Patent Application
20060269562
The present invention relates to a novel polypeptide of the hepatitis C virus, derived from a reading frame shift, that is useful in particular in prophylactic and therapeutic immunization directed against this virus.
Hepatitis C is the main cause of hepatitis acquired by transfusion. Hepatitis C can also be transmitted by other percutaneous routes, for example by intravenous drug injection. The risk of contamination among health professionals is not, moreover, insignificant.
Hepatitis C differs from the other forms of liver diseases associated with viruses, such as hepatitis A, B or D. Infections with the hepatitis C virus (HCV) are mainly chronic and result in liver diseases, such as hepatitis, cirrhosis and carcinoma in a large number of cases (5 to 20%).
Although the risk of virus transmission by transfusion has decreased due to the setting up of screening assays in the 1990s, the frequency of hepatitis C remains high. By way of example, a recent study indicates that there are, at this time, still thought to be 10 000 to 15 000 new cases of infection per year in France (S. Deuffic and al., Hepatology 1999; 29: 1596-1601). Currently, approximately 170 million individuals throughout the world are chronically infected with HCV. The high-risk populations are mainly hospital personnel and intravenous drug users, but there are asymptomatic blood donors who do not belong to these high-risk groups and in whom circulating anti-HCV antibodies have been found. For the latter, the route of infection has not yet been identified.
HCV was the first hepatotropic virus isolated by means of molecular biology techniques. The sequences of the viral genome were cloned before the viral particle were visualized.
HCV belongs to a new genus of the family Flaviviridae, the hepaciviruses. It is a positive, single-stranded RNA virus of 9.5 kb that replicates by means of a complementary RNA copy and the translation product of which is a polyprotein precursor of approximately 3 000 amino acids. The 5′ end of the HCV genome corresponds to an untranslated region adjacent to the genes that encode the structural proteins, the core protein of the nucleocapsid, the two envelope glycoproteins, E1 and E2, and a small protein called p7. The 5′ untranslated region and the core gene are relatively well conserved in the various genotypes. The E1 and E2 envelope proteins are encoded by regions that are more variable from one isolate to another. The p7 protein is an extremely hydrophobic protein that is thought to constitute an ion channel. The 3′ end of the HCV genome contains the genes that encode the non-structural proteins (NS2, NS3, NS4 and NS5) and a 3′ noncoding region that has a well conserved domain (Major M E, Feinstone S M, Hepatology, June 1997, 25(6): 1527-1538).
At the current time, the most effective therapy for treating hepatitis C combines pegylated interferon and ribavirin (Manns M P and al., The Lancet, Sep. 22, 2001, Vol. 358, 958-965). Although this therapy is particularly effective in the case of patients infected with viral strains belonging to genotypes 2 and 3, it still has only a limited effect on genotypes 1a, 1b and 4 (Manns M P, above). Less than 50% of patients treated become “long-term responders”.
It is therefore necessary to develop a vaccine composition that targets these “poor responder” genotypes as a priority.
Several studies today show that the control of an infection due to HCV, either naturally (“spontaneous resolution”) or after treatment (“therapeutic resolution”), is associated with the induction or the potentiation of cell-mediated immune responses involving CD4+ T and CD8+ T lymphocytes (Ward S., and al., 2002, Clin. Exp. Immunol., 128: 195-203).
The aim of vaccines based on the use of peptides is generally to induce immune responses mediated by CD4+ T lymphocytes and/or CD8+ T lymphocytes.
The molecules of the major histocompatibility complex (MHC or otherwise called HLA in humans) are referred to as class I or class II. The class I molecules are expressed on virtually all nucleated cells and are capable of presenting epitopes or peptides to CD8+ cytotoxic T lymphocytes (CTLs). The class II molecules are capable of presenting epitopes to CD4+ T cells, but their expression is restricted to antigen-presenting cells.
Patent application WO 99/63941 describes a novel protein of the hepatitis C virus, of 196 amino acids, that is not encoded by a conventional open reading frame of the HCV virus. In fact, this protein is an alternative protein to the core protein of the virus exhibiting a reading frame shift at position +1 or +2. That application also describes two peptides of 13 amino acids derived from this novel protein, which contain B epitopes and are therefore useful in particular for the production of antibodies for diagnosis. No cell-mediated response is shown in that document.
Z. Xu and al. (Xu, Z. et al., 2001, EMBO J., 20(14), 3840-3848), J. L. Walewski, and al. (2001, RNA, 7, 710-721) and also Varaklioti et al. (2001, J. Biol. Chem., 20(17), 17713-17721) confirm this open reading frame shift within the core protein. In these articles, the experiments described were carried ort essentially in vitro, with the exception of preliminary assays using sera from patients carrying HCV. These preliminary assays refer to the presence of antibodies specific for this novel alternative core protein, called protein F, in patients carrying HCV. These studies are focused on viral strains of genotype 1a.
None of these documents of the prior art either describes or suggests the existence of cell-mediated responses specific for this novel protein F in patients carrying HCV.
The applicant has demonstrated, unexpectedly, a novel polypeptide of 99 amino acids that induces a cell-mediated response in patients who are seropositive for HCV, and in particular the secretion of interleukin 10 (IL10), with or without production of gamma-interferon, and that is capable of inducing specific cellular immune responses in patients infected with viral strains, in particular of genotypes 1b and 3, whatever the HLA typing of the patient, but preferably for HLA-A2 and B7 patients.
As this polypeptide is a fragment of the protein F, it was called polypeptide F′.
Thus, a subject of the present invention is a polypeptide F′ that induces an immune response against the hepatitis C virus, characterized in that it consists of 99 amino acids located between positions 43 and 141 of the polyprotein of the hepatitis C virus.
Of course, the expression “located between positions 43 and 141 of the polyprotein of the hepatitis C virus” is intended to mean positions 43 to 141 of the polyprotein encoded with a shift of +1 on the reading frame, as previously indicated for the protein F. This nomenclature will subsequently be used for the positions with respect to the polyprotein of the virus.
A subject of the invention is also four particular T epitopes that are at least partially included in this protein F′, located at positions 40-48, 43-51, 50-58 and 73-81 of the HCV polyprotein, which epitopes induce an immune response, the nucleotide sequences encoding said proteins and said epitopes, the vectors that include these nucleotide sequences, and also the microorganisms or host cells cotransformed with these vectors.
Finally, a subject of the invention is also the antibodies directed against the polypeptides and epitopes of the invention, and also the use of the polypeptides, of the epitopes and of the antibodies, for preparing a drug intended to inhibit or prevent an infection caused by the hepatitis C virus, and also for preparing diagnostic compositions.
The polypeptides F′, and also the epitopes of the invention, are capable, unexpectedly, of inducing a cell-mediated response in patients who are seropositive for HCV, and in particular the secretion of interleukin 10 (IL10), with or without production of gamma-interferon.
The polypeptides F′ and epitopes were obtained from the Shimotono genotype 1b consensus sequence (EMBL D89872).
The polypeptides F′ have 99 amino acids, located at positions 43 and 141 of the hepatitis C virus poly-protein.
Throughout the remainder of the text, the term “polypeptide” or “epitope” will of course be intended to mean the polypeptides and epitopes having the natural amino acid sequences, originating from any strain and isolate of HCV, as defined in the sequence listing, and also the analogs, muteins and homologs thereof.
The epitopes are peptides that have approximately from 8 to 15 amino acids and the polypeptides are larger peptides, such that, in the definitions hereinafter, the term “peptide” will be used indifferently to denote an epitope or a polypeptide.
The terms “analogs” or “muteins” of a peptide is intended to mean the biologically active derivatives of the reference molecules that exhibit the desired activity, namely the ability to stimulate a cell-mediated immune response as defined above.
In general, the term “analog” refers to compounds that have a natural sequence and polypeptide structure exhibiting one or more amino acid additions, substitutions (generally conservative in terms of nature) and/or deletions relative to the natural molecule, provided that the modifications do not destroy the immunogenic activity. The term “mutein” is intended to mean the peptides having one or more elements that imitate the peptide (“peptoids”), such as those described in PCT patent application WO 91/04282. Preferably, the analog or the mutein has at least the same immunoactivity as the natural molecule. Methods for preparing polypeptide analogs and muteins are known to those skilled in the art and are described below.
