a viral particle comprises the viral expression vector.


Embodiment 14: A composition comprising the viral expression vector of Embodiment 1 or the viral particle of Embodiment 13 or a combination thereof.


Embodiment 15: The composition of Embodiment 14, wherein a heterologous coronavirus spike (S) and nucleocapsid (N) proteins are expressed in a cell by contacting the cell with the composition.


Embodiment 16: A method of inducing an immune response in a subject having coronavirus disease 2019 (COVID-19) to coronavirus spike (S) and nucleocapsid (N) proteins, the method comprising administering the composition of Embodiment 14 to the subject, wherein the immune response comprises a humoral immune response and/or a cellular immune response.


Embodiment 17: The method of Embodiment 16, wherein the subject is vaccinated against COVID-19), the method comprising administering the composition to the subject.


Embodiment 18: The method of Embodiment 16, wherein the composition is administered intranasally, intramuscularly, topically, or orally.


Embodiment 19: A method of inducing in a subject an immune response comprising administering a PIV-5 booster vaccine composition comprising a viral expression vector or a viral particle having a PIV5 genome comprising a heterologous nucleic acid sequence with at least 98% sequence identity to SEQ ID NOs: 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, or 80, wherein said subject has previously received a primary vaccination against SARS-COV-2.


The term “and/or” means one or all of the listed elements or a combination of any two or more of the listed elements.


The words “preferred” and “preferably” refer to embodiments of the invention that may afford certain benefits, under certain circumstances. However, other embodiments may also be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful and is not intended to exclude other embodiments from the scope of the invention.


The terms “comprises” and variations thereof do not have a limiting meaning where these terms appear in the description and claims.


Unless otherwise specified, “a,” “an,” “the,” and “at least one” are used interchangeably and mean one or more than one.


Unless otherwise indicated, all numbers expressing quantities of components, molecular weights, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless otherwise indicated to the contrary, the numerical parameters set forth in the specification and claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.


Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. All numerical values, however, inherently contain a range necessarily resulting from the standard deviation found in their respective testing measurements.


For any method disclosed herein that includes discrete steps, the steps may be conducted in any feasible order. And, as appropriate, any combination of two or more steps may be conducted simultaneously.


The description exemplifies illustrative embodiments. In several places throughout the application, guidance is provided through lists of examples, which examples can be used in various combinations. In each instance, the recited list serves only as a representative group and should not be interpreted as an exclusive list.


All headings are for the convenience of the reader and should not be used to limit the meaning of the text that follows the heading, unless so specified.


The present invention is illustrated by the following examples. It is to be understood that the particular examples, materials, amounts, and procedures are to be interpreted broadly in accordance with the scope and spirit of the invention as set forth herein.


EXAMPLES
Example 1: Vaccine Efficacy Study in a Syrian Hamster SARS-CoV-2 Challenge Model

Materials:


The SARS-CoV-2 vaccine candidates generated are described herein.


CVL34 for CVXGA2: The N gene of SARS-CoV-2 Wuhan strain was amplified by PCR, inserted into CPI containing the S gene of SARS-CoV-2 Wuhan strain by Gibson assembly. The recombinant virus was rescued on 293-T serum free cells, which contains the S gene of SARS-CoV-2 Wuhan strain between SH and HN, the N gene of SARS-CoV-2 Wuhan strain between HN and L of CPI.


CVL44 for CVXGA3: The S gene of SARS-CoV-2 Beta variant was amplified by PCR, inserted into CPI backbone by Gibson assembly. The recombinant virus was rescued on 293-T serum free cells, which contains the S gene of SARS-CoV-2 Beta variant between SH and HN of CPI.


CVL48 for CVXGA4: The S gene of SARS-CoV-2 Alpha variant was digested from a plasmid containing the gene generated from Genscript, inserted into CPI backbone by Gibson assembly. The recombinant virus was rescued on 293-T serum free cells, which contains the S gene of SARS-CoV-2 Alpha variant between SH and HN of CPI.


CVL49 for CVXGA5: The S gene of SARS-CoV-2 Gamma variant was digested from a plasmid containing the gene generated from Genscript, inserted into CPI backbone by Gibson assembly. The recombinant virus was rescued on 293-T serum free cells, which contains the S gene of SARS-CoV-2 Gamma variant between SH and HN of CPI.


CVL50 for CVXGA6: The S gene of SARS-CoV-2 Epsilon variant was amplified by PCR, inserted into CPI backbone by Gibson assembly. The recombinant virus was rescued on Vero serum free cells, which contains the S gene of SARS-CoV-2 Epsilon variant between SH and HN of CPI.


CVL52 for CVXGA7: The N gene of SARS-CoV-2 Wuhan strain was amplified by PCR, inserted into CVL44 backbone by Gibson assembly. The recombinant plasmid contains the N gene of SARS-CoV-2 Wuhan strain and the S gene of SARS-CoV-2 Beta variant between F and HN, and lacking the CPI SH gene. The plasmid construct is being generated.


CVL53 for CVXGA8: The N gene of SARS-CoV-2 Wuhan strain was amplified by PCR, inserted into CPI backbone by Gibson assembly. The recombinant virus was rescued on 293-T serum free cells, which contains the N gene of SARS-CoV-2 Wuhan strain between F and HN, and the SH gene deletion of CPI.


CVL54 for CVXGA9: The S gene of SARS-CoV-2 Beta variant was amplified by PCR, inserted into CVL53 backbone by Gibson assembly. The recombinant plasmid contains the N gene of SARS-CoV-2 Wuhan strain between F and HN, the S gene of SARS-CoV-2 Beta variant between HN and L, and the SH gene deletion of the CPI backbone. The plasmid construct is being generated.


CVL55 for CVXGA10: CPI-V/P gene containing the S157F and S308A mutations (PLK mutations) was amplified by PCR, inserted into CVL44 backbone by Gibson assembly. The recombinant virus was rescued on 293-T serum free cells, which contains the S gene of SARS-CoV-2 Beta variant between SH and HN, and the S157F and S308A mutations in CPI-V/P gene.


CVL58 for CVXGA11: CPI with the SH gene deletion (CPIΔSH) was obtained by PCR amplification and Gibson assembly in CVL44 backbone. The recombinant plasmid containing the S gene of SARS-CoV-2 Beta variant between F and HN, and the CPI SH gene deletion, was obtained. Virus rescue is being rescued.


CVL59 for CVXGA12: CPI lacking SH gene (CPIΔSH) was obtained by PCR amplification and Gibson assembly in CVL55 backbone. The recombinant plasmid has been obtained, which contains the S gene of SARS-CoV-2 Beta variant between F and HN, CPI SH gene deletion, and S157F and S308A mutations in CPI-V/P gene.


CVL60 for CVXGA13: The S gene of SARS-CoV-2 Delta variant was digested from a plasmid containing the gene generated from Genscript, then inserted into CPI backbone by Gibson assembly. The recombinant CVGA13 virus was rescued in Vero serum free Vero cells, which contains the S gene of SARS-CoV-2 Delta variant between SH and HN.


CVL64 for CVXGA26: The S gene of SARS-CoV-2 Lambda variant was digested from a plasmid containing the gene generated in-house, then inserted into CPI backbone by Gibson assembly. The recombinant plasmid contains the S gene of SARS-CoV-2 Lambda variant between SH and HN. The plasmid construct is being generated.


CVL65 for CVXGA27: The S gene of SARS-CoV-2 Delta variant was amplified by PCR and inserted into CVL54 backbone by Gibson assembly. The recombinant virus will contain N gene of SARS-CoV-2 Wuhan strain between F and HN, S gene of SARS-CoV-2 Delta variant between HN and L, and lacking SH gene of CPI backbone. The plasmid DNA construct will be generated.


CVL67 for CVXGA28: The S gene of SARS-CoV-2 Mu variant will be digested from a plasmid containing the gene generated in-house and inserted into CPI backbone by Gibson assembly. The recombinant virus will contain S gene of SARS-CoV-2 Mu variant between SH and HN. The primers have been ordered for making the plasmid construct.


CVL80 for CVXGA14: The S gene of SARS-CoV-2 Omicron BA.1 variant was generated by Genscript, then inserted into CPI backbone by Gibson assembly. The recombinant plasmid contains the S gene of SARS-CoV-2 Omicron BA.1 variant between SH and HN. The recombinant virus is obtained.


CVL86 for CVXGA15: The 5′ end of S gene of SARS-CoV-2 Omicron BA.2 variant was generated by Genscript, 3′ end of S gene was amplified by mutagenesis of the PCR reactions and inserted into CPI backbone by Gibson assembly. The recombinant plasmid contains the S gene of SARS-CoV-2 Omicron BA.2 variant between the SH and HN genes. The recombinant virus rescue is ongoing.


CVL108 for CVXGA20: The S gene of SARS-CoV-2 Omicron BA.5 variant was amplified and inserted into CVL86 backbone to replace the S gene of BA.2 variant by Gibson assembly. The recombinant plasmid contains the S gene of SARS-CoV-2 Omicron BA.5 variant between the SH and HN genes of PIV5. The recombinant virus is obtained.


