Immunodominant human T-cell epitopes of hepatitis C virus

Abstract

The present invention relates to a polypeptide of about 8 to about 100 amino acids comprising or consisting of at least 8 contiguous amino acids selected from the core, and/or the E1, and/or E2, and/or the NS3 regions of the HCV polyprotein, with said contiguous amino acids containing a T-ell stimulating epitope.

1 . Use of a polypeptide of about 8 to about 100 amino acids for the preparation of an HCV immunogenic composition, with said polypeptide comprising or consisting of at least 8 contiguous amino acids selected from the region comprised between amino acids 73 to 176 in the core region, or between amino acids 192 to 234 and 243 to 392 of the E1 region, or between amino acids 397 and 428 and amino acids 571 to 638 in the E2 region, or between amino acids 1188 and 1463 of the NS3 region of HCV, and with said contiguous amino acids containing a T cell-stimulating epitope.  
     
     
         2 . Use of a polypeptide according to  claim 1  for the preparation of an HCV immunogenic composition, with said polypeptide comprising or consisting of about 8 to about 104 contiguous amino acids selected from the region comprised between amino acids 73 to 176, more particularly comprising or consisting of about 8 to about 68 contiguous amino acids selected from the region between amino acids 109 to 176 in the core region of HCV characterized by the following sequence: 
 NH 2 -GX 1 X 2 WX 3 X 4  PGX 5 PWPLYX 6 NX 7 GX 8 C-X 9 AGWLLSPRGSRPX 10 GX 11 X 12 DPRX 13 X 14 SRMISGX 15 VIDTX 17 TCGX 18 ADLX 19 X 20 YIPX 21 X 22 GX 23 PX 24 GGX 25 X 26 X 27 X 28 LX 29 HGVRX 30 X 31 X 32 DGX 33 NX 34 X 35 TGNX 36 PGCSFSI-COOH  
 (SEQ ID NO 58, spanning positions 73 to 176),  
 wherein X 1  represents R or K, X 2  represents A, S or T. X 3  represents A or G, X 4  represents Q, K or R, X 5  represents Y or H, X 6  represents G or A, X 7 represents E or K, X 8  represents C, M or L, X 9  represents W or L, X 10  represents S, N, T, D or H, X 11  represents P or Q, X 12  represents N or T, X 13 represents R or H, X 14  represents R or K, X 15  represents L or V or F, X 16  represents K or R, X 17  represents L or I, X 18  represents F or L, X 19  represents M or I, X 20  represents G or E, X 21  represents L or V or I, X 22  represents V or L, X 23  represents A or G, X 24  represents L, V, or I, X 25  represents A or V, X 26  represents A or S, X 27  represents R or A, X 28  represents A or T or E, X 29  represents A or E, X 30  represents V or A or L, X 31  represents L or V or I, X 32  represents E or G. X 33  represents V or I, and X 34  represents F or Y, X 35  represents A or P, X 36  represents L or I, and,  
 NH 2 -X 11 X 12 DPRX 13 X 14 SRNX 15 GX 16 VIDTX 17 TCGX 18 ADLX 19 X 20 YIPX 21 X 22 GX 23 PX 24 GGX 25 X 26 X 27 X 28 LX 29 HGVRX 30 X 31 X 32 DGX 33 NX 34 X 35 TGNX 36 PGCSFSI-COOH  
 (SEQ ID NO 48, spanning positions 109 to 176), and with said contiguous amino acids containing a T-cell stimulating epitope.  
 
     
     
         3 . Use of a polypeptide according to  claim 1  for the preparation of an HCV immunogenic composition, with said polypeptide comprising or consisting of at least about 8 contiguous amino acids selected from the region comprised between amino acids 192 to 234 and 243 to 392 of HCV, more particularly selected from the region comprised between amino acids 192 and 234 and 243 to 383 in the El region of HCV characterized by the following sequences: 
 NH 2 -YQVRNSTGLYHVTNDCPNSSIVYEAHDAILHTPGCVCVREGN (SEQ ID NO 164, spanning positions 192 to 234), and, TPTVATTRDGKLPATQLRRHIDLLVGSATLCSALYVGDLCGSVQLFTFSPRRHWTTQGCNCS IYPGHITGHRMAWDMMMNWSPTAALVMAQLLRIPQAILDMIAGAHwGVLAGIAYFSMVGNWA KVLVVLLLFAGVDAETIVSGGQA-COOH (SEQ ID NO 104, spanning positions 243 to 392)  
 or any variant to this sequence derived from another type of HCV as depicted in FIG. 4, and with said contiguous amino acids containing a T-cell stimulating epitope.  
 