The analogs that are particularly preferred include the substitutions that are conservative in nature, i.e. the substitutions that take place in a family of amino acids. Specifically, amino acids are generally divided up into 4 families, i.e. (1) acidic amino acids such as aspartate and glutamate, (2) basic amino acids such as lysine, arginine and histidine, (3) nonpolar amino acids such as alanine, leucine, isoleucine, proline, phenylalanine, methionine and tryptophan, and (4) uncharged polar amino acids such as glycine, asparagine, glutamine, cysteine, serine, threonine and tyrosine. Phenylalanine, tryptophan and tyrosine are sometimes classified as aromatic amino acids. For example, it can reasonably be predicted that the isolated replacement of leucine with isoleucine or valine, of an aspartate with a glutamate, or of a threonine with a serine, or a similar conservative replacement of an amino acid with another amino acid that is structurally related, will have no major effect on the biological activity. Those skilled in the art will readily determine the regions of the peptide molecule of interest that can tolerate a change with reference to the Hopp/Woods and Kyte-Doolite plots, that are well known in the art.
The term “homology” is intended to mean the percentage of identity between two peptide molecules. Two amino acid sequences are “substantially homologous” to one another when the sequences exhibit at least 60%, preferably at least 75%, more preferably at least 80-85%, more preferably at least 90%, and even more preferably at least 95-98% or more, sequence identity over a defined length of the peptide molecules.
In general, the term “identity” refers to an exact correspondence amino acid by amino acid of two peptide sequences. The percentage identity can be determined by direct comparison of the sequence information between two molecules by aligning the sequences, counting the exact number of mismatches between the two aligned sequences, dividing by the length of the shortest sequence, and multiplying the result by 100. The percentage identity can also be determined using computer programs such as ALIGN, M. O. Dayhoff, in Atlas of Protein Sequence and Structure M. O. Dayhoff ed., 1981, 5 Suppl., 3: 482-489.
According to a particular embodiment of the invention, the polypeptides F′ are derived from genotype 1b of HCV and have the sequence SEQ ID No.1 below: X1WVCX2X3X4X5RLPSGX6NX7X8X9X10X11X12LX13X14RX15X16X17PRX18GX19GX20SX21GX22X23GX24 SX25X26X27RX28X29X30GX31DGSCX32 PX33X34X35GLX36GAX37X38TPX39X40GX41X42X43WVX44SSX45X46X47X48X49X50X51PX52SWGX53X54RX55SX56, in which X1 is G, D, E, V or S, X2 is A or V, X3 is R, H or Q, X4 is L, R, P, S or G, X5 is G or E, X6 is R, L or H, X7 is L or P, X8 is V, E or A, X9 is E, V, D or G, X10 is G or D, X11 is D or V, X12 is N or S, X13 is S or F, X14 is P or Q, X15 is L, H, R, F, P or C, X16 is A, V or I, X17 is G, S, D, N, I or V, X18 is A, V or E, X19 is P, S or T, X20 is L, P, H or R, X21 is P or L, X22 is T or I, X23 is L, P or H, X24 is P or L, X25 is M or T, X26 is A, V or P, X27 is M, I or T, X28 is A or V, X29 is W, A, L or V, X30 is G or D, X31 is Q, L or R, X32 is H, L, P or R, X33 is V, A, E, K or T, X34 is A or V, X35 is L, R, H or P, X36 is V, A, I or G, X37 is P or L, X38 is R, Q, L, M, T, E or P, X39 is G or D, X40 is V, A or G, X41 is R or H, X42 is V or A, X43 is I or T, X44 is R, G or K, X45 is I or T, X46 is P or L, X47 is S or L, X48 is H or R, X49 is A or V, X50 is A, V or G, X51 is S or L, X52 is T or I, X53 is T or I, X54 is F, Y or S, X55 is S or L and X56 is A, V, G or H.
Preferably, the polypeptide F′ is chosen from the following polypeptides:
the polypeptide of sequence SEQ ID No.2 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.3 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is V, X35 is L, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is K, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is S, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.4 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is S, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.5 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is L, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is T, X44 is K, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.6 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is V, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is L, X22 is I, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is L, X38 is M, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is S, X55 is L and X56 is A,
the polypeptide of sequence SEQ ID No.7 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is V, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is L, X22 is I, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is M, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.8 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is I, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is A, X37 is L, X38 is P, X39 is G, X40 is V, X41 is R, X42 is V, X43 is T, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.9 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is L, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.10 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is L, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.11 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is H, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is F, X14 is P, X15 is L, X16 is V, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is E, X34 is A, X35 is L, X36 is V, X37 is P, X38 is L, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.12 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is T, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.13 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is M, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.14 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is A, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is A, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.15 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is N, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is A, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.16 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is H, X7 is L, X8 is A, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is I, X18 is A, X19 is P, X20 is L, X21 is L, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is L, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.17 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is H, X7 is L, X8 is A, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is I, X18 is A, X19 is P, X20 is L, X21 is L, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is R, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is L, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.18 which corresponds to the sequence SEQ ID No.1 in which X1 is V, X2 is A, X3 is R, X4 is L, X5 is G, X6 is H, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is F, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is L, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is L, X39 is G, X40 is V, X41 is R, X42 is A, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is I, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.19 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is H, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is T, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.20 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is F, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is T, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is T, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is I, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.21 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is T, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.22 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is F, X16 is A, X17 is D, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is P, X27 is T, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is A, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is R, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.23 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is D, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is P, X27 is T, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is E, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is A, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.24 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is V, X27 is T, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is E, X34 is A, X35 is L, X36 is A, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is R, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.25 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is D, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is E, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is A, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.26 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is G, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is L and X56 is A,
the polypeptide of sequence SEQ ID No.27 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is T, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is E, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is L and X56 is A,
the polypeptide of sequence SEQ ID No.28 which corresponds to the sequence SEQ ID No.1 in which X1 is S, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is P, X21 is P, X22 is T, X23 is P, X24 is P, X25 is M, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is E, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.29 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is F, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is I, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is G, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.30 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is F, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is G, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is G, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.31 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is L and X56 is A,
the polypeptide of sequence SEQ ID No.32 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is I, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is L and X56 is A,
the polypeptide of sequence SEQ ID No.33 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is H, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is R, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is A, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is L and X56 is A,
the polypeptide of sequence SEQ ID No.34 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is G, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is A, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is V, X18 is E, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is V, X29 is W, X30 is G, X31 is L, X32 is H, X33 is E, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.35 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is E, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.36 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is E, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is Q, X49 is V, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.37 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is P, X24 is P, X25 is M, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is A, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.38 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is P, X24 is P, X25 is M, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is A, X41 is R, X42 is V, X43 is I, X44 is G, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.39 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X1o is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is P, X24 is P, X25 is M, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.40 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is L, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is T, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.41 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is L, X25 is M, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is R, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.42 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is L, X25 is M, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is R, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.43 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is L and X56 is A,
the polypeptide of sequence SEQ ID No.44 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.45 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is D, X18 is A, X19 is P, X20 is L, X21 is P, X22 is I, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is L, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.46 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is D, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is I, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.47 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is D, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is D, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is T, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is I, X53 is I, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.48 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is Q, X15 is L, X16 is A, X17 is D, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is T, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is I, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.49 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is V, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is Q, X15 is L, X16 is A, X17 is D, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is T, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is I, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.50 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is N, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is I, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.51 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is V, X17 is D, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.52 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is N, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is I, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.53 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is N, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.54 which corresponds to the sequence SEQ ID No.1 in which X1 is G, X2 is A, X3 is R, X4 is P, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is L, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is I, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.55 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is T, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.56 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is S, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is P, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.57 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is S, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is K, X34 is A, X35 is L, X36 is V, X37 is P, X38 is E, X39 is G, X40 is V, X41 is R, X42 is V, X43 is T, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.58 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is S, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.59 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is S, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is H, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No.60 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is S, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is T, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No61 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is S, X5 is G, X6 is R, X7 is P, X8 is V, X9 is E, X10 is G, X11 is D, X12 is S, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is I, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No62 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is S, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No63 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is I, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is R, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No64 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is I, X23 is L, X24 is P, X25 is T, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is V, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No65 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is R, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is I, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No66 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is S, X13 is S, X14 is P, X15 is L, X16 is A, X17 is N, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is L, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is T, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is L and X56 is A,
the polypeptide of sequence SEQ ID No67 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is S, X13 is S, X14 is P, X15 is L, X16 is A, X17 is N, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is L, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is T, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No68 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is S, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No69 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is F, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No70 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No71 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is I, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No72 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is P, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is S, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No73 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No74 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No75 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X1O is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is V, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No76 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is T, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is L and X56 is A,