CVL111 for CVXGA23: The 5′ end of S gene of SARS-CoV-2 Omicron BA.2.75 variant was generated by Genscript, and 3′ end of S gene was amplified from CVL86 plasmid and inserted into CVL6 backbone to replace the S gene of Wuhan strain by Gibson assembly. The recombinant plasmid will contain S gene of SARS-CoV-2 Omicron BA.2.75 variant between the SH and HN genes of PIV5.


CVL113 for CVXGA25: The PIV5 F and HN genes was deleted from CVL54 backbone by Gibson assembly. The recombinant plasmid will contain CPI backbone without F and HN genes, and S gene of SARS-CoV-2 Wuhan strain between HN and L genes of PIV5. The recombinant plasmid construction is ongoing. The recombinant virus will only contain the glycoprotein from the SARS-COV-2 virus. This virus can serve either as the vaccine strain and/or the virus for microneutralization assay to measure S-specific antibody response.


The primers used in cDNA cloning of the CPI-S vaccine candidates are listed in Table 1.









TABLE 1







Primer sequences used in constructing CPI


based COVID-19 S vaccine candidates













SEQ


Con-


ID


struct
Primer
Sequence
NO:





CVL34
oCVL101
ACATTAATGGCATCAATCAGTTCTATT
 1




TCTCAATT




oCVL106
AGATTAGAACATGATGATTGGGTACAT
 2




TCT






CVL44
oCVL119
CGGTGCCAACAACACAATCCACAATCT
 3




ACA




oCVL120
GCTATTGTTAGAGTAGGCCACGCTGTT
 4




CTC




oCVL121
GAGAACAGCGTGGCCTACTCTAACAAT
 5




AGC




oCVL122
ATATGATGTGAGTAGGAAGTATGGCAG
 6




GAG






CVL50
oCVL119
CGGTGCCAACAACACAATCCACAATCT
 7




ACA




oCVL127
GTGAATTGTACCGAGGTGCCCGTGGCT
 8




ATC




oCVL128
GATAGCCACGGGCACCTCGGTACAATT
 9




CAC




oCVL122
ATATGATGTGAGTAGGAAGTATGGCAG
10




GAG






CVL52
oCVL17
CAAGATGCACCTTCTCTCCAGTG
11



oCVL132
GTTCTGTGGTCCGTTATCTGACATGGT
12




GGCGCGCGATTTGAGCTTTCCGAGACG





GTAGC




oCVL133
GCGCGCCACCATGTCAGATAACGGACC
13




ACAGAAC




oCVL134
TCAAGCCTGGGTGGAGTCGGCACTG
14



oCVL135
CAGTGCCGACTCCACCCAGGCTTGACG
15




TACGACCTGCTATAGGCTATCCACTGC





ATC




oCVL124
CAGGCCGTTGAAATTGAAGT
16





CVL53
oCVL17
CAAGATGCACCTTCTCTCCAGTG
17



oCVL132
GTTCTGTGGTCCGTTATCTGACATGGT
18




GGCGCGCGATTTGAGCTTTCCGAGACG





GTAGC




oCVL133
GCGCGCCACCATGTCAGATAACGGACC
19




ACAGAAC




oCVL136
GATATGATGTGAGTAGGAAGTATGGCA
20




GGAGGCTAGCTCAAGCCTGGGTGGAGT





CGGC






CVL54
oCVL101
ACATTAATGGCATCAATCAGTTCTATT
21




TCTCAATT




oCVL137
TTAGGATAGTGTCACCTGACGGATAAA
22




TGG




oCVL138
CCATTTATCCGTCAGGTGACACTATCC
23




TAAACCTGCTATAGGCTATCCACTGC




oCVL139
TCATTTATGATAAACAAAATTCTCC
24



oCVL140
GGAGAATTTTGTTTATCATAAATGACG
25




TACGAGGCAGAAGCCTCCAGGTCTGAC





CCAGCC




oCVL106
AGATTAGAACATGATGATTGGGTACAT
26




TCT






CVL55
oCVL141
GCAAGATCAGAGTGAGGAAGG
27



oCVL142
AATTGGTTGCGATAGGATTCTCTCTG
28



oCVL143
CCCCATCGATTTTAAGAGGGGCAGG
29



oCVL144
GGCATCATTGAATGATTCTGGCACAAC
30



oCVL145
TTCTTGACTCAATCTGAAGATGTAA
31



oCVL146
GCTGTAGGATCACAGCAGCA
32





CVL58
oCVL17
CAAGATGCACCTTCTCTCCAGTG
33


and
oCVL159
CGTACGTTAGCGCGCGATTTGAGCTTT
34


59

CCGAGACG




oCVL160
TCTCGGAAAGCTCAAATCGCGCGCTAA
35




CGTACGCACCTGCTATAGGCTATCCAC





TGCATC




oCVL161
AAACTGCAAGGGGTGATGTC
36





CVL65
oCVL119
CGGTGCCAACAACACAATCCACAATCT
37




ACA




oCVL262
GGCTGGGTCAGACCTGGAGGCTTCTGC
38




CTCGTACGAATTCATTTATGATAAACA





AAATTC






CVL86
oCVL422
AACACAATCCACAATCTACAGTC
39



oCVL423
GGTCAGGCCGTTGAAGTTGAAGTTCA
40





CVL108
oCVL422
AACACAATCCACAATCTACAGTC
41



oCVL611
GATGGCGTGGAACCAGGTCACGTTG
42



oCVL612
CAACGTGACCTGGTTCCACGCCATCAG
43




CGGCACCAATGGCACAAAGCG




oCVL613
CGGCCTGGTAGATTTCTGTAGAGATGT
44




CCCTCTCGAAGGGCTTCAGATTGCTCT





TTCTAAACAGCCGGTATCTATAATTGT





AGTTGCCGC




oCVL614
TACAGAAATCTACCAGGCCGGCAATAA
45




GCCTTGCAATGGCGTGGCCGGCGTGAA





CTGTTATTTCCCACTCCAGTCCTACGG





CTTCCGCCC




oCVL122
ATATGATGTGAGTAGGAAGTATGGCAG
46




GAG






CVL111
oCVL422
AACACAATCCACAATCTACAGTC
47



oCVL618
TCCCTTCCTGGACGTGTACTATCAC
48



oCVL619
CATATGTGGGGCGGAAGCCGTAGGA
49



oCVL620
GTGATAGTACACGTCCAGGAAGGGA
50



oCVL621
CAGTCCTACGGCTTCCGCCCCAC
51



oCVL122
ATATGATGTGAGTAGGAAGTATGGCAG
52




GAG






CVL113
oCVL5
ACAGTGGATTCCATAAGGTTCCTGC
53



oCVL6
GGAGAAGCTCAGATCAGTGGGATC
54



oCVL622
AGCTCATTCCAGCTCCGTCAGGTT
55



oCVL624
AACCTGACGGAGCTGGAATGAGCTAG
56




CCCTGCTATAGGCTATCCACTGCATCA




oCVL625
CGATAGGCAGGTCCACCAG
57



oCVL626
GGTCAGACCTGGAGGCTTCTGCCTCGT
58




ACGTCATCATTTATGATAAACAAAATT





CTCC




oCVL119
CGGTGCCAACAACACAATCCACAATCT
59




ACA




oCVL166
ACCAGGGGGAAAACGAAGTGG
60





Note:


The inserts for CVL48, 49, 60, 64, 67 and 80 are digested from plasmids, not PCR.






Five candidate vaccines based on the PIV5 CPI vector were evaluated in this study (Table 2). CVXGA1, 2, 3, and 5 have a SARS-CoV-S gene inserted between the PIV5 small hydrophobic (SH) and hemagglutinin (HN) genes. CVXGA2 has an additional insert, the SARS-CoV-2 nucleoprotein (N), inserted between the PIV5 HN and polymerase (L) genes (FIG. 1).









TABLE 2







Vaccine strains used in the hamster study













Vaccine dose



Virus
Insert & SARS-CoV-2 strain
(PFU/hamster







WT PIV5
None
9.7 × 104



CVXGA1
S from Wuhan strain
9.8 × 104



CVXGA2
S and N from Wuhan strain
8.7 × 104



CVXGA3
S from Beta variant
8.8 × 104



CVXGA5
S from Gamma variant
4.8 × 102










Study Outline.


Forty male, 5-7 week-old Syrian hamsters were used in this study (N=8 per vaccine group). The hamsters were intranasally immunized with 100 μL of WT PIV5 CPI virus, CVXGA1, CVXGA2, and CVXGA3 of approximately 1×105 plaque-forming units (PFU). For CVXGA5, hamsters received 100 uL of approximately 5×102 PFU (Table 2). At 36 days post-immunization (dpi), four hamsters from each group were challenged with 103 PFU of SARS-CoV-2 Wuhan strain (WA1), and the remaining four hamsters from each group were challenged with 103 PFU SARS-CoV-2 alpha variant (CA; BEI NR54011). Following challenge infection, the hamster weights were monitored for 5 days, the hamster lungs were harvested, and SARS-CoV-2 viral burden was quantified via plaque assay and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR).