     
     
         4 . Use of a polypeptide according to  claim 1  for the preparation of an HCV immunogenic composition, with said polypeptide comprising or consisting of about 8 to about 32 contiguous amino acids selected from the regions between amino acids 397 to 428 in the E2 region, or comprising or consisting of at least 8 to about 68 contiguous amino acids selected from the region between amino acids 571 to 638 in the E2 region of HCV characterized by the following sequences: 
 NH 2 -X 37 X 38 x 39 X 40 X 41 X 42 X 43 X 44 X 45 GX 46 X 47 QX 48 X 49 X 50 LX 51 NX 54 NGSWHX 52 NX 53 TALN-COOH (SEQ ID NO 49, spanning positions 397 to 428), and,  
 NH 2 -IX 55 X 56 X 57 X 58 NX 59 X 60 Z 1 Z 2 LX 61 CPTDCFRKX 62 PX 63 X 64 TYX 65 X 66 CGX 67 GPX 68 X 69 TPRCX 70 X 71 DYPYRLWHYPCTX 72 NX 73 X 74 X 75 FKX 76 RMX 77 VGGVEH-COOH (SEQ ID NO 108, spanning positions 571 to 638),  
 wherein X 3 , represents S, A, Q, L, N, Y, R, Y or H, X 38  represents G, S, T, A or R, X 39 , represents F, I, L, or V; X 40  represents V, A, or T; X 41 represents S, D or G; X 42  represents L, I, W, F, or M; X 43  represents L, I or F, X 44  represents A, T, D or S; X 45  represents P, Q, S, R, L, I or T; X 46  represents A, P, or S; X 47  represents K, S, Q, A, or R; X 48  represents N, K, D, or R; X 49  represents V, I, or L; X 50  represents Q, S or Y; X 51  represents I or V; X 52  represents L or I; X 53  represents S or R; and X 54  represents T or S; X 55  represents G or R; X 56  represents G, A, or K, X 57  represents A, V, G, S, or D; X 58  represents G, F, or Y; X 59  represents N, H, R, L, A, or S; X 60  represents T or S; Z 1  represents represents M or I; Z 2  represents D; X 61  represents H, L, V, T, or I; X 62  represents H or Y; X 63  represents D or E; X 64  represents A or T; X 65  represents S, T, I, or L; X 66  represents R or K; X 67  represents S or A, X 68  represents W or L; X 69  represents I or L; X 70  represents L, M or I, X 71  represents V or I; X 72  represents I, V, F, or L; X 73  represents Y or F; X 74  represents T, S or A; X 75  represents I or V; X 76  represents I, V or A, X 77  represents Y or F, and with said contiguous amino acids containing a T cell stimulating epitope.  
 
     
     
         5 . Use of a polypeptide according to  claim 1  for the preparation of an HCV immunogenic composition, with said polypeptide comprising or consisting of at least about 8 contiguous amino acids selected from the region comprised between amino acid positions 1188 to 1463 of the NS3 region of HCV characterized by the following sequence: 
 NH 2 -GVAKAVDFVPVESMETTMRSPVFTDNSSPPAVPQTFQVA HLEAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGVDPNIRTGVRTITTG APITYSTYGKFLADGGCSGGAYDIIIICDECESIDSTSILGIGTVLDQAETAGARLVVLATAT PPGSVTVPHPNIEEVALSSTGEIPFYGKAIPIEVIKGGRHLIFCHSKKKCDELAAKLSGFGI NAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTGDFDSVIDCNTCVTQTVDFS-COOH (SEQ ID NO 57), or any variant of said sequence as can be deduced from FIG. 6, and with said contiguous amino acids containing a T cell stimulating epitope.  
 