the polypeptide of sequence SEQ ID No77 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is T, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is L and X56 is A,
the polypeptide of sequence SEQ ID No78 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is T, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is L and X56 is A,
the polypeptide of sequence SEQ ID No79 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is M, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is L and X56 is A,
the polypeptide of sequence SEQ ID No80 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is H, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is L and X56 is A,
the polypeptide of sequence SEQ ID No81 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is H, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No82 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is H, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No83 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is V, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No84 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No85 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is P, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No86 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is L and X56 is A,
the polypeptide of sequence SEQ ID No87 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No88 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is Q, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is P, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is V, X27 is T, X28 is A, X29 is W, X30 is D, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is L, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No89 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is S, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is V, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is I, X37 is L, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No90 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is V, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is D, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is V, X27 is I, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is P, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is M, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is V, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No91 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is I, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No92 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is I, X23 is P, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No93 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is A, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is H, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No94 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No95 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is R, X5 is G, X6 is R, X7 is L, X8 is L, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is E, X34 is A, X35 is L, X36 is I, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is K, X45 is T, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No96 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is I, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is K, X45 is T, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is S, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No97 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is K, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No98 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is R, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is P, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No99 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is G, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No100 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is G, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is G,
the polypeptide of sequence SEQ ID No101 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is F, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is L, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is M, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No102 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is L, X33 is A, X34 is A, X35 is H, X36 is V, X37 is P, X38 is M, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No103 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is V, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No104 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No105 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is H, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is P, X33 is V, X34 is A, X35 is L, X36 is I, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No106 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is L, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is H, X24 is P, X25 is T, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is P, X33 is V, X34 is A, X35 is P, X36 is A, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No107 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is T, X26 is A, X27 is M, X28 is A, X29 is W, X30 is D, X31 is R, X32 is P, X33 is V, X34 is V, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No108 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is L, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is V, X29 is W, X30 is D, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is T, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No109 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is L, X22 is T, X23 is P, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is D, X31 is Q, X32 is P, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is L, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No110 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is T, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is L, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is S, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No111 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is P, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is T, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is L, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is S, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No112 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is I, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is T, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is S, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No113 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is T, X26 is P, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is P, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is T, X46 is P, X47 is P, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No114 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is Q, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is I, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is T, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is M, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is L, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No115 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is T, X20 is L, X21 is P, X22 is I, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No116 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is D, X18 is A, X19 is T, X20 is L, X21 is P, X22 is I, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is R, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No117 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is T, X20 is L, X21 is P, X22 is I, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is F, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No118 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is P, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is K, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No119 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is N, X18 is A, X19 is S, X20 is L, X21 is P, X22 is T, X23 is P, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No120 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is P, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No121 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is I, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No122 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is F, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No123 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No124 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No125 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is P, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is T, X34 is A, X35 is P, X36 is G, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is G,
the polypeptide of sequence SEQ ID No126 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, Xi9 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is T, X34 is A, X35 is P, X36 is G, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No127 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is T, X34 is A, X35 is P, X36 is G, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No128 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is S, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No129 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is H, X7 is L, X8 is V, X9 is A, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is S, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No130 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is A, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is S, X55 is S and X56 is V,
the polypeptide of sequence SEQ ID No131 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is P, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is N, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is V, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No132 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is S, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is D, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is V, X35 is L, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No133 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is H, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is V, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is E, X34 is A, X35 is P, X36 is I, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No134 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is N, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is P, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is E, X34 is A, X35 is P, X36 is I, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No135 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is N, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is I, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No136 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is I, X18 is A, X19 is P, X20 is L, X21 is L, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is A, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is R, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No137 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is V, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is A, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is R, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is L and X56 is A,
the polypeptide of sequence SEQ ID No138 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is V, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is A, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is R, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No139 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is H, X7 is L, X8 is V, X9 is D, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is A, X19 is P, X20 is P, X21 is P, X22 is I, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is A, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is R, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No140 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is R, X22 is I, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is R, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is V,
the polypeptide of sequence SEQ ID No141 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is P, X21 is P, X22 is I, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is A, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is R, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No142 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is P, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is D, X18 is A, X19 is P, X20 is L, X21 is P, X22 is I, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is M, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is V, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is R, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is S, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No143 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is P, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is N, X18 is A, X19 is P, X20 is L, X21 is P, X22 is I, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is L, X36 is I, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is A, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is R, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is S, X55 is S and X56 is V,
the polypeptide of sequence SEQ ID No144 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is P, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is A, X35 is L, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is A, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is R, X49 is A, X50 is A, X51 is S, X52 is I, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No145 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is H, X24 is P, X25 is M, X26 is A, X27 is M, X28 is V, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is V, X34 is D, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is A, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No146 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is A, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is G, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is P, X27 is M, X28 is A, X29 is W, X30 is G, X31 is R, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is V, X41 is R, X42 is A, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No147 which corresponds to the sequence SEQ ID No1 in which X1 is G, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is S, X18 is A, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is P, X39 is G, X40 is V, X41 is R, X42 is A, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is R, X49 is V, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No148 which corresponds to the sequence SEQ ID No1 in which X1 is R, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is D, X18 is V, X19 is P, X20 is L, X21 is L, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is A, X41 is R, X42 is A, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is R, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A,
the polypeptide of sequence SEQ ID No149 which corresponds to the sequence SEQ ID No1 in which X1 is R, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is E, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is D, X18 is V, X19 is P, X20 is L, X21 is L, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is M, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is R, X39 is G, X40 is G, X41 is R, X42 is A, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is R, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A, and
the polypeptide of sequence SEQ ID No150 which corresponds to the sequence SEQ ID No1 in which X1 is S, X2 is A, X3 is R, X4 is L, X5 is G, X6 is R, X7 is L, X8 is V, X9 is G, X10 is G, X11 is D, X12 is N, X13 is S, X14 is P, X15 is L, X16 is A, X17 is N, X18 is V, X19 is P, X20 is L, X21 is P, X22 is T, X23 is L, X24 is P, X25 is M, X26 is A, X27 is T, X28 is A, X29 is W, X30 is G, X31 is Q, X32 is H, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is Q, X39 is G, X40 is V, X41 is H, X42 is A, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is R, X49 is V, X50 is A, X51 is S, X52 is T, X53 is T, X54 is F, X55 is S and X56 is A.
Preferably, the polypeptide F′ of the invention is the polypeptide of sequence SEQ ID No.2.
According to another embodiment of the invention, the polypeptides F′ are derived from genotype 3 of HCV and have the sequence SEQ ID No.151 below:
X1WVCX2X3X4X5X57LX58X59X60X6X61X7AX9X10X11X12X62X13PX63X15X16X17X64X65X18X66PGX20SX21GTX23GX24X67X25X26X27RAX29X30X68X31X69GX70CX32X71X33X34X35X72X73X36GX74X37X38TPGX40X75X41AX43X76X44SSX45X46X47X48X49X50 X51X78X52SWGX53X54RSX79X56,
in which
X1 is D, N, S, Y or G, X2 is A or V, X3 is R, Q, K or L, X4 is R, Y, C, F, H, L or P, X5 is V, A or T, X6 is H, R or Q, X7 is L or P, X9 is D, V, N, R or T, X10 is G, D or S, X11 is D, V, A, G or E, X12 is S, N or T, X13 is S, P or F, X15 is R, H or L, X16 is V or A, X17 is G, R, E, H or V, X18 is A or D, X20 is L, P or R, X21 is P or L, X23 is L or P, X24 is P or L, X25 is M or T, X26 is V, G, A or E, X27 is M, T or I, X29 is A or V, X30 is G, V or D, X31 is Q or R, X32 is P or L, X33 is A or V, X34 is A or V, X35 is P or L, X36 is L, A, V, R, I or P, X37 is Q, K or P, X38 is M or T, X40 is V, G, D, E or A, X41 is P, H or L, X43 is I or T, X44 is R or K, X45 is I or T, X46 is P or L, X47 is S or L, X48 is R or H, X49 is A or V, X50 is D, G, A or V, X51 is S or L, X52 is T, I or A, X53 is T or I, X54 is F or S, X56 is A or V, X57 is K, R or N, X58 is L, P or Q, X59 is S or N, X60 is G or D, X61 is S or N, X62 is L or P, X63 is R or G, X64 is A, P or L, X65 is R, K, E or T, X66 is G or D, X67 is S, Y or F, X68 is G or W, X69 is G or D, X70 is S or F, X71 is P, H, R or L, X72 is V, A, D or G, X73 is H, L, P, Q or R, X74 is A or P, X75 is G or D, X76 is W or L, X77 is V or A, X78 is P or L and X79 is S, L or Q.