Determination of infectious SARS-CoV-2 viral burden in hamster lungs post-challenge. Hamster lung homogenates were serially diluted in Dulbecco's modified Eagle medium (DMEM)+2% fetal bovine serum (FBS)+1% antibiotic/antimycotic and added to 12-well plates of Vero E6 cells. At 1 hour post-infection, the inoculum was removed, and a methylcellulose overlay (500 mL Opti-MEM+0.8% methylcellulose+2% FBS+1% antibiotic/antimycotic) was added to the wells. The plates were incubated for 3 days, the overlay was removed, and the cells were fixed with 40% acetone/60% methanol. The cells were stained with crystal violet, the number of plaques were counted and viral titers are expressed as log 10 PFU/mL.


Quantification of SARS-CoV-2 RNA load in hamster lungs post-challenge by qRT-PCR. For the standard curves, SARS CoV-2 challenge virus at concentrations of 2×107 PFU/mL and 4×108 PFU/mL for WA1 and CA1 respectively, was inactivated by 1:10 diluted Trizol reagent (ThermoFisher Scientific) with the genetic material preserved. Hamster lung homogenate was also treated with 1:10 diluted Trizol. Using a Qiagen Viral RNA extraction kit, RNA was extracted from 140 μL inactivated virus and lung homogenate and eluted in 15 buffer. WA1 and CA1 RNA was serial-diluted 1:10 in sterile water to serve as the standard curves. For the qRT-PCR reactions, 5 μL eluted RNA was mixed with 5 μL Thermofisher TaqPath 1-Step qPCR Master Mix (cat #A15300), 1.5 μL 2019-nCoV CDC EUA Authorized qPCR Probe Assay primer/probe mix, IDT (cat #10006770), and 8.5 μL water. qRT-PCR thermocycler settings were used as described on “CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel . . . Instructions for Use” page 26. To generate the standard curves, the viral titer was plotted on the x-axis and the cycle threshold (CT) value was plotted on the y-axis.


Results.


Hamster weight changes post-challenge infection. Following challenge with either WA1 or CA1/alpha SARS-CoV-2 variants, the hamster weights were monitored daily. For hamsters challenged with the WA1 variant, those immunized with CVXGA1, CVXGA2, CVXGA3, or CVXGA5 had minimal weight loss and resumed weight gaining within 5 dpc. However, the hamsters immunized with WT PIV5 CPI strain had weight loss and did not regain weight by the end of the study at 5 dpc (FIG. 3A). For the hamsters challenged with CA1/alpha, hamsters immunized with CVXGA1, CVXGA2, CVXGA3, or CVXGA5 had transient weight loss and resumed gaining weight by 3 dpc and had all surpassed their starting weight by 5 dpc. In contrast, the hamsters immunized with WT PIV5 maintained their starting weight (FIG. 3B).


CVXGA2 encoding both the S and N protein from SARS-CoV-2 Wuhan strain had the best weight gain after the viral challenge, indicating additonal protection offered by the inserted N gene in the vaccine candidate. In addition, the vaccine dose of CVXGA5 was approx. 100-fold lower than the other vaccine viruses, yet it offered protection as good as CVXGA1 and CVXGA3.


SARS-CoV-2 challenge virus titer in the lung. At 5 dpc, SARS-CoV-2 viral burden in the hamster lungs was quantified. Hamsters immunized with WT PIV5 CPI had an average titer of 2.5×104 and 6.2×104 PFU/mL following challenge with WA1 and CA1/alpha, respectively. In contrast, none of the CVXGA-immunized hamsters had detectable infectious virus in their lungs (FIGS. 4A-4B). This data demonstrated that the CPI-vectored SARS-CoV-2 vaccine candidates, including CVXGA5 with 100-fold lower dose, offered complete protection in the lower respiratory tract of hamster against homologous and heterologous virus challenge infections.


Quantitation of SARS-CoV-2 RNA in the vaccinated hamster lungs following challenge infection. SARS-CoV2 challenge virus RNA load in the hamster lungs were quantitated by qRT-PCR. Note that a lower cycle threshold (CT) value corresponds to a higher viral titer. Hamsters immunized with WT PIV5 CPI and challenged with WA1, had CT values between 14.7 and 18.2, which equates to 8.9×103 and 6.5×102 PFU/rxn (FIGS. 5A-5B). Hamsters immunized with WT PIV5 CPI and challenged with CA1/alpha strain, had CT values between 12.7 and 14.5, which equates to 3.8×104 and 8.3×103 PFU/rxn (FIGS. 5B-5D). For both challenge SARS-CoV2 variants, hamsters immunized with CVXGA1 or CVXGA2 had CT values indicative of less than one infectious viral particle per rxn (FIGS. 5A-5D). Three of four hamsters immunized with CVXGA3 and challenged with WA1 were PCR-negative, and the fourth hamster had a CT value corresponding to less than one infectious virus particle per reaction (FIGS. 5A-5B). For the hamsters immunized with CVXGA3 and challenged with CA1/alpha, one hamster was PCR-negative and two hamsters had CT values indicative of less than one infectious particle per reaction. The remaining hamster had CT value 19.78, which corresponds to approximately 100 PFU/rxn (FIGS. 5B-5D). For the CVXGA5-immunized hamsters, one WA1-challenged hamster was PCR-negative, while one WA1-challenged and three CA1/alpha-challenged hamsters had CT values indicative of less than one infectious particle per mL. For the remaining CVXGA5-immunized hamsters, two challenged with WA1 had CT values correlating to less than 10 PFU/rxn and one challenged with CA1/alpha had a CT value corresponding to approximately 1.5 PFU/rxn (FIGS. 5A-5D). Compared to the PIV5 CPI immunized animals, CVXGA1, 2, 3 and 5 immunized hamsters had greatly reduced challenge virus burden not only to the homologous WA1 strain but also to the heterologous CA/alpha strain, which were either undetectable or at very low levels.


In order to protect against SARS-CoV-2 variants, recombinant PIV5 CPI-vectored candidate vaccines expressing the S protein alone or with S and N from SARS-CoV-2 Wuhan strain, beta, and gamma variants have been developed. All four CVXGA candidate vaccines offered significant protection from weight loss not only from homologous but also heterologous SARS-CoV-2 challenge virus infection. Furthermore, no infectious SARS-CoV-2 live virus was detected in the lungs of CVXGA-immunized hamster 5 dpc, which was confirmed by the low/no viral RNA burden by qRT-PCR assay. These results indicate that PIV5 CPI vectored CVXGA candidate SARS-CoV-2 vaccines are effective in providing protection against SARS-CoV-2 variants.


Example 2: Protective Efficacy of CVXGA1 and CVXGA3 in AGM

Materials and methods.


Two candidate SARS-CoV-2 vaccine viruses based on the PIV5 CPI vector were evaluated in this study. CVXGA 1 and 3 have the SARS-CoV-S gene from variants Wuhan (WA1) and California/alpha (CA1/alpha), respectively, inserted between the PIV5 small hydrophobic (SH) and hemagglutinin (HN) genes. BLB-201 has the fusion (F) gene from respiratory syncytial virus (RSV) in the same location as the control (FIG. 1).


Study Outline.


Twelve AGMs were used in this study with 4 per vaccine group. The AGMs were intranasally immunized with 106 PFU/AGM of vaccine virus. Serum was collected prior to dosing (Day −1) and 28 days post-immunization (dpi) to quantify the anti-S IgG antibody titer via enzyme-linked immunosorbent assay (ELISA). Blood was collected at −1, 7, 14, and 28 dpi to quantify the CoV-S-specific cellular response. At 40 dpi, the mice were challenged with 1.5×106 PFU SARS-CoV-2 CA1/alpha variant. At 2, 4, and 7 days post-challenge (dpc), AGM nasal washes (NW) and bronchoalveolar lavage (BAL) were collected, and SARS-CoV-2 viral burden was quantified via plaque assay and qRT-PCR (FIG. 6 and Table 3).









TABLE 3







Efficacy of CVXGA1 and CVXGA3 in African green monkeys











Group
Animal





(N = 4)
ID
Virus
Gene insert
Lot# and titer














Group 4
9867
CVXGA1
CPI-S
5/1/17 SP



9845

(Wuhan)
1.5 × 107 pfu/ml



58169






9829





Group 6
9669
BLB-201
CPI-RSV-F
210322MCBCHD



9839


2 × 107 pfu/ml



9854






9861





Group 7
9866
CVXGA3
CPI-S-
210427ZL



9851

B.1.135.1
2.1 × 107 pfu/ml



9814






9828









ELISA to quantify anti-SARS-Cov-2-S IgG antibodies. For the enzyme-linked immunosorbent assay (ELISA), Immulon 2HB 96-well microtiter plates were coated with 100 μL/well purified SARS-CoV-2 S protein at 1 μg/mL. Serum samples were diluted 3-fold in KPL Wash Solution (SeraCare Life Sciences, Inc., Milford, Mass.) supplemented with 0.5% bovine serum albumin (BSA) and 5% nonfat milk. Serum samples were incubated at 100 μL/well for 1 h. After washing with KPL Wash Solution three times, the plates were incubated for 1 h with a 1:1000 dilution of horseradish peroxidase-labelled goat anti-monkey IgG antibody (Southern Biotech, Birmingham, Ala.) in KPL Wash Solution supplemented with 0.5% BSA and 5% nonfat milk. After the plates were washed three times, antibody-antigen binding was realized using KPL SureBlue Reserve TMB Microwell Peroxidase Substrate (SeraCare Life Sciences, Inc.) and a Glomax 96 microplate luminometer (Promega) set at OD450. An antibody titer was calculated as the highest serum dilution at which the OD450 was greater than two standard deviations above the mean OD450 of naïve serum.