     
     
         6 . Use of a polypeptide according to  claim 2 , for the preparation of an HCV immunogenic composition, with said polypeptide comprising or consisting of about 8 to about 20 contiguous amino acids selected from the region comprised between amino acid positions 157 to 0.176 of the core region of HCV: 
 NH 2 -X 30 X 31 X 32 DGX 33 NX 34 X 35 TGWX 36 PGCSFSI-COOH (SEQ ID NO 51),    and more particularly selected from VTLEDGVNYATGNLPGCSFSI (SEQ ID NO 13=peptide CORE 27) or VLEDIVNYATGNLPGCSFSI (SEQ ID NO 73), with said peptides being preferentially chosen from the following list of peptides:    NH 2 -GX 33 NX 34 X 35 TGNX 36 -COOH (SEQ ID NO 74),    NH 2 -X 33 NX 34 X 35 TGNX 36 -COOH (SEQ ID NO 75),    NH 2 -NX 36 PGCSFSI-COOH (SEQ ID NO 76) and    NH 2 -X 36 PGCSFSI-COOH (SEQ ID NO 77), and more particularly GVNYATGNL (SEQ ID NO 78), GVNYATGNL (SEQ ID NO 79), NLPGCSFSI (SEQ ID NO 80) and LPGCSFSI (SEQ ID NO 81), and with said contiguous amino acids containing a T cell stimulating epitope.    
     
     
         7 . Use of a polypeptide according to  claim 2  for-the preparation of an HCV immunogenic composition, with said polypeptide comprising or consisting of about 8 to about 20 contiguous amino acids selected from the region comprised between amino acid positions 145 to 164 of the core region of HCV: 
 NH 2 -GGX 25 X 26 X 27 X 28 LX 29 HGVRX 30 X 31 X 32 DGX 33 NX 34 -COOH (SEQ ID NO 52), and more particularly selected from GGAARALAHFVRLEDGVNY (SEQ ID NO 12=peptide CORE 25) or GGVAARALAHGVRVLEDGVNY (SEQ ID NO 118), with said peptides being particularly chosen from the following list of peptides:  
 NH 2 -X 28 LX 29 HGVRX 30 X 31 -COOH (SEQ ID NO 82), NH 2 -LX 29 HGVRX 30 X 31 -COOH (SEQ ID NO 83), NH 2 -GVRX 30 X 31 X 32 DGX 33 -COOH (SEQ ID NO 84),  
 NH 2 -VRX 30 X 31 X 32 DGX 33 -COOH (SEQ ID NO 85),  
 NH 2 -RX 30 X 31 X 32 DGX 33 NX 34 -COOH (SEQ ID NO 86), and  
 NH 2 -X 30 X 31 X 32 DGX 33 NX 34 -COOH (SEQ ID NO 87), and more particularly: ALAHGVRVL (SEQ ID NO 88), LAHGVRVL (SEQ ID NO 89), VRVLEDGV (SEQ ID NO 90), RVLEDGV (SEQ ID NO 91), VLEDGVNY (SEQ ID NO 92), and LEDGVNY (SEQ ID NO 93), and with said contiguous amino acids containing a T cell stimulating epitope.  
 
     
     
         8 . Use of a polypeptide according to  claim 2  for the preparation of an HCV immunogenic composition, with said polypeptide comprising or consisting of about 8 to about 20 contiguous amino acids selected from the region comprised between amino acid positions 133 to 152 of the core region of HCV: 
 NH 2 -LX 19 X 20 YIPX 21 X 22 GX 23 PX 24 GGX 25 X 26 X 27 X 28 LX 29 -COOH (SEQ ID NO 53), and more particularly selected from LMGYIPLVGAPLGGAARALA (SEQ ID NO 11=peptide CORE 23), with said peptides being preferentially chosen from the following list of peptides:  
 NH 2 -X 19 X 20 YIPX 21 X 22 GX 23 PX 24 GGX 25 -COOH (SEQ ID NO 63),  
 NH 2 -YIPX 21 X 22 GX 23 PX 24 -COOH (SEQ ID NO 64),  
 NH 2 -YIPX 21 X 22 GX 23 PX 24 -COOH (SEQ ID NO 65),  
 NH 2 -X 21 X 22 GX 23 PX 24 GGX 25 -COOH (SEQ ID NO 0.66), and  
 NH 2 -X 22 GX 23 PX 24 GGX 25 -COOH (SEQ ID NO 68), more particularly 
 LMGYIPLV (SEQ ID NO 69), MGYIPLV (SEQ ID NO 70), YIPLVGAPL (SEQ ID NO 71), IPLVGAPL (SEQ ID NO 72), LVGAPLGGA (SEQ ID NO 94), and VGAPLGGA (SEQ ID NO 95), and with said contiguous amino acids containing a T cell stimulating epitope.  
 