Preferably, the polypeptide F′ is chosen from the following polypeptides:
the polypeptide of sequence SEQ ID No152 which corresponds to the sequence SEQ ID No151 in which X1 is D, X2 is A, X3 is R, X4 is R, X5 is V, X6 is H, X7 is L, X9 is D, X10 is G, X11 is D, X12 is S, X13 is S, X15 is R, X16 is V, X17 is G, X18 is A, X20 is L, X21 is P, X23 is L, X24 is P, X25 is M, X26 is V, X27 is M, X29 is A, X30 is G, X31 is Q, X32 is P, X33 is A, X34 is A, X35 is P, X36 is L, X37 is Q, X38 is M, X40 is V, X41 is P, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is R, X49 is A, X50 is D, X51 is S, X52 is T, X53 is T, X54 is F, X56 is A, X57 is K, X58 is L, X59 is S, X60 is G, X61 is S, X62 is L, X63 is R, X64 is A, X65 is R, X66 is G, X67 is S, X68 is G, X69 is G, X70 is S, X71 is P, X72 is V, X73 is H, X74 is A, X75 is G, X76 is W, X77 is V, X78 is P and X79 is S,
the polypeptide of sequence SEQ ID No153 which corresponds to the sequence SEQ ID No151 in which X1 is D, X2 is A, X3 is R, X4 is R, X5 is V, X6 is H, X7 is L, X9 is D, X10 is D, X11 is D, X12 is S, X13 is S, X15 is R, X16 is V, X17 is G, X18 is A, X20 is L, X21 is P, X23 is L, X24 is P, X25 is M, X26 is V, X27 is T, X29 is A, X30 is G, X31 is Q, X32 is P, X33 is A, X34 is A, X35 is P, X36 is P, X37 is Q, X38 is M, X40 is G, X41 is P, X43 is I, X44 is K, X45 is I, X46 is P, X47 is L, X48 is R, X49 is A, X50 is D, X51 is S, X52 is T, X53 is T, X54 is S, X56 is A, X57 is K, X58 is L, X59 is N, X60 is G, X61 is S, X62 is L, X63 is R, X64 is A, X65 is K, X66 is G, X67 is S, X68 is G, X69 is G, X70 is S, X71 is H, X72 is V, X73 is H, X74 is A, X75 is G, X76 is W, X77 is V, X78 is P and X79 is S.
the polypeptide of sequence SEQ ID No154 which corresponds to the sequence SEQ ID No151 in which X1 is D, X2 is A, X3 is R, X4 is P, X5 is V, X6 is H, X7 is L, X9 is D, X10 is D, X11 is D, X12 is S, X13 is S, X15 is R, X16 is V, X17 is G, X18 is A, X20 is L, X21 is P, X23 is L, X24 is P, X25 is M, X26 is V, X27 is T, X29 is A, X30 is G, X31 is Q, X32 is P, X33 is A, X34 is A, X35 is L, X36 is L, X37 is Q, X38 is M, X40 is G, X41 is P, X43 is I, X44 is K, X45 is I, X46 is P, X47 is L, X48 is R, X49 is A, X50 is D, X51 is S, X52 is T, X53 is T, X54 is S, X56 is A, X57 is K, X58 is L, X59 is N, X60 is G, X61 is S, X62 is L, X63 is R, X64 is A, X65 is T, X66 is G, X67 is S, X68 is G, X69 is G, X70 is S, X71 is H, X72 is V, X73 is H, X74 is A, X75 is G, X76 is W, X77 is V, X78 is P and X79 is S,
the polypeptide of sequence SEQ ID No155 which corresponds to the sequence SEQ ID No151 in which X1 is D, X2 is A, X3 is R, X4 is R, X5 is V, X6 is H, X7 is P, X9 is D, X10 is D, X11 is D, X12 is S, X13 is S, X15 is R, X16 is V, X17 is R, X18 is A, X20 is L, X21 is P, X23 is L, X24 is P, X25 is M, X26 is V, X27 is M, X29 is A, X30 is G, X31 is Q, X32 is P, X33 is A, X34 is A, X35 is P, X36 is L, X37 is Q, X38 is M, X40 is G, X41 is P, X43 is I, X44 is K, X45 is I, X46 is P, X47 is L, X48 is R, X49 is V, X50 is D, X51 is S, X52 is T, X53 is T, X54 is S, X56 is A, X57 is K, X58 is L, X59 is N, X60 is G, X61 is S, X62 is L, X63 is R, X64 is A, X65 is E, X66 is G, X67 is S, X68 is G, X69 is G, X70 is S, X71 is R, X72 is V, X73 is H, X74 is A, X75 is G, X76 is W, X77 is V, X78 is P and X79 is S,
the polypeptide of sequence SEQ ID No156 which corresponds to the sequence SEQ ID No151 in which X1 is D, X2 is A, X3 is R, X4 is R, X5 is V, X6 is R, X7 is L, X9 is D, X10 is D, X11 is D, X12 is S, X13 is S, X15 is R, X16 is V, X17 is G, X18 is A, X20 is L, X21 is P, X23 is L, X24 is P, X25 is M, X26 is V, X27 is T, X29 is A, X30 is G, X31 is Q, X32 is P, X33 is A, X34 is A, X35 is P, X36 is L, X37 is Q, X38 is T, X40 is D, X41 is P, X43 is I, X44 is K, X45 is I, X46 is P, X47 is L, X48 is R, X49 is A, X50 is D, X51 is S, X52 is T, X53 is T, X54 is S, X56 is A, X57 is K, X58 is L, X59 is N, X60 is G, X61 is S, X62 is L, X63 is R, X64 is A, X65 is K, X66 is G, X67 is S, X68 is G, X69 is D, X70 is S, X71 is H, X72 is V, X73 is H, X74 is A, X75 is G, X76 is W, X77 is V, X78 is P and X79 is S.
the polypeptide of sequence SEQ ID No157 which corresponds to the sequence SEQ ID No151 in which X1 is D, X2 is A, X3 is R, X4 is R, X5 is V, X6 is H, X7 is L, X9 is D, X10 is D, X11 is G, X12 is S, X13 is S, X15 is R, X16 is V, X17 is G, X18 is A, X20 is L, X21 is P, X23 is L, X24 is P, X25 is M, X26 is V, X27 is T, X29 is A, X30 is G, X31 is Q, X32 is P, X33 is A, X34 is A, X35 is P, X36 is L, X37 is Q, X38 is M, X40 is D, X41 is P, X43 is I, X44 is K, X45 is I, X46 is P, X47 is L, X48 is R, X49 is A, X50 is D, X51 is S, X52 is T, X53 is T, X54 is S, X56 is A, X57 is K, X58 is L, X59 is N, X60 is G, X61 is S, X62 is L, X63 is R, X64 is A, X65 is K, X66 is G, X67 is S, X68 is G, X69 is D, X70 is S, X71 is R, X72 is V, X73 is H, X74 is A, X75 is G, X76 is W, X77 is V, X78 is P and X79 is S.