ELISPOT to quantify SARS-CoV-2-S-specific cellular response. SARS-CoV-2-specific peripheral blood mononuclear cells (PBMCs) in blood were quantified by ELISpot assay at days −1, 7, 14, and 28 dpi. The number of spots was reported as the number of IFN-γ spots per 2×105 PBMCs.


Plaque assays to determine infectious SARS-CoV-2 viral burden in AGM NW and BAL post-challenge. NW and BAL were serially diluted in Dulbecco's modified Eagle medium (DMEM)+2% fetal bovine serum (FBS)+1% antibiotic/antimycotic and added to 12-well plates of Vero E6 cells. At 1 hour post-infection, the inoculum was removed, and a methylcellulose overlay (500 mL Opti-MEM+0.8% methylcellulose+2% FBS+1% antibiotic/antimycotic) was added to the wells. The plates were incubated for 3 days, the overlay was removed, and the cells were fixed with 40% acetone/60% methanol. The cells were stained with crystal violet, the number of plaques were counted, and viral titers are expressed as log 10 PFU/mL.


Quantification of SARS-CoV-2 RNA in AGM NW and BAL by qRT-PCR. AGM NW and BAL samples were inactivated by 1:10 diluted Trizol reagent (ThermoFisher Scientific) with the genetic material preserved. Using a Qiagen Viral RNA extraction kit, RNA was extracted from 140 μL inactivated sample and eluted in 15 μL buffer. For the qRT-PCR reactions, 5 μL eluted RNA was mixed with 5 μL Thermofisher TaqPath 1-Step qPCR Master Mix (cat #A15300), 1.5 μL 2019-nCoV CDC EUA Authorized qPCR Probe Assay primer/probe mix, IDT (cat #10006770), and 8.5 μL water. qRT-PCR thermocycler settings were used as described on “CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel . . . Instructions for Use” page 26.


Results.


SARS-CoV-2-S-specific cellular response. Following immunization, blood was collected at days −1, 7, 14, and 28 to quantify the SARS-CoV-2-S-specific cellular response. For all groups, PBMCs collected at day −1 failed to respond to SARS-CoV-2-S stimulation. Following immunization, AGMs immunized with CVXGA1 and CVXGA3 generated a cellular response that is SARS-CoV-2 S protein-specific. No SARS-CoV-2-specific cellular response was detected in the BLB control animals (group 6), the cellular responses from animals immunized with CVXGA1 and CVXGA3 increased at each time point post-immunization, Days 7, 14 and 28 (FIGS. 7A-7B). CVXGA3 seems to induce a slightly higher cellular response than CVXGA1.


SARS-CoV-2-S IgG antibody response. At −1 and 28 dpi, anti-SARS-CoV-2-S IgG antibodies were quantified. Interestingly, two CVXGA3- and three CVXGA1-immunized AGMs had detectable anti-S antibodies prior to immunization. For all except one CVXGA1-immunized AGM, the anti-S antibody titers increased from −1 to 28 dpi to over 103. For all CVXGA3-immunized AGMs, the anti-S antibody titers increased from −1 to 28 dpi to over 104. One AGM, who had detectable antibodies prior to immunization with CVXGA1, did not have an increase in its anti-S IgG antibody titer (FIG. 8).


Infectious SARS-CoV-2 challenge virus titer in NW and BAL of vaccinated AGM. At 2, 4, and 7 dpc, NW and BAL were collected and infectious SARS-CoV-2 viral burden was quantified. In the NW, only one AGM, immunized with vector control, had detectable infectious virus (FIG. 9A). However, all four vector control-immunized AGMs had detectable infectious challenge virus in the BAL at 2 dpc with the highest titer being 103 PFU/mL. At 4 and 7 dpc, one of two and two of two vector control-immunized AGMs had detectable virus in their BAL. Three of four CVXGA1-immunized AGMs had detectable infectious virus in their BAL at 2 dpc but not at later time points. In contrast, none of the CVXGA3-immunized AGMs had detectable infectious virus in their BAL at any time point (FIG. 9B).


Quantitation of SARS-CoV-2 RNA in the vaccinated AGM NW and BAL following challenge infection. At 2, 4, and 7 dpc, NW and BAL were collected to quantitate SARS-CoV2 challenge virus RNA load by qRT-PCR. Note that a lower cycle threshold (CT) value corresponds to a higher viral titer. AGMs immunized with vector control had CT values corresponding to infectious virus in their BAL at all time points. For CVXGA1-immunized AGMs, three of four at 2 dpc and one of two at 3 dpc had CT values corresponding to infectious virus in their BAL. For CVXGA3, two immunized AGMs had CT values corresponding to infectious virus in their BAL at 2 dpc (FIG. 10A). For the NW, all vector control-immunized AGMs had CT values corresponding to infectious virus at 2 dpc. At 4 and 7 dpc, only half of the vector control-immunized AGMs had CT values corresponding to infectious virus in their NW. Two CVXGA1-immunized AGMs had CT values corresponding to infectious virus at 2 dpc. In contrast, no CVXGA3-immunized AGMs had CT values corresponding to infectious virus in their NW at any time point (FIG. 10B). Compared to the vector control-immunized animals, CVXGA1- and 3-immunized AGMs had greatly reduced challenge virus burden.


Both CVXGA1 and CVXGA3 candidate vaccines induced anti-SARS-CoV-2 S IgG antibodies and SARS-CoV-2 S-specific cellular responses. Furthermore, no infectious SARS-CoV-2 live virus was detected in the NW of CVXGA-immunized AGMs 2, 4, or 7 dpc. For CVXGA3-immunized AGMs, no infectious virus was detected in the BAL. These results were confirmed by the low/no viral RNA burden by qRT-PCR assay, indicating that PIV5 CPI vectored CVXGA candidate SARS-CoV-2 vaccines are effective in providing protection against SARS-CoV-2 alpha variant. CVXGA3 appears to provide a better protection against SARS-CoV-2 alpha variant challenge infection.


Example 3: Construction and Characterization of PIV5-Vectored SARS-CoV-2 Vaccines

Materials and Methods.


Cells: Vero E6 cells were maintained in Dulbecco's modified Eagle media (DMEM) supplemented with 5% fetal bovine serum (FBS) plus 100 IU/mL penicillin and 100 ug/mL streptomycin (1% P/S; Mediatech Inc, Manassas, Va., USA). Serum-free (SF) Vero cells were maintained in VP-SFM (ThermoFisher Scientific) plus 4 mM GlutaMax (Gibco). Vero-TEMPRSS cells were obtained from Dr. Jeff Hogan, University of Georgia, and maintained in DMEM+10% FBS+1 mg/mL G418. All cells were incubated at 37° C., 5% CO2.


Plasmids and virus rescue: The construction of a plasmid encoding for PIV5 antigenome and generation of recombinant PIV5 has already been described (He, B., et al., Virology, 237(2):249-60 (1997)). To construct plasmids encoding for the antigenome of CVXGA1, CVXGA3, CVXGA5, CVXGA13, and CVXGA14, the Spike (S) genes from SARS-CoV-2 WA1, alpha, gamma, delta, and omicron, respectively, were placed into an additional open reading frame (ORF) between the PIV5 SH and HN genes. The S cytoplasmic tail was replaced by the PIV5 fusion (F) protein cytoplasmic tail. To construct CVXGA2, the SARS-CoV-2 WA1 nucleoprotein (N) gene was placed into an additional ORF between the PIV5 HN and L genes of CVXGA1. Primer sequences are available upon request. To generate recombinant PIV5 viruses CVXGA1, CVXGA2, CVXGA3, CVXGA5, CVXGA13, and CVXGA14, the Neon Transfection System (Invitrogen) was used to electroporate SF Vero cells with 1.9 μg pPIV5-NP, 0.6 μg pPIV5-P, 3.1 μg pPIV5-L, 3.1 μg pT7-polymerase, and 6.3 μg antigenome. Recovered virus was amplified in SF Vero cells, single viral isolates were obtained by limiting dilution or plaque purification, and the viral genomes were verified by RT-PCR and Sanger sequencing.


Virus propagation: The recombinant PIV5 viruses were propagated in SF Vero cells. The cells were infected at a multiplicity of infection (MOI) 0.001 PFU in VP-SFM+4 mM GlutaMax. One hour post-infection, the media was replaced with fresh VP-SFM 4 mM GlutaMax. After 5 to 7 days of incubation at 37° C. with 5% CO2, the media was collected and centrifuged at 1500 rpm for 10 mins to pellet cell debris. The supernatant was mixed with 0.1 volume of 10× sucrose-phosphate-glutamate (SPG) buffer or 10×SPG+10% Arginine, aliquotted, flash-frozen in liquid nitrogen, and stored at −80° C. The PIV5 virus stocks were titrated via immunostain in Vero cells.