 
     
     
         9 . Use of a polypeptide according to  claim 2  for the preparation of an HCV immunogenic composition, with said polypeptide comprising or consisting of about 8 to about 20 contiguous amino acids selected from the region comprised between amino acid positions 109 to 128 of the core region of HCV: 
 NH 2 -X 11 X 12 DPRX 13 X 14 SRNX 15 GX 16 VIDTX 17 TC-COOH (SEQ ID NO 54),  
 and more particularly selected from PTDPRRRSRNLGKVIDTLTC (SEQ ID NO 9=peptide CORE 19), with said peptides being particularly chosen from the following peptides:  
 NH 2 -NX 15 GX 16 VIDTX 17 -COOH (SEQ ID NO 96) or  
 NH 2 -X 15 GX 16 VIDTX 17 -COOH (SEQ ID NO 97). More particularly NLGKVIDTL (SEQ ID NO 98) and LGKVIDTL (SEQ ID NO 117), and with said contiguous amino acids containing a T cell stimulating epitope.  
 
     
     
         10 . Use of a polypeptide according to  claim 2  for the preparation of an HCV immunogenic composition, with said polypeptide comprising or consisting of at least 8 to about 20 contiguous amino acids selected from the region comprised between amino acid positions 73 to 92 of the core region of HCV: 
 NH 2 -GX 1 X 2 WX 3 X 4 PGX 5 PWPLYX 6 NX 7 GX 8 G-COOH (SEQ ID NO 99),  
 and more particularly selected from GRTWAQPGYPWPLYGNEGCG (SEQ ID NO 6=peptide CORE 13), with said peptides being preferably selected from:  
 NH 2 -X 2 WX 3 X 4 PGX 5 PW-COOH (SEQ ID NO 100) and NH 2 -WX 3 X 4 PGX 5 PW-COOH (SEQ ID NO 101), such as the peptides: TWAQPGYPW (SEQ ID NO 102) and WAQPGYPW (SEQ ID NO 103), and with said contiguous amino acids containing a T cell stimulating epitope.  
 
     
     
         11 . Use of a polypeptide according to  claim 2  for the preparation of an HCV immunogenic composition, with said polypeptide comprising or consisting of at least 8 to about 44 contiguous amino acids selected from the region comprised between amino acid positions 133 to 176 of the core region of HCV: 
 N2-LX 19 X 20 YIPX 21 X 22 X 23  PX 24 X 25 X 26 X 27 X 28 X 29 HGVRX 30 X 31 X 32 DGX 33 NX 34 X 35 TGNX 36 PGCSFSI-COOH (SEQ ID NO 50), and more particularly selected from peptide LMGYIPLVGAPLGGAARAHGVRVLEDGVNYAT GNLPGCSFSI (SEQ ID NO 67), and with said contiguous amino acids containing a T-cell stimulating epitope.  
 
     
     
         12 . Use of a polypeptide according to  claim 3  for the preparation of an HCV immunogenic composition, with said polypeptide comprising or consisting of at least 8 to about 68 contiguous amino acids selected from the region comprised between amino acid positionsacids 193 to 234 and 243 to 260 in the E1 region of ECV characterized by the following sequence: 
 QVRNSTGLYHVTNDCPNSSIVYEAHDAILHTPGCVPCVREGN (SEQ ID NO 165, spanning positions 193 to 234), and,  
 TPTVATTRDGKLPATQLR (SEQ ID NO 105, spanning positions 243 to 260)  
 with said peptides being particularly chosen from:  
 QVRNSTGLYHVTNDCPNSSI (SEQ ID NO 16),  
 NDCPNSSIVYEAEDAILHTP (SEQ ID NO 17),  
 HDAILHTPGCVPCVREGNVS (SEQ ID NO 18),  
 CVREGNVSRCWVAMTPTVAT (SEQ ID NO 19), and,  
 AMTPTVATRDGKLPPATQLRR (SEQ ID NO 20), or any variant to this sequence derived from another type of HCV as depicted in FIG. 4, and with said contiguous amino acids containing a T cell stimulating epitope.  
 