the polypeptide of sequence SEQ ID No158 which corresponds to the sequence SEQ ID No151 in which X1 is D, X2 is A, X3 is R, X4 is R, X5 is V, X6 is H, X7 is L, X9 is D, X10 is D, X11 is D, X12 is S, X13 is S, X15 is H, X16 is V, X17 is G, X18 is A, X20 is L, X21 is L, X23 is L, X24 is P, X25 is M, X26 is V, X27 is T, X29 is A, X30 is G, X31 is Q, X32 is P, X33 is A, X34 is A, X35 is P, X36 is L, X37 is Q, X38 is T, X40 is D, X41 is P, X43 is I, X44 is K, X45 is I, X46 is P, X47 is L, X48 is R, X49 is A, X50 is D, X51 is S, X52 is T, X53 is T, X54 is S, X56 is A, X57 is K, X58 is L, X59 is N, X60 is G, X61 is S, X62 is L, X63 is R, X64 is A, X65 is K, X66 is G, X67 is S, X68 is G, X69 is G, X70 is S, X71 is H, X72 is V, X73 is H, X74 is A, X75 is G, X76 is W, X77 is V, X78 is P and X79 is S,
the polypeptide of sequence SEQ ID No159 which corresponds to the sequence SEQ ID No151 in which X1 is D, X2 is A, X3 is R, X4 is R, X5 is V, X6 is H, X7 is L, X9 is D, X10 is D, X11 is D, X12 is S, X13 is S, X15 is R, X16 is V, X17 is G, X18 is A, X20 is L, X21 is P, X23 is L, X24 is P, X25 is M, X26 is V, X27 is T, X29 is A, X30 is G, X31 is Q, X32 is P, X33 is A, X34 is A, X35 is P, X36 is L, X37 is Q, X38 is T, X40 is G, X41 is P, X43 is I, X44 is K, X45 is I, X46 is P, X47 is L, X48 is R, X49 is A, X50 is V, X51 is S, X52 is T, X53 is T, X54 is S, X56 is A, X57 is K, X58 is L, X59 is N, X60 is G, X61 is S, X62 is L, X63 is R, X64 is A, X65 is K, X66 is G, X67 is S, X68 is G, X69 is G, X70 is S, X71 is H, X72 is V, X73 is Q, X74 is A, X75 is G, X76 is W, X77 is V, X78 is P and X79 is S,
the polypeptide of sequence SEQ ID No160 which corresponds to the sequence SEQ ID No151 in which X1 is D, X2 is A, X3 is R, X4 is R, X5 is V, X6 is H, X7 is L, X9 is D, X10 is D, X11 is D, X12 is S, X13 is S, X15 is R, X16 is V, X17 is G, X18 is A, X20 is L, X21 is P, X23 is L, X24 is P, X25 is M, X26 is V, X27 is M, X29 is A, X30 is G, X31 is Q, X32 is P, X33 is A, X34 is A, X35 is P, X36 is L, X37 is Q, X38 is T, X40 is G, X41 is P, X43 is I, X44 is K, X45 is I, X46 is P, X47 is L, X48 is R, X49 is A, X50 is D, X51 is S, X52 is T, X53 is T, X54 is S, X56 is A, X57 is K, X58 is L, X59 is N, X60 is G, X61 is S, X62 is L, X63 is R, X64 is A, X65 is K, X66 is G, X67 is S, X68 is G, X69 is G, X70 is S, X71 is H, X72 is V, X73 is H, X74 is A, X75 is G, X76 is W, X77 is V, X78 is P and X79 is S,
the polypeptide of sequence SEQ ID No161 which corresponds to the sequence SEQ ID No151 in which X1 is D, X2 is A, X3 is R, X4 is R, X5 is V, X6 is H, X7 is L, X9 is D, X10 is G, X11 is D, X12 is S, X13 is S, X15 is R, X16 is V, X17 is G, X18 is A, X20 is L, X21 is P, X23 is L, X24 is P, X25 is M, X26 is V, X27 is T, X29 is A, X30 is G, X31 is Q, X32 is P, X33 is A, X34 is A, X35 is P, X36 is L, X37 is Q, X38 is M, X40 is G, X41 is P, X43 is I, X44 is K, X45 is I, X46 is P, X47 is L, X48 is R, X49 is A, X50 is A, X51 is S, X52 is T, X53 is T, X54 is S, X56 is A, X57 is K, X58 is L, X59 is N, X60 is G, X61 is S, X62 is L, X63 is R, X64 is A, X65 is K, X66 is D, X67 is S, X68 is G, X69 is G, X70 is S, X71 is H, X72 is V, X73 is H, X74 is A, X75 is G, X76 is W, X77 is V, X78 is P and X79 is S,
the polypeptide of sequence SEQ ID No162 which corresponds to the sequence SEQ ID No151 in which X1 is D, X2 is A, X3 is R, X4 is R, X5 is V, X6 is H, X7 is L, X9 is D, X10 is G, X11 is D, X12 is S, X13 is S, X15 is R, X16 is V, X17 is G, X18 is A, X20 is L, X21 is P, X23 is L, X24 is P, X25 is M, X26 is V, X27 is T, X29 is A, X30 is G, X31 is Q, X32 is P, X33 is A, X34 is A, X35 is L, X36 is L, X37 is K, X38 is M, X40 is G, X41 is P, X43 is T, X44 is R, X45 is I, X46 is P, X47 is L, X48 is R, X49 is A, X50 is D, X51 is S, X52 is T, X53 is T, X54 is S, X56 is A, X57 is K, X58 is L, X59 is N, X60 is G, X61 is S, X62 is L, X63 is R, X64 is A, X65 is K, X66 is G, X67 is S, X68 is G, X69 is G, X70 is S, X71 is R, X72 is V, X73 is H, X74 is A, X75 is G, X76 is W, X77 is A, X78 is P and X79 is S,
the polypeptide of sequence SEQ ID No163 which corresponds to the sequence SEQ ID No151 in which X1 is D, X2 is A, X3 is R, X4 is R, X5 is V, X6 is H, X7 is L, X9 is D, X10 is G, X11 is D, X12 is S, X13 is S, X15 is R, X16 is V, X17 is G, X18 is A, X20 is L, X21 is L, X23 is L, X24 is P, X25 is M, X26 is V, X27 is T, X29 is A, X30 is G, X31 is Q, X32 is P, X33 is A, X34 is A, X35 is P, X36 is L, X37 is Q, X38 is T, X40 is G, X41 is P, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is R, X49 is A, X50 is D, X51 is S, X52 is T, X53 is T, X54 is S, X56 is A, X57 is K, X58 is L, X59 is N, X60 is G, X61 is S, X62 is L, X63 is R, X64 is A, X65 is K, X66 is G, X67 is S, X68 is G, X69 is G, X70 is S, X71 is H, X72 is V, X73 is H, X74 is A, X75 is G, X76 is W, X77 is V, X78 is P and X79 is S,
the polypeptide of sequence SEQ ID No164 which corresponds to the sequence SEQ ID No151 in which X1 is D, X2 is A, X3 is R, X4 is R, X5 is V, X6 is R, X7 is L, X9 is D, X10 is G, X11 is E, X12 is S, X13 is S, X15 is R, X16 is V, X17 is G, X18 is A, X20 is P, X21 is L, X23 is L, X24 is P, X25 is M, X26 is V, X27 is M, X29 is A, X30 is G, X31 is Q, X32 is P, X33 is A, X34 is A, X35 is P, X36 is I, X37 is Q, X38 is M, X40 is D, X41 is P, X43 is I, X44 is K, X45 is I, X46 is P, X47 is S, X48 is R, X49 is A, X50 is D, X51 is S, X52 is I, X53 is T, X54 is S, X56 is A, X57 is K, X58 is L, X59 is N, X60 is G, X61 is S, X62 is L, X63 is R, X64 is A, X65 is K, X66 is G, X67 is S, X68 is G, X69 is G, X70 is S, X71 is H, X72 is V, X73 is Q, X74 is P, X75 is G, X76 is W, X77 is V, X78 is P and X79 is S,
the polypeptide of sequence SEQ ID No165 which corresponds to the sequence SEQ ID No151 in which X1 is D, X2 is A, X3 is Q, X4 is L, X5 is V, X6 is H, X7 is P, X9 is D, X10 is G, X11 is D, X12 is S, X13 is F, X15 is H, X16 is A, X17 is R, X18 is D, X20 is R, X21 is L, X23 is P, X24 is P, X25 is M, X26 is V, X27 is T, X29 is A, X30 is G, X31 is Q, X32 is L, X33 is A, X34 is A, X35 is P, X36 is V, X37 is P, X38 is T, X40 is E, X41 is P, X43 is I, X44 is R, X45 is T, X46 is L, X47 is S, X48 is H, X49 is A, X50 is G, X51 is S, X52 is I, X53 is I, X54 is F, X56 is A, X57 is R, X58 is Q, X59 is S, X60 is G, X61 is N, X62 is L, X63 is R, X64 is A, X65 is E, X66 is G, X67 is S, X68 is G, X69 is G, X70 is F, X71 is L, X72 is D, X73 is R, X74 is A, X75 is G, X76 is W, X77 is V, X78 is P and X79 is S,
the polypeptide of sequence SEQ ID No166 which corresponds to the sequence SEQ ID No151 in which X1 is D, X2 is A, X3 is Q, X4 is F, X5 is V, X6 is Q, X7 is P, X9 is T, X10 is G, X11 is G, X12 is S, X13 is S, X15 is H, X16 is V, X17 is G, X18 is A, X20 is L, X21 is L, X23 is L, X24 is L, X25 is M, X26 is A, X27 is M, X29 is V, X30 is G, X31 is Q, X32 is P, X33 is A, X34 is A, X35 is L, X36 is L, X37 is P, X38 is M, X40 is E, X41 is L, X43 is T, X44 is K, X45 is I, X46 is P, X47 is L, X48 is R, X49 is A, X50 is D, X51 is S, X52 is I, X53 is T, X54 is F, X56 is A, X57 is K, X58 is P, X59 is S, X60 is G, X61 is N, X62 is L, X63 is R, X64 is A, X65 is R, X66 is G, X67 is F, X68 is G, X69 is D, X70 is S, X71 is P, X72 is G, X73 is H, X74 is A, X75 is G, X76 is W, X77 is V, X78 is P and X79 is S,
the polypeptide of sequence SEQ ID No167 which corresponds to the sequence SEQ ID No151 in which X1 is Y, X2 is A, X3 is L, X4 is H, X5 is V, X6 is H, X7 is L, X9 is R, X10 is G, X11 is G, X12 is S, X13 is S, X15 is R, X16 is V, X17 is V, X18 is D, X20 is L, X21 is P, X23 is L, X24 is P, X25 is T, X26 is V, X27 is M, X29 is A, X30 is G, X31 is R, X32 is P, X33 is A, X34 is V, X35 is L, X36 is A, X37 is Q, X38 is M, X40 is E, X41 is P, X43 is I, X44 is R, X45 is I, X46 is P, X47 is L, X48 is H, X49 is A, X50 is G, X51 is S, X52 is T, X53 is T, X54 is F, X56 is A, X57 is R, X58 is P, X59 is S, X60 is G, X61 is S, X62 is L, X63 is R, X64 is A, X65 is R, X66 is G, X67 is S, X68 is G, X69 is D, X70 is S, X71 is P, X72 is G, X73 is R, X74 is A, X75 is D, X76 is W, X77 is V, X78 is P and X79 is S,