The SARS-CoV-2 viruses were propagated in Vero cells with DMEM+1% FBS+1× P/S. WA1 (BEI NR-52281) and alpha variant (BEI NR-54011) were obtained from BEI Resources. The delta variant was provided by Dr. Michael Gale, University of Washington. The omicron variant was provided by Dr. Jeff Hogan, University of Georgia.


Immunofluorescence assay (IFA): To detect PIV5 V/P, SARS-CoV-2 S, and SARS-CoV-2 N, immunofluorescence assays were performed. Vero cells were infected at MOI 0.01 with PIV5, CVXGA1, CVXGA2, CVXGA3, CVXGA5, CVXGA13, or CVXGA14. 3 days post-infection, the cells were fixed with 80% methanol. The cells were incubated with mouse anti-PIV5 V/P, rabbit anti-SARS-CoV-2 S (Sino Biological catalog no. 40150-R007), or SARS-CoV-2 N (ProSci catalog no. 35-579) antibodies at 1:500 in PBS+3% BSA for 1 hr. Next, the cells were washed with PBS and incubated with goat a-mouse Cy3 (KPL) or goat a-rabbit Cy3 (KPL) at 1:500 in PBS+3% BSA for 30 mins. The cells were washed with PBS and imaged with an EVOS M5000 microscope (Thermo Fisher Scientific).


Results


A PIV5-vectored vaccine for SARS-CoV-2 was previously generated by inserting the SARS-CoV-2 WA1 S gene between the PIV5 SH and HN genes (CVXGA1). Additionally, the cytoplasmic tail of the S protein was replaced with the cytoplasmic tail from the PIV5 F protein. A single, intranasal dose of CVXGA1 was shown to protect K18-hACE2 mice from lethal infection with the WA1 strain, the initial circulating strain in the US, and blocks contact transmission in ferrets (An, D., et al., Sci Adv, 7(27) (2021)). To determine whether expressing the N protein of SARS-CoV2 as an additional antigen enhances protection afforded by the S antigen alone, PIV5 expressing both S and N (CVXGA2) was generated. During the study period, SARS-CoV 2 variants of concern (VOC) emerged and some of them became dominant strains circulating in different regions at different times. Thus, PIV5-vectored vaccine candidates expressing S from SARS-CoV-2 VOC were generated in a similar manner as CVXGA1 (FIG. 11): variants alpha (CVXGA3), gamma (CVXGA5), delta (CVXGA13), and omicron (CVXGA14) (collectively called CVXGA vaccines). All variant S genes had the cytoplasmic tail replaced with the PIV5 F cytoplasmic tail.


The vaccine viruses were recovered by electroporating the plasmid containing the PIV5 genome with the SARS-CoV-2 antigen along with plasmids encoding for PIV5 NP, P, and L proteins as well as T7 polymerase. The recovered viral genomes were confirmed with RT-PCR and sequencing. To confirm antigen expression, Vero cells were infected at MOI 0.01 with PIV5, CVXGA1, CVXGA2, CVXGA3, CVXGA5, CVXGA13, or CVXGA14 and assayed for immunofluorescence with WA1 S-specific antibody. As expected, S expression was detected in cells infected with CVXGA1, 2, 3, 5, 13 and 14. Additionally, SARS-CoV-2 N expression was only detected in cells infected with CVXGA2 (FIGS. 12A-12S). Compared to PIV5 vector-infected cells, all the PIV5-vectored vaccines had increased syncytia, indicating that SARS-CoV-2-S is functional (FIGS. 12T-12AA).


Example 4: PIV5-Vectored SARS-CoV-2 Vaccines Induce an Anti-S Humoral Response in Hamsters

Materials and Methods.


Hamsters: Five-to-seven-week-old Golden Syrian hamsters were obtained from Charles River Laboratories. The hamsters were single-housed in biosafety level 2 facilities with ad libitum access to food and water. Pre-challenge procedures were performed at the University of Georgia Biological Sciences Animal Facility. The hamsters were transferred to the University of Georgia Animal Health Research Center for the challenge and post-challenge procedures. The hamsters were anesthetized for immunization, blood collection, and challenge by intraperitoneal injection of 100 μL ketamine/acepromazine cocktail. All experiments were performed in accordance with protocols approved by the Institutional Animal Care and Use Committee at the University of Georgia.


Immunization and challenge of hamsters: The hamsters were anesthetized by intraperitoneal injection of 100 μL ketamine/acepromazine cocktail. To administer intranasal immunizations, anesthetized hamsters were placed on their backs, a pipette was used to dispense 100 μL inoculum onto their noses (50 μL each nostril), and the inoculum was allowed to drain into their respiratory tracts. They were recovered on heating pads.


A Covid-19 mRNA vaccine was obtained from a clinical site after it was thawed and stored at −80° C. 2 μg mRNA vaccine in 50 μL was administered via intramuscular injection.


For study AE19, hamsters (n=8) received a single intranasal immunization of 100 μL of 105 plaque-forming units (PFU) PIV5, CVXGA1, CVXGA2, CVXGA3, or CVXGA5. At 28 dpi, blood was collected from the hamster saphenous vein for serological analysis. At 36 days post immunization (dpi), the hamsters were anesthetized, four hamsters were challenged with 103 PFU of SARS-CoV-2 Wuhan strain (WA1), and the remaining four hamsters were challenged with 103 PFU SARS-CoV-2 alpha variant (CA; BEI NR54011). Challenge virus was delivered intranasally with a Teleflex MAD device. Following challenge infection, the hamster weights were monitored for 5 days, the hamster lungs were harvested and homogenized in approximately 1.7 mL sterile PBS, and SARS-CoV-2 viral burden was quantified via plaque assay and real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR).


For study AE23, hamsters received intramuscular immunizations of 100 μL PBS (n=20, group 1) or 2 μg mRNA COVID vaccine (n=20, group 2). At 21 dpi, hamsters that received the mRNA vaccine were boosted with the mRNA vaccine again. At 28 dpi, blood was collected for serological analysis. At 35 dpi following initial immunization, hamsters that received PBS during the first immunization received either 100 μL PBS i.n. (n=5, group 1A), 100 μL 3×105 PFU CVXGA1 (n=5, group 1B), 100 μL 2×105 PFU CVXGA3 (n=5, group 1C), or 100 μL 1.5×105 PFU CVXGA13 (n=5, group 1D). Group 2 hamsters that received two doses of mRNA received 100 μL PBS (n=4, group 2A), 100 μL 3×105 PFU CVXGA1 (n=4, group 2B), 100 μL 2×105 PFU CVXGA3 (n=4, group 2C), 100 μL 1.5×105 PFU CVXGA13 (n=4, group 2D), or a third dose of mRNA (n=4, group 2E). Hamsters were anesthetized for intranasal immunizations but not intramuscular injections. Blood was collected at 54 dpi. At 63 dpi, the hamsters were challenged with 104 PFU SARS-CoV-2 delta variant. Following challenge infection, hamster weights were monitored for 5 days, the hamster lungs were harvested, and SARS-CoV-2 viral burden was quantified via plaque assay and RT-qPCR.


For study AE24, hamsters received 100 μL PBS i.n. (n=5, Group 1), 2 μg mRNA COVID vaccine (n=25, Group 2), or 100 μL 7×104 PFU CVXGA1 (n=10, Groups 3 & 4). At 29 dpi, hamsters that received the mRNA vaccine were boosted with the mRNA vaccine again and group 3 hamsters received another dose of CVXGA1. At 91 dpi following initial immunization, hamsters who received two doses of mRNA received 2 μg mRNA vaccine (n=5, Group 2A), 100 μL 7×104 PFU CVXGA1 (n=5, Group 2B), 100 μL 103 PFU CVXGA13 (n=5, Group 2C), 100 μL PBS i.n. (n=5, Group 2D), or 100 μL 104 PFU CVXGA14 (n=5, Group 2E). Hamsters were anesthetized for intranasal immunizations but not intramuscular injections. Blood was collected at 36 and 108 dpi. At 116 dpi, the hamsters were challenged with 104 PFU SARS-CoV-2 delta variant. Following challenge infection, hamster weights were monitored for 5 days, the hamster lungs were harvested, and SARS-CoV-2 viral burden was quantified via plaque assay and RT-qPCR.


All animal experiments were performed according to the protocols approved by the Institutional Animal Care and Use Committee at the University of Georgia.


Enzyme-linked immunosorbent assay (ELISA): To quantify the anti-SARS-CoV-2 S and RBD humoral response, hamster serum was analyzed via ELISA. Immulon® 2HB 96-well microtiter plates were coated with 100 μL SARS-CoV-2 S or RBD at 1 μg/mL. For all ELISAs, plates were coated with SARS-CoV-2 S and RBD from the WA1 strain. S and RBD were purified as described previously. (An, D., et al., Sci Adv, 7(27) (2021)). Hamster serum was serial diluted two-fold and incubated on the plates for 2 hrs. Horseradish peroxidase-labelled goat anti-mouse IgG secondary antibody (Southern Biotech, Birmingham, Ala.) was diluted 1:2000 and incubated on the wells for 1 hr. The plates were developed with KPL SureBlue Reserve TMB Microwell Peroxidase Substrate (SeraCare Life Sciences, Inc., Milford, Mass.), and OD450 values were detected with a BioTek Epoch Microplate Spectrophotometer (BioTek, Winooski, Vt.). Antibody titers were calculated as log 10 of the highest serum dilution at which the OD450 was greater than two standard deviations above the mean OD450 of naïve serum.