     
     
         13 . Use of a polypeptide according to  claim 3  for the preparation of an HCV immunogenic composition, with said polypeptide comprising or consisting of at least 8 to about 80 contiguous amino acids selected from the region comprised between amino acids 253 to 332 in the El region of HCV characterized by the following sequence: 
 NH 2 -LPATQLRRHIDLLVGSATLCSALYVGDLCGSVQLFTFSPRRH WTTQGCNCSIYPGHITGHRMAWDMMMNWSPTAAL-COOH (SEQ ID NO 106), or any variant to this sequence derived from another type of HCV as depicted in FIG. 4, with said peptides being particularly chosen from  
 LPATQLRRHIDLLVGSATLC (SEQ ID NO 21),  
 LVGSATLCSALYVGDLCGSV (SEQ ID NO 22),  
 QLFTFSPRRHWTrQGCNCSI (SEQ ID NO 23),  
 TQGCNCSIYPGHITGHRMAW (SEQ ID NO 24), and,  
 ITGHRMAWDMMMNWSPTAAL (SEQ ID NO 25), and with said contiguous amino acids containing a T cell stimulating epitope.  
 
     
     
         14 . Use of a polypeptide according to  claim 3  for the preparation of an HCV immunogenic composition, with said polypeptide comprising or consisting of at least 8 to about 68 contiguous amino acids selected from the region comprised between amino acids 325 to 392 in the E1 region of HCV characterized by the following sequence: 
 NH 2 -MNWSPTAALVMAQLLRIPQAILDMIAGAHWGVLAGIAYFSMVGNW AKVLVVLLLFAGVDAETIVSGGQA-COOH (SEQ ID NO 107), or any variant to this sequence derived from another type of HCV as depicted in FIG. 4, with said peptides being particularly chosen from  
 NWSPTAALVMAQLLRIPQAI (SEQ ID NO 26),  
 LLRIPQAILDMIAGAHWGVL (SEQ ID NO 27),  
 AGAHWGVLAGIAYFSMVGNW (SEQ ID NO 28), and,  
 VVLLLFAGVDAETIVSGGQA (SEQ ID NO 29), and with said contiguous amino acids containing a T cell stimulating epitope.  
 
     
     
         15 . Use of a polypeptide according to  claim 4  for the preparation of an HCV immunogenic composition, with said polypeptide comprising or consisting of about 8 to about 20 contiguous amino acids selected from the region comprised between amino acid positions 397 to 416 of the E2 region of HCV: 
 NH 2 -X 37 X 38 X 39 X 40 CX 41 X 42 X 43 X 44 X 45 GX 46 X 47 QX 48 X 49 X 50 LX 51 NX 54 -COOH (SEQ ID NO 55) and more particularly selected from SGLVSLFTPGAKQNIQLINT (SEQ ID NO 46 or peptide NS1-7*), and with said contiguous amino acids containing a T cell stimulating epitope.  
 
     
     
         16 . Use of a polypeptide according to  claim 4  for the preparation of an HCV immunogenic composition, with said polypeptide comprising or consisting of about 8 to about 20 contiguous amino acids selected from the region comprised between amino acid positions 409 to 428 of the E2 region of HCV: 
 NH 2 -QX 48 X 49 X 50 LX 51 NX 54 NGSWHX 52 NX 53 TALN-COOH (SEQ ID NO 56), and more particularly selected from QNIQLINTNGSWHINSTALN (SEQ ID NO 47 or peptide NS1-5′), with said peptides being particularly chosen from  
 NH 2 -X 50 LX 51 NX 54 NGSW-COOH (SEQ ID NO 109),  
 NH 2 -LX 51 NX 54 NGSW-COOH (SEQ ID NO 110),  
 NH 2 -SWHX 52 NX 53 TAL-COOH (SEQ ID NO 111), and NH 2 -SWHX 52 NX 53 TAL-COOH (SEQ ID NO 112), more particularly QLINTNGSW (SEQ ID NO 113), LINTNGSW (SEQ ID NO 114), SWHINSTAL (SEQ ID NO 115) and WHINSTAL (SEQ ID NO 116), and with said contiguous amino acids containing a T cell stimulating epitope.  
 