the polypeptide of sequence SEQ ID No168 which corresponds to the sequence SEQ ID No151 in which X1 is D, X2 is A, X3 is Q, X4 is Y, X5 is V, X6 is R, X7 is L, X9 is D, X10 is G, X11 is V, X12 is S, X13 is S, X15 is H, X16 is A, X17 is R, X18 is A, X20 is L, X21 is L, X23 is L, X24 is P, X25 is T, X26 is E, X27 is M, X29 is V, X30 is G, X31 is Q, X32 is P, X33 is A, X34 is V, X35 is L, X36 is I, X37 is Q, X38 is M, X40 is V, X41 is P, X43 is T, X44 is R, X45 is T, X46 is P, X47 is L, X48 is H, X49 is A, X50 is D, X51 is S, X52 is T, X53 is T, X54 is F, X56 is A, X57 is R, X58 is P, X59 is S, X60 is G, X61 is N, X62 is L, X63 is R, X64 is A, X65 is R, X66 is G, X67 is S, X68 is G, X69 is D, X70 is F, X71 is P, X72 is V, X73 is L, X74 is A, X75 is D, X76 is W, X77 is V, X78 is P and X79 is S,
the polypeptide of sequence SEQ ID No169 which corresponds to the sequence SEQ ID No151 in which X1 is D, X2 is A, X3 is Q, X4 is Y, X5 is V, X6 is R, X7 is L, X9 is N, X10 is S, X11 is V, X12 is T, X13 is S, X15 is L, X16 is A, X17 is R, X18 is A, X20 is L, X21 is P, X23 is L, X24 is P, X25 is T, X26 is G, X27 is I, X29 is V, X30 is G, X31 is Q, X32 is P, X33 is V, X34 is V, X35 is L, X36 is V, X37 is Q, X38 is M, X40 is V, X41 is P, X43 is T, X44 is R, X45 is I, X46 is P, X47 is L, X48 is R, X49 is V, X50 is D, X51 is S, X52 is T, X53 is T, X54 is F, X56 is A, X57 is R, X58 is P, X59 is S, X60 is G, X61 is S, X62 is L, X63 is R, X64 is A, X65 is R, X66 is G, X67 is S, X68 is W, X69 is D, X70 is S, X71 is P, X72 is A, X73 is L, X74 is A, X75 is D, X76 is L, X77 is V, X78 is P and X79 is S,
the polypeptide of sequence SEQ ID No170 which corresponds to the sequence SEQ ID No151 in which X1 is N, X2 is A, X3 is K, X4 is Y, X5 is V, X6 is H, X7 is L, X9 is D, X10 is G, X11 is V, X12 is S, X13 is P, X15 is H, X16 is A, X17 is R, X18 is A, X20 is P, X21 is P, X23 is L, X24 is P, X25 is T, X26 is G, X27 is M, X29 is V, X30 is V, X31 is Q, X32 is P, X33 is A, X34 is V, X35 is L, X36 is A, X37 is K, X38 is M, X40 is V, X41 is P, X43 is T, X44 is R, X45 is I, X46 is P, X47 is L, X48 is R, X49 is A, X50 is D, X51 is L, X52 is T, X53 is T, X54 is F, X56 is A, X57 is R, X58 is P, X59 is S, X60 is D, X61 is N, X62 is L, X63 is R, X64 is A, X65 is R, X66 is G, X67 is S, X68 is G, X69 is D, X70 is S, X71 is P, X72 is A, X73 is P, X74 is A, X75 is D, X76 is W, X77 is V, X78 is P and X79 is S,
the polypeptide of sequence SEQ ID No171 which corresponds to the sequence SEQ ID No151 in which X1 is D, X2 is A, X3 is Q, X4 is Y, X5 is V, X6 is R, X7 is L, X9 is D, X10 is G, X11 is V, X12 is S, X13 is S, X15 is H, X16 is A, X17 is H, X18 is A, X20 is L, X21 is L, X23 is L, X24 is P, X25 is M, X26 is G, X27 is M, X29 is A, X30 is V, X31 is Q, X32 is P, X33 is V, X34 is V, X35 is L, X36 is V, X37 is Q, X38 is m, X40 is V, X41 is P, X43 is T, X44 is K, X45 is I, X46 is P, X47 is L, X48 is R, X49 is A, X50 is D, X51 is S, X52 is T, X53 is T, X54 is F, X56 is A, X57 is K, X58 is P, X59 is S, X60 is G, X61 is N, X62 is L, X63 is R, X64 is A, X65 is R, X66 is G, X67 is S, X68 is G, X69 is D, X70 is F, X71 is P, X72 is A, X73 is L, X74 is A, X75 is D, X76 is W, X77 is V, X78 is P and X79 is S,
the polypeptide of sequence SEQ ID No172 which corresponds to the sequence SEQ ID No151 in which X1 is D, X2 is A, X3 is Q, X4 is C, X5 is V, X6 is R, X7 is L, X9 is D, X10 is G, X11 is G, X12 is S, X13 is S, X15 is H, X16 is A, X17 is E, X18 is A, X20 is P, X21 is L, X23 is L, X24 is P, X25 is M, X26 is G, X27 is M, X29 is V, X30 is G, X31 is Q, X32 is L, X33 is V, X34 is A, X35 is P, X36 is V, X37 is Q, X38 is M, X40 is V, X41 is H, X43 is T, X44 is R, X45 is I, X46 is P, X47 is S, X48 is R, X49 is V, X50 is D, X51 is S, X52 is I, X53 is T, X54 is F, X56 is V, X57 is N, X58 is P, X59 is S, X60 is G, X61 is N, X62 is L, X63 is R, X64 is A, X65 is R, X66 is G, X67 is S, X68 is G, X69 is D, X70 is S, X71 is P, X72 is A, X73 is L, X74 is A, X75 is D, X76 is W, X77 is V, X78 is P and X79 is L,
the polypeptide of sequence SEQ ID No173 which corresponds to the sequence SEQ ID No151 in which X1 is D, X2 is A, X3 is Q, X4 is Y, X5 is V, X6 is H, X7 is P, X9 is D, X10 is G, X11 is A, X12 is S, X13 is S, X15 is R, X16 is A, X17 is H, X18 is A, X20 is L, X21 is L, X23 is P, X24 is P, X25 is M, X26 is G, X27 is T, X29 is A, X30 is V, X31 is Q, X32 is P, X33 is A, X34 is V, X35 is P, X36 is A, X37 is Q, X38 is M, X40 is A, X41 is P, X43 is T, X44 is R, X45 is I, X46 is P, X47 is L, X48 is R, X49 is A, X50 is D, X51 is S, X52 is T, X53 is I, X54 is F, X56 is A, X57 is R, X58 is P, X59 is S, X60 is G, X61 is N, X62 is L, X63 is R, X64 is A, X65 is R, X66 is G, X67 is F, X68 is G, X69 is D, X70 is S, X71 is P, X72 is D, X73 is P, X74 is A, X75 is D, X76 is W, X77 is V, X78 is L and X79 is S,
the polypeptide of sequence SEQ ID No174 which corresponds to the sequence SEQ ID No151 in which X1 is S, X2 is V, X3 is Q, X4 is C, X5 is A, X6 is R, X7 is L, X9 is V, X10 is G, X11 is A, X12 is N, X13 is S, X15 is R, X16 is A, X17 is E, X18 is A, X20 is L, X21 is P, X23 is L, X24 is P, X25 is M, X26 is G, X27 is M, X29 is A, X30 is G, X31 is Q, X32 is P, X33 is A, X34 is A, X35 is L, X36 is R, X37 is Q, X38 is M, X40 is V, X41 is H, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is R, X49 is A, X50 is D, X51 is S, X52 is T, X53 is I, X54 is F, X56 is A, X57 is R, X58 is P, X59 is S, X60 is G, X61 is N, X62 is P, X63 is G, X64 is P, X65 is R, X66 is G, X67 is Y, X68 is G, X69 is G, X70 is S, X71 is R, X72 is A, X73 is H, X74 is A, X75 is D, X76 is W, X77 is V, X78 is P and X79 is S,
the polypeptide of sequence SEQ ID No175 which corresponds to the sequence SEQ ID No151 in which X1 is G, X2 is V, X3 is Q, X4 is C, X5 is T, X6 is R, X7 is L, X9 is V, X10 is G, X11 is A, X12 is N, X13 is S, X15 is R, X16 is A, X17 is E, X18 is A, X20 is L, X21 is P, X23 is L, X24 is P, X25 is M, X26 is G, X27 is M, X29 is A, X30 is G, X31 is Q, X32 is P, X33 is A, X34 is A, X35 is L, X36 is R, X37 is Q, X38 is M, X40 is V, X41 is P, X43 is I, X44 is R, X45 is I, X46 is P, X47 is S, X48 is H, X49 is A, X50 is D, X51 is S, X52 is A, X53 is T, X54 is F, X56 is A, X57 is R, X58 is P, X59 is S, X60 is G, X61 is N, X62 is P, X63 is G, X64 is L, X65 is R, X66 is G, X67 is Y, X68 is G, X69 is D, X70 is S, X71 is R, X72 is A, X73 is H, X74 is A, X75 is D, X76 is W, X77 is V, X78 is P and X79 is S, and
the polypeptide of sequence SEQ ID No176 which corresponds to the sequence SEQ ID No151 in which X1 is S, X2 is V, X3 is R, X4 is C, X5 is A, X6 is H, X7 is L, X9 is V, X10 is G, X11 is A, X12 is S, X13 is S, X15 is R, X16 is A, X17 is E, X18 is A, X20 is L, X21 is P, X23 is L, X24 is P, X25 is M, X26 is G, X27 is M, X29 is A, X30 is D, X31 is Q, X32 is P, X33 is A, X34 is A, X35 is L, X36 is R, X37 is Q, X38 is M, X40 is V, X41 is P, X43 is I, X44 is R, X45 is T, X46 is P, X47 is S, X48 is H, X49 is A, X50 is D, X51 is S, X52 is T, X53 is T, X54 is F, X56 is A, X57 is R, X58 is P, X59 is S, X60 is G, X61 is N, X62 is P, X63 is G, X64 is P, X65 is R, X66 is G, X67 is Y, X68 is G, X69 is G, X70 is S, X71 is P, X72 is A, X73 is H, X74 is A, X75 is D, X76 is W, X77 is V, X78 is P and X79 is Q.