Results.


Golden Syrian hamsters are susceptible to SARS-CoV 2 infection. (Chan, J. F., et al., Clin Infect Dis, 71(9):2428-2446 (2020)) To test efficacy of new PIV5-vectored COVID-19 vaccines in hamsters, their ability to induce an immune response in hamsters was examined. Golden Syrian hamsters were immunized with a single, intranasal dose of 105 plaque-forming units (PFU) PIV5 vector, CVXGA1, CVXGA2, CVXGA3, or 5×102 PFU CVXGA5 (FIG. 13A). 28 days post-immunization (dpi), blood was collected from the hamsters and serum anti-SARS-CoV-2-S IgG antibodies were quantified by ELISA. While hamsters immunized with PIV5 vector had no detectable anti-SARS-CoV-2-S antibodies, a single intranasal dose of CVXGA1, CVXGA2, and CVXGA3 induced mean antibody titers of over 10,000, the upper limit of detection for the assay. Even CVXGA5, at a lower immunization dose, was able to induce an anti-S ELISA titer over 9,870 (FIG. 13B).


Example 5: CVXGA Vaccines Protect Against Homologous and Heterologous Challenges

Materials and methods.


Neutralization assays: To quantify the SARS-CoV-2-neutralizing antibodies generated by the hamsters, microneutralization assays were performed. Hamster serum was heat-inactivated at 56° C. for 45 mins and serially diluted two-fold. The serum was mixed 1:1 with 6×103 focus-forming units (FFU)/mL SARS-CoV-2 WA1, delta, or omicron. The serum/virus mixture was incubated at 37° C. for 1 hr before being incubated on 96-wells of Vero cells for WA1 or Vero TEMPRSS2 cells for delta and omicron. One hour post-infection, a methylcellulose overlay (Dulbecco's modified Eagle medium (DMEM)+5% fetal bovine serum (FBS)+1% penicillin/streptomycin+1% methylcellulose) was added on top of the serum/virus mixture. The plates were incubated at 37° C., 5% CO2 for 24 hrs. The methylcellulose overlay was removed, the wells were washed with PBS, and the cells were fixed with 60% methanol/40% acetone. The number of infected cells were quantified via immunostain. Neutralization titers were calculated as log 10 of the highest serum dilution at which the virus infectivity was reduced by at least 50%.


Plaque assay for infectious virus: Following euthanasia, whole hamster lungs were removed, added to approximately 1.7 mL sterile PBS, and homogenized. To quantify infectious SARS-CoV-2, plaque assays were performed with lungs from AE19 and AE23, and FFU assays were performed with lungs from AE24.


For the plaque assays, lung homogenates were serially diluted in Dulbecco's modified Eagle medium (DMEM)+2% fetal bovine serum (FBS)+1% antibiotic/antimycotic and added to 12-well plates of Vero E6 cells for SARS-CoV-2 WA1 and alpha variant or Vero TEMPRSS2 cells for delta and omicron variants. At 1 hour post-infection, the inoculum was removed, and a methylcellulose overlay (500 mL Opti-MEM+0.8% methylcellulose+2% FBS+1% antibiotic/antimycotic) was added to the wells. The plates were incubated for 3 days, the overlay was removed, and the cells were fixed with 60% methanol/40% acetone. The cells were stained with crystal violet, the number of plaques were counted, and viral titers are expressed as PFU/mL of lung homogenate.


qPCR: SARS-CoV-2 viral RNA levels were quantified by RT-qPCR. SARS-CoV-2 virus was inactivated by mixing 100 μL lung homogenate with 900 μL TRIzol (Invitrogen). Using a QIAgen RNA extraction kit, RNA was extracted from 140 μL homogenate/TRIzol and eluted in 15 μL of elution buffer, of which 5 μL was used in the qRT-PCR reaction. qRT-PCR was performed according to the protocol described in the “CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel . . . Instructions for Use” (page 26) with Applied Biosystems TaqPath One Step RT qPCR Master Mix and SARS-CoV-2 Research Use Only qPCR Primer and Probe Kit primer/probe mix N1. SARS-CoV-2 viral RNA was extracted from SARS-CoV-2 WA1, alpha variant, and delta variant viruses of known titers. RNA was extracted from 140 μL virus and eluted in 15 μL of elution buffer. The viral RNA was serially diluted 10-fold and 5 μL from each dilution was used in the RT-qPCR assay. To generate a standard curve, the viral titer was plotted on the x-axis and the CT value was plotted on the y-axis. The standard curve was used to calculate the CT value that corresponds to 1 PFU/rxn. The standard curve was also used to calculate PFU/rxn from the CT values of homogenized lung RNA samples. The CT value of RNA extracted from sterile elution buffer was designated the PCR negative cutoff


Results.


To assess the efficacy of PIV5-vectored SARS-CoV-2 vaccines against homologous and heterologous challenges, CVXGA-immunized hamsters were challenged with either 103 PFU SARS-CoV-2 WA1 (USA-WA01/2020) or alpha variant (CA; BEI NR54011) at 36 dpi (FIG. 13A). The hamster weights were monitored daily for 5 days post-challenge (dpc). Following challenge with WA1, hamsters immunized with PIV5 vector lost weight and did not recover before the study was terminated. In contrast, hamsters immunized with CVXGA1, CVXGA2, CVXGA3, or CVXGA5 lost weight at day 1 post-challenge but returned to pre-challenge weights by 3 or 4 dpc (FIG. 14A). While challenge with alpha variant induced less severe weight loss in PIV5 vector-immunized hamsters, hamsters immunized with CVXGA1, CVXGA2, CVXGA3, or CVXGA5 had significantly higher body weights compared to PIV5 vector-immunized hamsters at 5 dpc. In both virus challenge groups, hamsters immunized with CVXGA2 had the highest mean body weight gains following challenge (FIG. 14B), suggesting that N as an additional antigen provided protection.


To quantify viral burden in the lungs, hamster lungs were harvested and homogenized 5 dpc. Infectious virus was quantified by plaque assay. Hamsters immunized with PIV5 vector had infectious virus of over 4 log 10 PFU/mL lung homogenate following challenge with WA1 or alpha variant, while no infectious WA1 or alpha variant was detected in hamsters immunized with CVXGA1, CVXGA2, CVXGA3, or CVXGA5 (FIGS. 14C-14D; limit of detection, LOD, 25 PFU/mL). Viral RNA in the lung, were detected with RT-qPCR. Hamsters immunized with PIV5 vector and challenged with WA1 and alpha variant had mean cycle threshold (CT) values of 15.9 and 13.5, respectively (FIGS. 14E-14F). Following challenge with WA1 or alpha variant, hamsters that received a single intranasal dose of CVXGA1 or CVXGA2 had CT values indicative of less than 1 PFU per reaction (PFU/rxn). Interestingly, CVXGA3-immunized hamsters had CT values indicative of less than 1 PFU/rxn following challenge with WA1 but two hamsters had CT values equating to 1 and 96 PFU/rxn following challenge with alpha variant (FIGS. 14E-14F, FIGS. 18A-18C). A single dose of CVXGA2 performed the best against heterologous challenge with alpha variant (FIG. 14F), again, suggesting that SARS-CoV-2 N might be protective.


Example 6: CVXGA Vaccines Protect Against Delta Challenge

Results.


As of May 2022, delta variant is one of two VOCs circulating in the United States. Therefore, we assessed the efficacy of our primary vaccine candidate, CVXGA1, against heterologous challenge with delta variant and test a vaccine expressing S from delta variant against homologous challenge. Hamsters received a single, intranasal dose of PBS or 105 PFU CVXGA1, CVXGA3, or CVXGA13. 19 dpi, blood was collected and serum anti-SARS-CoV-2 WA1 S and -RBD IgG antibodies were quantified via ELISA. Immunization with CVXGA1, CVXGA3, and CVXGA13 elicited anti-S antibodies with mean titers of over 10,000 (FIG. 15B). Interestingly, hamsters immunized with CVXGA13 had the highest quantity of anti-WA1 RBD antibodies with a mean titer of 51,200 (FIG. 14C).