     
     
         17 . Use of a polypeptide according to  claim 4  for the preparation of an HCV immunogenic composition, with said polypeptide comprising or consisting of at least 8 to about 20 contiguous amino acids selected from the region comprised between amino acid positions 571 to 638 of the E2 region of HCV: 
 NH 2 -IX 55 X 56 X 57 X 58 NX 59 X 60 Z 1 Z 2 LX 61 CPTDCFRKX 62 PX 63 X 64 TYX 65 X 66 CGX 67 GPX 68 X 69  TPRCX 70 CX 71 DYPRLWHYPCTX 72 NX 73 X 74 X 75 FKX 76 RMX 77 VCGVEH-COOH (SEQ ID NO 108), more preferably chosen from the following list of peptides:  
 X 60 Z 1 Z 2 LX 63 CPTDCF (SEQ ID NO 119),  
 FRKX 62 PX 63 X 64 TY (SEQ ID NO 120),  
 X 68 X 69 -TPRCX 70 CX 71  (SEQ ID NO 121),  
 X 70 X 71 DYPYRL (SEQ ID NO 122),  
 X 71 DYPYRLW (SEQ ID NO 123),  
 YPYRLWHY (SEQ ID NO 124),  
 LWHYPCTX 72  (SEQ ID NO 125),  
 X 72 NX 72 X 74 X 75 FKX 76  (SEQ ID NO 126),  
 X 73 X 74 X 75 FKX 76 RM (SEQ ID NO 127),  
 X 75 FKX 76 RMX 77 V (SEQ ID NO 128),  
 X 76 RMX 77 VGGV (SEQ ID NO 129),  
 IX 55 X 56 X 57 X 58 NX 59 X 60 Z 1 Z 2 LX 61 CPTDCFRKX 62 P (SEQ ID NO 130),  
 TDCFRKX 62 PX 63 X 64 TYX 65  X 66 CGX 67 GPX 68  (SEQ ID NO 131),  
 X 65 X 66 CGX 67 GPX 68 X 69 TPRCX 70 X 71 DYPYR (SEQ ID NO 132),  
 CX 70 X 71 DYPYRLWHYPCTX 72 NX 73 X 74 X 75 (SEQ ID NO 133),  
 PCTX 72 NX 73 X 74 X 75 FKX 76 RMX 77 VGGVEH (SEQ ID NO 134),  
 and with said contiguous amino acids containing a T-cell stimulating epitope.  
 
     
     
         18 . Use of a polypeptide according to claim S, for the preparation of an HCV immunogenic composition, with said polypeptide comprising or consisting of at least 8 contiguous amino acids selected from the region comprised between amino acid positions 1188 to 1463 of the NS3 region of HCV and with said peptides being selected from the following list of peptides: 
 VAKAVDFV (SEQ ID NO 135), VAKAVDFI (SEQ ID NO 136), VESMETTM=(SEQ ID NO 137), AVPQTFQV (SEQ ID NO 138), YAAQGYKV (SEQ ID NO 139), VLVLNPSVA (SEQ ID NO 140), YMSKAHGV (SEQ ID NO 141), IRTGVRTI (SEQ ID NO 142), YSTYGKFL (SEQ ID NO 143), ILGIGTVL (SEQ ID NO 144), VTVPHPNI (SEQ ID NO 145), IPFYGKAI (SEQ ID NO 146), FYGKAIPI (SEQ ID NO 147), VIKGGRHL (SEQ ID NO 148), IKGGRHLI (SEQ ID NO 149), FCHSKKKC (SEQ ID NO 150), CDELAAKL (SEQ ID NO 151), LAAKLSGFG (SEQ ID NO 152), SGFGINAV (SEQ ID NO 153), FGINAVAY (SEQ ID NO 154), YRGLDVSV (SEQ ID NO 155), VIPTSGDV (SEQ ID NO 156), IPTSGDVV (SEQ ID NO 157), VVVATDAL (SEQ ID NO 158), VVATDALM (SEQ ID NO 159), MTGFTGDF (SEQ ID NO 160), FTGDFDSV (SEQ ID NO 161), KLVALGINAV (SEQ ID NO 166), VIDCNTCV (SEQ ID NO 162), or any variant of said sequence as can be deduced from FIG. 6, and with said contiguous amino acids containing a T-cell stimulating epitope.    
     
     
         19 . Use of a polypeptide according to any of  claims 1  to  18  wherein said T cell stimulating epitope is a T cell helper epitope.  
     
     
         20 . Use of a polypeptide according to any of  claims 1  to  18  wherein said T cell stimulating epitope is a CTL epitope.  
     