Preferably, the polypeptide F′ is the polypeptide of sequence SEQ ID No.152.
The applicant has also isolated, unexpectedly, from these polypeptides F′, 4 T epitopes of 9 amino acids, that induce an immune response against the hepatitis C virus.
Thus, another subject of the invention consists of an epitope derived from the protein sequence of the polypeptide F′, characterized in that it induces an immune response against the hepatitis C virus and consists of 9 amino acids located between positions 40 and 48 of the hepatitis C virus polyprotein.
The first epitope isolated, which will subsequently be called A9L, is partially included in the polypeptide F′ in the sense that it begins at position 40. It therefore exhibits a shift of two amino acids relative to the polypeptide F′.
According to a particular embodiment, the A9L epitope has one of the sequences SEQ ID No.177 to SEQ ID No.235, preferably one of the sequences SEQ ID No.177, SEQ ID Nos.183 to 186, SEQ ID Nos.188 to 193, SEQ ID No.201, SEQ ID No.202, SEQ ID No.217, SEQ ID No.218, SEQ ID No.227, SEQ ID No.228 and SEQ ID No.235, the epitope of sequence SEQ ID No.177 being particularly preferred.
According to another subject, the invention relates to the second epitope, subsequently called W9L, characterized in that it induces an immune response specific for the hepatitis C virus and consists of 9 amino acids located between positions 43 and 51 of the hepatitis C virus polyprotein.
According to a particular embodiment, the W9L epitope has one of the sequences SEQ ID No.236 to SEQ ID No.283, preferably one of the sequences SEQ ID No.236, SEQ ID No.241, SEQ ID Nos.248-251, SEQ ID No.253, SEQ ID No.255, SEQ ID No.256 and SEQ ID No.259, the epitope of sequence SEQ ID No.236 being particularly preferred.
According to yet another subject, the invention relates to a third epitope, called R9V, characterized in that it induces an immune response against the hepatitis C virus and consists of 9 amino acids located between positions 50 and 58 of the hepatitis C virus poly-protein.
According to a particular embodiment, the R9V epitope has one of the sequences SEQ ID No.284 to SEQ ID No.358, preferably one of the sequences SEQ ID No.284, SEQ ID No.291, SEQ ID Nos.293 to 295 and SEQ ID Nos.299 to 301, the epitope of SEQ ID No.284 being particularly preferred.
According to yet another subject, the invention relates to a fourth epitope, called G9L, characterized in that it induces an immune response against the hepatitis C virus and consists of 9 amino acids between positions 73 and 81 of the hepatitis C virus polyprotein.
According to a particular embodiment, the G9L epitope has one of the sequences SEQ ID No. 359 to SEQ ID No.434, preferably one of the sequences SEQ ID No. 359, SEQ ID Nos.383 to 386, SEQ ID Nos.388 to 393 and SEQ ID Nos.396 to 400, the epitope of sequence SEQ ID No.359 being particularly preferred.
The present invention also relates to the nucleotide sequences encoding any one of the polypeptides F′ as defined by the sequences SEQ ID Nos. 1 to 176, and also to the nucleotide sequences encoding any one of the epitopes as defined by the sequences SEQ ID Nos.177 to 434.
The polypeptides F′ and epitopes of the invention can be obtained by means of the genetic engineering technique, which comprises the steps consisting in:
culturing a microorganism or eukaryotic cells transformed with a nucleotide sequence according to the invention, and
recovering the peptide produced by said microorganism or said eukaryotic cells.
This technique is well known to those skilled in the art. For further details relating thereto, reference may be made to the following work: Recombinant DNA Technology I, Editors Ales Prokop, Raskesh K Bajpai; Annals of the New York Academy of Sciences, Volume 646, 1991.
The polypeptides F′ and epitopes of the invention can also be prepared by conventional peptide syntheses that are well known to those skilled in the art.
The nucleotide sequences according to the invention can be prepared by chemical synthesis and genetic engineering using the techniques well known to those skilled in the art and described, for example, in J. Sambrook et al., Molecular Cloning: A Laboratory Manual, 1989.
The nucleotide sequences of the invention can be inserted into expression vectors in order to prepare the polypeptides F′ and epitopes of the invention.
Thus, another subject of the invention consists of the expression vectors comprising a nucleotide sequence of the invention, and also the means required for its expression.
By way of an expression vector, mention may be made, for example, of plasmids, viral vectors of the vaccinia virus, adenovirus or baculovirus type, or bacterial vectors of the Salmonella, BCG or listeria type.
The expression “means required for the expression of a polypeptide or epitope” is intended to mean any means that makes it possible to obtain the peptide, such as in particular a promoter, a transcription terminator, an origin of replication and preferably a selection marker.
The vectors of the invention can also comprise sequences required for targeting the peptides to specific cellular compartments. An example of targeting may be the targeting to the endoplasmic reticulum obtained using targeting sequences of the type such as the leader sequence derived from the adenoviral E3 protein (Ciernik I. F., et al., The Journal of Immunology, 199, 162, 3915-3925).
The expression vectors of the invention can comprise either a single nucleotide sequence encoding any one of the polypeptides or epitopes of the invention, or at least two nucleotide sequences encoding different epitopes.
The expression “at least two nucleotide sequences encoding different epitopes” is intended to mean either two nucleotide sequences encoding the following epitope combinations: A9L/W9L, A9L/R9V, A9L/G9L, W9L/R9V, W9L/G9L and R9V/G9L, or three nucleotide sequences encoding the following epitope combinations: A9L/W9L/R9V, A9L/W9L/G9L and W9L/R9V/G9L, or four nucleotide sequences encoding the four epitopes A9L/W9L/R9V/G91, it being understood that the order of the nucleotide sequences is of little importance.
When the expression vectors of the invention comprise several nucleotide sequences, said sequences can be directly linked to one another, or else linked via spacers or linkers that typically consist of small neutral molecules such as amino acids or amino acid mimetics that typically have a neutral charge under physiological conditions.
By way of spacers, mention may be made of Ala or Gly residues or other neutral spacers consisting of non-polar amino acids or of neutral polar amino acids.
These spacer amino acids have at least one or two residues, and conventionally from 3 to 6 residues.
A subject of the invention is also the microorganisms and the eukaryotic cells transformed with an expression vector of the invention.
When it is desired to obtain a composition of the invention containing at least two epitopes of the invention, the microorganisms or eukaryotic cells are transformed with an expression vector containing at least two nucleotide sequences, or else they are co-transformed with at least two expression vectors containing a single nucleotide sequence, each vector encoding an epitope of different type.