At 28 dpi, the hamsters were intranasally challenged with 104 PFU SARS-CoV-2 delta variant and their weights were monitored for 5 days. Beginning at 2 dpc, hamsters immunized with PBS experienced weight loss that steadily declined until the study was terminated. In contrast, hamsters immunized with CVXGA1, CVXGA3, or CVXGA13 experienced weight gain after 2 days post-challenge. While not statistically significant, hamsters immunized with CVXGA13 had greater weight gain than hamsters immunized with CVXGA1 or CVXGA3, indicating that PIV5 expressing S from SARS-CoV-2 delta variant protected hamsters best from weight loss following homologous challenge with delta variant (FIG. 15D). To further assess the vaccine efficacy, lungs were harvested at 5 dpc and subjected to plaque assay and RT-qPCR. While hamsters immunized with CVXGA1, CVXGA3, or CVXGA13 did not have detectable infectious challenge virus in their lung homogenates, hamsters immunized with PBS had a mean titer of 3×104 PFU/mL lung homogenate (FIG. 15E). SARS-CoV-2 delta RNA was detected in lung homogenates via RT-qPCR. Four of five hamsters immunized with CVXGA1 and all hamsters immunized with CVXGA3 or CVXGA13 had CT values indicative of no infectious virus. One CVXGA1-immunized hamster had a CT value of 26.39 (FIG. 15F). The weight loss and lung viral burden data from this study indicate that single, intranasal doses of CVXGA1 and CVXGA3 protect hamsters from heterologous challenge and CVXGA13 protects hamsters from homologous challenge with delta variant.


Example 7: CVXGA Vaccines Boost the Antibody Response Induced by a mRNA COVID-19 Vaccine

Results.


As of May, 2022, 67 percent of individuals in the United States are fully vaccinated against COVID-19. However, data suggests that vaccine-induced immunity wanes over time and is less effective against SARS-CoV-2 variants (Planas, D., et al., Nature, 596(7871): 276 (2021); Zhang, L., et al., Emerg Microbes Infect, 11(1): 1 (2022); Feikin, D. R., et al., Lancet, 399(10328): 924 (2022)). To assess the efficacy of CVXGA1, we compared one (1×CVXGA1) and two (2×CVXGA1) intranasal doses of CVXGA1 to two intramuscular doses of a mRNA COVID-19 vaccine (2× mRNA) (FIG. 16A). Blood was collected 7 days following the second immunization and anti-SARS-CoV-2-S IgG antibodies were quantified via ELISA. Hamsters who received 2× mRNA had highest anti-S ELISA titer, 2×CVXGA1-immunized hamsters had higher anti-S titers than 1×CVXGA1-immunized hamsters, whose mean anti-WA1 S antibody titer was 51,200 (FIG. 16B). To assess the neutralizing ability of the antibodies, the hamster serum was used in microneutralization assays with SARS-CoV-2 WA1, delta variant, and omicron variant. While 2× mRNA generated a high level of anti-WA1 neutralizing antibody (4,640 at 7 days post-second dose), both 2× and 1×CVXGA1 generated comparable levels of anti-WA1 neutralization antibody even though they had lower levels of anti-S ELISA titers (FIGS. 16B-16E). Consistent with reduced cross-reactivity of mRNA-generated antibodies with delta and omicron VOC, delta- and omicron-neutralizing levels were lower than anti-WA1 in hamsters immunized with 2× mRNA at 1,413 and 363 respectively at 7 days post-second dose. As expected, 1× and 2×CVXGA1 generated anti-delta neutralization levels that were moderately lower than anti-WA1; however, 1× and 2×CVXGA1-generated anti-omicron neutralization levels were significantly lower (FIGS. 16C-16E).


To compare longevity of antibody responses in the hamsters, 79 days after boost (day 108 after initial immunization) sera were collected. Anti-S ELISA titers dropped over this time period by 56.5, 56.5, and 24.3 percent for 2× mRNA, 2×CVXGA1, and 1×CVXGA1, respectively (FIG. 16B). Reduction of neutralizing antibody titers in 2× mRNA-immunized hamsters was substantial with 20, 60, and 40 percent of hamsters having no detectable WA1-, delta-, and omicron-neutralizing antibodies 79 post-boost. In contrast, serum from all hamsters immunized with 2×CVXGA1 maintained levels of neutralizing antibodies against WA1, delta variant, and omicron variant (FIGS. 16C-16E).


87 days after the second immunization, the hamsters were challenged with delta variant and the hamster weights were monitored for five days. Compared to hamsters who were immunized with PBS, hamsters who received two doses of CVXGA1 had significant weight gain following challenge. In contrast, hamsters who received two doses of mRNA vaccine did not experience weight gain that was statistically significant (FIG. 16F). To quantify the viral burden in the hamster lungs post-challenge, lungs were collected and homogenized at 5 dpc. While PBS-immunized hamsters had mean lung titers of 5.2×103 FFU/mL lung homogenate, none of the vaccinated hamsters had detectable infectious virus in their lung homogenate (FIG. 16G). However, RT-qPCR revealed that all hamsters immunized with two doses of mRNA vaccine had SARS-CoV-2 vRNA levels indicative of infectious virus with the mean CT value equating to 38 PFU per RT-qPCR reaction (FIG. 16H).


Example 8: Boosting with CVXGA1 Improves Protection of Hamsters Immunized with mRNA COVID-19 Vaccine

Results.


Due to large populations having already immunized with COVID-19 vaccines, we investigated the use of CVXGA vaccines as a boost (FIG. 16A). We used 2× mRNA immunization as a starting point for comparison. Hamsters were first immunized with two doses of mRNA COVID-19 vaccine. 62 days after second dose of mRNA vaccination, hamsters were boosted with mRNA (total 3×mRNA vaccine doses), CVXGA1, CVXGA3, CVXGA14, or PBS. Seventeen days after the third immunization, blood was collected from the hamsters and anti-WA1 S IgG antibodies were quantified via ELISA. Hamsters who received intranasal boosts of CVXGA1 (group 2B), CVXGA13 (group 2C), or CVXGA14 (group 2E) had anti-S IgG titers over 5 log 10, while hamsters who received a mRNA vaccine boost (group 2A) or no boost (group 2D) had lower anti-S IgG titers (FIG. 17A). In neutralization assays with WA1, delta variant, and omicron variant, there was negligible difference in average neutralization titer between sera from hamsters who received a mRNA boost to hamsters who received no boost. However, boosting with mRNA increased detectable levels of neutralizing anti-WA1, delta and omicron from 4, 2 and 3 of 5 animals to 5, 3 and 5 of 5 respectively, indicating that a mRNA boost modestly increased neutralizing antibody responses in the animals (FIG. 17B). In contrast, significant levels of neutralization antibody against WA1, delta variant, and omicron variant were observed in hamsters boosted with CVXGA1, CVXGA13, and CVXGA14 (FIG. 17B).


Twenty-five days following the boost, the hamsters were challenged with delta variant. Hamsters who received intranasal boosts of CVXGA14 or CVXGA1 had the best weight gain compared to hamsters received PBS, no boost, or an mRNA boost. Interestingly, hamsters who received CVXGA14 experienced higher weight gain than hamsters who received CVXGA13 (homologous delta S antigen) (FIG. 17C). Lungs were harvested at five days post-challenge and infectious virus was quantified. None of the boosted hamsters had detectable infectious virus in their lung homogenate (FIG. 17D; LOD, 25 PFU/mL). However, high levels of viral RNA were detected in animals with only two doses of mRNA. CVXGA1-boosted animals had the least amount of viral RNA and mRNA-boosted animals had the most amount of viral RNA among all boosted groups (FIG. 17E).


Example 9: SARS-COV-2 Vaccine Candidates

A number of novel SARS-COV-2 vaccine candidates were rescued as described below and summarized in FIGS. 19A-19B and Table 4.









TABLE 4







SARS-CoV-2 vaccine candidate list












Plasmid

PIV5
virus
SARS-CoV-2 strain, inserted gene
Virus


name
vector
backbone
name
and location, backbone modifications
obtained





pCVL6
pUC
CPI
CVXGA1
S from Wuhan strain inserted between SH and HN (made
Ph1






in UGA lab)



pCVL34
pKBS3
CPI
CVXGA2
S and N from Wuhan strain, S is between SH and HN, N







is between HN and L



pCVL44
pUC
CPI
CVXGA3
S from Beta variant inserted between SH and HN



pCVL48
pUC
CPI
CVXGA4
S from Alpha variant inserted between SH and HN



pCVL49
pUC
CPI
CVXGA5
S from Gamma variant inserted between SH and HN



pCVL50
pUC
CPI
CVXGA6
S from Epsilon variant inserted between SH and HN



pCVL52
pUC
CPI
CVXGA7
N from Wuhan strain, S from Beta variant, N and S are
Plasmid






between F and HN, backbone is CPI lacking SH.
construction


pCVL53
pUC
CPI
CVXGA8
N from Wuhan strain inserted between F and HN,







backbone is CPI lacking SH.



pCVL54
pUC
CPI
CVXGA9
N from Wuhan strain inserted between F and HN, S from







Beta variant inserted between HN and L, backbone is CPI







lacking SH.



pCVL55
pUC
CPI
CVXGA10
S from Beta variant inserted between SH and HN,







backbone is CPI containing S157F and S308A in V/P







gene.



pCVL58
pUC
CPI
CVXGA11
S from Beta variant inserted between F and HN, backbone
Rescue






is CPI lacking SH.



pCVL59
pUC
CPI
CVXGA12
S from Beta variant inserted between F and HN, backbone
Rescue






is CPI lacking SH and containing S157F and S308A in







V/P gene.



pCVL60
pUC
CPI
CVXGA13
S from Delta variant inserted between SH and HN



pCVL64
pUC
CPI
CVXGA26
S from Lambda variant inserted between SH and HN
Rescue


pCVL65
pUC
CPI
CVXGA27
N from Wuhan strain inserted between F and HN, S from
Plasmid






Delta variant inserted between HN and L, backbone is
construction






CPI lacking SH.



pCVL67
pUC
CPI
CVXGA28
S from Mu variant inserted between SH and HN
Plasmid







construction


pCVL80
pUC
CPI
CVXGA14
S from Omicron BA1 strain inserted between SH and HN







in CPI backbone



pCVL86
pUC
CPI
CVXGA15
S from Omicron BA2 strain inserted between SH and HN
rescue






in CPI backbone



pCVL108
pUC
CPI
CVXGA20
S from Omicron BA.5 variant inserted between SH and







HN in CPI backbone



pCVL111
pUC
CPI
CVXGA23
S from Omicron BA.2.75 variant inserted between SH
Plasmid






and HN in CPI backbone
construction


pCVL113
pUC
CPI
CVXGA25
PIV5 F and HN genes are deleted. S from Wuhan strain
Plasmid






inserted between M and L in CPI backbone.
construction









SARAS-COV-2 variants representing variants of concern or variants of interest were produced by inserting the Spike (S) protein gene from different variants into PIV5 canine parainfluenza virus (CPI) vector: CVXGA1, 3, 4, 5, 6, 13, 14, 15, 20, 23, 26, and 28.


To improve vaccine efficacy, the N protein gene of SARS-CoV-2 was inserted between the HN and L gene junction in addition to the S inserted at the SH and HN junction, the resulting virus is named as CVXGA2. The expression of both the S and N proteins of SARS-CoV-2 is expected to offer additional protection by eliciting both antibody and cellular immune responses offered by the N protein. However, CVXGA2's titer is low, further improvement is therefore explored in this disclosure.


The mutations in the V/P gene, S157F and 5308A, have been shown previously to increase viral polymerase activities and improve viral titer or yield (Timani K A, et al., J Virol., 82(18):9123(2008); Sun D, et al., PLoS Pathog., 5(7):e1000525 (2009)). We therefore introduced S157F and 5308A into the CPI V/P gene to produce CVXGA10 (CPI-S-PLK) and CVXGA12 (CPIΔSH-S-PLK) viruses.


The complete disclosure of all patents, patent applications, and publications, and electronically available material (including, for instance, nucleotide sequence submissions in, e.g., GenBank and RefSeq, and amino acid sequence submissions in, e.g., SwissProt, PIR, PRF, PDB, and translations from annotated coding regions in GenBank and RefSeq) cited herein are incorporated by reference. In the event that any inconsistency exists between the disclosure of the present application and the disclosure(s) of any document incorporated herein by reference, the disclosure of the present application shall govern. The foregoing detailed description and examples have been given for clarity of understanding only. No unnecessary limitations are to be understood therefrom. The invention is not limited to the exact details shown and described, for variations obvious to one skilled in the art will be included within the invention defined by the claims.

Claims
  • 1. A viral expression vector comprising a parainfluenza virus 5 (PIV5) genome having a heterologous nucleic acid sequence with at least 98% sequence identity to SEQ ID NOs: 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, or 80, wherein the viral expression vector expresses a heterologous polypeptide comprising a coronavirus spike (S) and/or nucleocapsid (N) proteins.
  • 2. The viral expression vector of claim 1, wherein the coronavirus S protein is a coronavirus S protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a variant of interest or a variant of concern of SARS-CoV-2 and the coronavirus N protein is the coronavirus N protein of SARS-CoV-2, a variant of interest or a variant of concern of SARS-CoV-2.
  • 3. The viral expression vector of claim 1, wherein the coronavirus S protein is the coronavirus S protein of a SARS-CoV-2 beta variant, a SARS-CoV-2 gamma variant, a SARS-CoV-2 delta variant, or a SARS-CoV-2 omicron variant and the coronavirus N protein is the coronavirus N protein of a SARS-CoV-2 beta variant, a SARS-CoV-2 gamma variant, a SARS-CoV-2 delta variant, or a SARS-CoV-2 omicron variant.
  • 4. The viral expression vector of claim 1, wherein the coronavirus S protein comprises the coronavirus S protein of SARS-CoV-2 and wherein the cytoplasmic tail of the coronavirus S protein has been replaced with the cytoplasmic tail of the fusion (F) protein of PIV5.
  • 5. The viral expression vector of claim 1, wherein the coronavirus S protein of a variant of SARS-CoV-2 has been inserted between the PIV5 small hydrophobic (SH) and hemagglutinin (HN) genes and the coronavirus N protein of a variant of SARS-CoV-2 has been inserted between the PIV5 HN and polymerase (L) genes.
  • 6. The viral expression vector of claim 1, wherein the coronavirus S protein of a variant of SARS-CoV-2 has been inserted between the PIV5 HN and polymerase (L) genes.
  • 7. The viral expression vector of claim 1, wherein the coronavirus S protein is a S protein from a variant of interest or a variant of concern of SARS-CoV-2 and the coronavirus N protein is a N protein from different variant of interest or a variant of concern of SARS-CoV-2.
  • 8. The viral expression vector of claim 1, wherein the PIV5 small hydrophobic (SH) gene has been replaced with the coronavirus N protein of SARS-CoV-2.
  • 9. The viral expression vector of claim 1, wherein the PIV5 genome further comprises one or more mutations comprising a mutation of the V/P gene, a mutation of the shared N-terminus of the V and P proteins, a mutation of residues 26, 32, 33, 50, 102, and/or 157 of the shared N-terminus of the V and P proteins, a mutation lacking the C-terminus of the V protein, a mutation lacking the small hydrophobic (SH) protein, a mutation of the fusion (F) protein, a mutation of the phosphoprotein (P), a mutation of the large RNA polymerase (L) protein, a mutation incorporating residues from canine parainfluenza virus, a mutation inducing apoptosis, or a combination thereof.
  • 10. The viral expression vector of claim 9, wherein the one or more mutations comprise PIV5VΔC, PIV5ΔSH, PIV5-P-S308G, or a combination thereof.
  • 11. The viral expression vector of claim 1, wherein the heterologous polypeptide comprises a CPI V/P gene that contains mutations at amino acid residue S157 or S308, or the combination thereof, wherein serine (S) is substituted with an amino acid residue selected from a group consisting of alanine (A), asparagine (B), cysteine (C), aspartic acid (D), glutamic acid (E), phenylalanine (F), glycine (G), histidine (H), isoleucine (I), lysine (K), leucine (L), methionine (M), asparagine (N), proline (P), glutamine (Q), arginine (R), selenocysteine (U), valine (V), tryptophan (W), tyrosine (Y), and glutamine (Z).
  • 12. The viral expression vector of claim 11, wherein the amino acid substitution at amino acid residue S157 comprises a substitution of serine (S) to phenylalanine (F) and the amino acid substitution at amino acid residue S308 comprises a substitution of serine (S) to alanine (A) or Glycine (G).
  • 13. The viral expression vector of claim 1, wherein a viral particle comprises the viral expression vector.
  • 14. A composition comprising a viral expression vector comprising a parainfluenza virus 5 (PIV5) genome having a heterologous nucleic acid sequence with at least 98% sequence identity to SEQ ID NOs: 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, or 80, wherein the viral expression vector expresses a heterologous polypeptide comprising a coronavirus spike (S) and/or nucleocapsid (N) proteins.
  • 15. The composition of claim 14, wherein a heterologous coronavirus spike (S) and nucleocapsid (N) proteins are expressed in a cell by contacting the cell with the composition.
  • 16. A method of inducing an immune response in a subject having coronavirus disease 2019 (COVID-19), the method comprising administering a composition comprising a viral expression vector or a viral particle comprising a parainfluenza virus 5 (PIV5) genome having a heterologous nucleic acid sequence with at least 98% sequence identity to SEQ ID NOs: 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, or 80, wherein the viral expression vector expresses a heterologous polypeptide comprising a coronavirus spike (S) and/or nucleocapsid (N) proteins, andwherein the immune response comprises a humoral immune response and/or a cellular immune response.
  • 17. The method of claim 16, wherein the subject is vaccinated against COVID-19), the method comprising administering the composition to the subject.
  • 18. The method of claim 16, wherein the composition is administered intranasally, intramuscularly, topically, or orally.
  • 19. The method of claim 16, further inducing in a subject an immune response comprising administering a PIV-5 booster vaccine composition comprising a viral expression vector or a viral particle having a PIV5 genome comprising a heterologous nucleic acid sequence with at least 98% sequence identity to SEQ ID NOs: 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, or 80, wherein said subject has previously received a primary vaccination against SARS-COV-2.
REFERENCE TO RELATED APPLICATIONS

This application is the United States non-provisional patent application of U.S. Provisional Application Ser. No. 63/246,161, filed Sep. 20, 2021, and of U.S. Provisional Application Ser. No. 63/365,934, filed Jun. 6, 2022, each of which are hereby incorporated by this reference in their entireties.

Provisional Applications (2)
Number Date Country
63246161 Sep 2021 US
63365934 Jun 2022 US