By way of examples of microorganisms that are suitable for the purposes of the invention, mention may be made of yeasts such as those of the following families: Saccharomyces, Schizosaccharomyces, Kluveromyces, Pichia, Hanseluna, Yarowia, Schwaniomyces and Zygosaccharomyces, Saccharomyces cerevisiae, Saccharomyces carlsbergensis and Kluveromyces lactis being preferred; and bacteria, such as E. coli and those of the following families: Lactobacillus, Lactococcus, Salmonella, Streptococcus, Bacillus and Streptomyces.
By way of examples of eukaryotic cells, mention may be made of cells originating from animals such as mammals, reptiles, insects and equivalent. The preferred eukaryotic cells are cells originating from the Chinese hamster (CHO cells), from monkey (COS and Vero cells), from baby hamster kidney (BHK cells), from pig kidney (PK 15 cells) and from rabbit kidney (RK13 cells), human osteosarcoma cell lines (143 B cells), HeLa human cells lines and human hepatoma cell lines (of the Hep G2 cell type), and also insect cell lines (for example, Spodoptera frugiperda cell lines).
The host cells can be provided in cultures in suspension or in a flask, or in tissue cultures or organ cultures, and equivalent. The host cells can also be transgenic animals.
The invention also relates to antibodies directed against one of the polypeptides F′ or against one of the epitopes of the invention as defined above.
The antibodies according to the invention are either polyclonal antibodies or monoclonal antibodies.
The abovementioned polyclonal antibodies can be obtained by immunizing an animal with at least one antigen of interest, followed by recovery of the desired antibodies in purified form, by taking a serum sample from said animal and separating said antibodies from the other serum constituents, in particular by affinity chromatography on a column to which is attached an antigen specifically recognized by the antibodies, in particular an antigen of interest.
The monoclonal antibodies can be obtained by the hybridoma technique, the general principle of which is recalled hereinafter.
In a first step, an animal, generally a mouse (or cells in culture in the case of in vitro immunizations), is immunized with an antigen of interest, for which the B lymphocytes are capable of producing antibodies against said antigen. These antibody-producing lymphocytes are then fused with “immortal” myeloma cells (murine in the example) to give hybridomas. The cells capable of producing a particular antibody and of multiplying indefinitely are then selected from the heterogeneous mixture of the cells thus obtained. Each hybridoma is multiplied in the form of a clone, each one resulting in the production of a monoclonal antibody whose properties of recognition with respect to the antigen of interest may be tested, for example by ELISA, by one- or two-dimensional immunoblotting, by immunofluorescence, or using a biosensor. The monoclonal antibodies thus selected are subsequently purified, in particular according to the affinity chromatography technique described above.
The polypeptides F′ and epitopes of the invention are particularly useful for inhibition, prevention and treatment of the virus or of the infection of patients carrying the virus, which belong more particularly to genotypes 1b and 3, such that their use for preparing a drug constitutes another subject of the invention. The present invention also relates to a pharmaceutical composition, in particular a vaccine, containing, as active substance, at least one of the polypeptides F′ as defined above, or else at least epitopes as defined above, or else at least one nucleotide sequence as described above, placed under the control of elements required for constitutive and/or inducible expression of said polypeptides or epitopes, or else at least one antibody as defined above, in combination with a pharmaceutically appropriate vehicle.
The expression “elements required for constitutive expression of the polypeptides or epitopes” is intended to mean a promoter ubiquitous or specific for eukaryotic cells.
By way of elements required for inducible expression of the polypeptides or epitopes, mention may be made of the regulatory elements of the E. coli operon for tetracycline resistance (Gossen M. et al., Proc Natl Acad Sci USA, 89: 5547-5551 (1992)).
Of course, those skilled in the art will readily determine the pharmaceutically appropriate vehicle and the amount of polypeptides, epitopes or antibodies to be used according to the constituents of the pharmaceutical composition.
The amount and the nature of the pharmaceutically appropriate vehicle can be readily determined by those skilled in the art. They are chosen according to the pharmaceutical form and the mode of administration desired.
The pharmaceutical compositions of the invention are suitable for oral, sublingual, subcutaneous, intra-muscular, intravenous, topical, local, intratracheal, intranasal, transdermal, rectal, intraocular or intra-auricular administration, it being possible for said active principle to be administered in a unit form of administration.
The unit forms of administration may, for example, be tablets, gelatin capsules, granules, powders, injectable oral solutions or suspensions, transdermal patches, sublingual, buccal, intratracheal, intraocular, intranasal or intra-auricular administration forms, forms of administration by inhalation, topical, transdermal, subcutaneous, intra-muscular or intravenous administration forms, rectal administration forms, or implants. For topical administration, creams, gels, ointments, lotions or eye lotions can be envisioned.
These pharmaceutical forms are prepared according to the usual methods in the fields under consideration.
Said unit forms contain a dosage so as to allow daily administration of 0.001 to 10 mg of active principle per kg of body weight, according to the pharmaceutical form.
There may be particular cases where higher or lower doses are appropriate; such doses do not depart from the context of the invention. According to the usual practice, the dosage appropriate for each patient is determined by the physician according to the method of administration and the weight and response of the patient.
According to another embodiment of the invention, the present invention also relates to a method of treating pathologies associated with the hepatitis C virus, which comprises the administration, to a patient, of an effective dose of a medicinal product of the invention.
Besides a therapeutic application, the invention also has a diagnostic application in the sense that the polypeptides, the nucleotide sequences encoding said polypeptides and the antibodies of the invention can be used as binding partners in said assays.
The polypeptide and the antibodies of the invention can be used in immunoassays, such as the ELISA assay, and the nucleotide sequences can be used in hybridization assays.
Examples of diagnostic methods comprise, without any implied limitation, blots, “sandwich” techniques, competition techniques and PCR detection techniques, in particular those referred to as “real-time”.
The invention also relates to a diagnostic composition for detecting and/or quantifying the hepatitis C virus, comprising at least one of the polypeptides F′ as defined above, at least one of the nucleotide sequences encoding said polypeptides, as defined above, or else at least one antibody as defined above.
Here again, those skilled in the art will readily determine the amount of polypeptides, nucleotide sequences or antibodies to be used according to the diagnostic technique used.
The invention also relates to a method for detecting and/or quantifying the hepatitis C virus in a biological sample taken from an individual who may be infected with said virus, such as plasma, serum or tissue, characterized in that it comprises the steps consisting in:
The methods for detecting and/or quantifying the virus are carried out using conventional techniques well known to those skilled in the art, and, by way of illustration, mention may be made of blots, “sandwich” techniques, competition techniques and PCR detection techniques, in particular those referred to as “real-time”.
The invention also relates to the use of the compositions of the invention, for the in vitro diagnosis of the hepatitis C virus in a biological sample or specimen.
Finally, the invention relates to the use of the compositions of the invention, for preparing a vaccine composition.
The present invention will be understood more clearly from the following examples given only by way of non-limiting illustration, and also from
A sample of approximately 30 ml of blood was taken, on an anticoagulant (EDTA), from 5 HCV-seropositive patients, and the mononuclear cells were purified on a Ficoll gradient.
Two hundred thousand cells thus purified were incubated in RPMI 1640 medium supplemented with 10% of fetal calf serum in the presence or absence of the polypeptide F′ of sequence SEQ ID No.2 at a concentration of 1 μg/ml, for 24 h.
The cells were then transferred into PVDF ELISpot plates which had been preincubated either with an anti-IFNγ antibody or with an anti-IL-10 antibody according to the supplier's recommendations (Diaclone, Besançon, France), and incubated for a further 24 h at 37° C.
After incubation with a biotinylated antibody specific for IFNγ or for IL-10, followed by streptavidin-coupled alkaline phosphatase, the IFNγ-producing or IL-10-producing cells were revealed after degradation of the substrate (NBT/BCIP).
The blue-colored spots corresponding to the cytokine-producing cells were then counted using an automated system (Zeiss microscope, KS-Elispot program).
The results are given in
This figure clearly shows that the polypeptides of the invention induce an immune response through the production of IL 10, with or without production of IFN gamma.
In this example, the procedure of Example 1 was repeated, the only difference being that the cells from three patients (Pt 5, Pt 4 and Pt 6) were directly incubated in the presence of the A9L (SEQ ID No.177), W9L (SEQ ID No.234), R9V (SEQ ID No.281) and G9L (SEQ ID No.355) epitopes, in the ELISpot plates for 48 h.
The results are given in
Here again, this figure clearly shows that the epitopes of the invention induce an immune response through the production of IL 10, with or without production of IFN gamma.
| Number | Date | Country | Kind |
|---|---|---|---|
| 03/00094 | Jan 2003 | FR | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/FR03/03922 | 12/29/2003 | WO | 7/5/2005 |