     
         21 . Use of a polypeptide according to any of  claims 1  to  20  for incorporation into a prophylactic vaccine composition.  
     
     
         22 . Use of a polypeptide according to any of  claims 1  to  20  for incorporation into a therapeutic vaccine composition.  
     
     
         23 . A polypeptide comprising in its amino acid sequence multiple repeats, combinations or mimiotopes of any of the contiguous amino acid sequences selected to contain T cell stimulating epitopes as defined in any of  claims 1  to  22 .  
     
     
         24 . A polypeptide according to any of  claims 1  to  23 , with said polypeptide being a recombinant polypeptide expressed by means of an expression vector comprising a nucleic acid insert encoding a polypeptide according to any of  claims 1  to  23 .  
     
     
         25 . A polypeptide according to any of  claims 1  to  24  which is operably linked to a pathogen related immunogen, such as the HCV envelope proteins E1 and E2, or the HCV NS3, NS4 or NS5 immunogens, or a HCV peptide containing a B cell stimulating epitope.  
     
     
         26 . A peptide consisting of or comprised in the sequence of any of the following peptides, with said peptides containing a T cell epitope: 
 NH 2 -X 30 X 31 X 32 DGX 33 NX 34 X 35 TGNX 36 PGCSFSI-COOH (SEQ ID NO 51),    VLEDGVNYATGNLPGCSFSI (SEQ ID NO 13=peptide CORE 27),    VLEDIVNYATGNLPGCSFSI (SEQ ID NO 73),    NH 2 -GX 33 NX 34 X 35 TGNX 36 -COOH (SEQ ID NO 74),    NH 2 -X 33 NX 34 X 3 STGNX 36 -COOH (SEQ ID NO 75),    NH 2 -NX 36 PGCSFSI-COOH (SEQ ID NO 76),    NH 2 -X 36 PGCSFSI-COOH (SEQ ID NO 77),    GVNYATGNL (SEQ ID NO 78), GVNYATGNL (SEQ ID NO 79),    NLPGCSFSI (SEQ ID NO 80), LPGCSFSI (SEQ ID NO 81),    NH 2 -GGX 25 X 26 X 27 X 28 X 29 HGVRX 30  X 31 X 32 DGX 33 NX 34 -COOH (SEQ ID NO 52),    GGAARALAHGVRVLEDGVNY (SEQ ID NO 12 peptide CORE 25),    GGVAARALAHGVRVLEDGVNY (SEQ ID NO 118),    NH 2 -X 28 LX 29 HGVRX 30 X 31 -COOH (SEQ ID NO 82),    NH 2 -LX 29 HGVRX 30 X 31 -COOH (SEQ ID NO 83),    NH 2 -GVRX 30 X 31 X 32 DGX 33 -COOH (SEQ ID NO 6i),    NH 2 -VRX 30 X 31 X 32 DGX 33 -COOH (SEQ ID NO 85),    NH 2 -RX 30 X 31 X 32 DGX 33 NX 34 -COOH (SEQ ID NO 86),    NH 2 -X 30 X 31 X 32 DGX 33 NX 34 -COOH (SEQ ID NO 87),    ALAHGVRVL (SEQ ID NO 88), LAHGVRVL (SEQ ID NO 89),    VRVLEDGV (SEQ ID NO 90), RVLEDGV (SEQ ID NO 91), VLEDGVNY (SEQ ID NO 92), LEDGVNY (SEQ ID NO 93),    NH 2 -LX 19 X 20 YIPX 21 X 22 GX 23 PX 24 GGX 25 X 26 X 27 X 28 LX 29 -COOH (SEQ ID NO 53),    LMGYIPLVGAPLGGAARALA (SEQ ID NO 11=peptide CORE 23),    NH 2 -LX 19 X 20 YIPX 21 X 22 GX 23 PX 24 GGX 25 -COOH (SEQ ID NO 62),    NH 2 -X 19 X 20 YIPX 21 X 22 GX 23 PX 24 GGX 25 -COOH (SEQ ID NO 63)    NH 2 -YIPX 21 X 22 GX 23 PX 24 -COOH (SEQ ID NO 64),    NH 2 -IPX 21 X 22 GX 23 PX 24 -COOH (SEQ ID NO 65),    NH 2 -X 21 X 22 GX 23 PX 24 GGX 25 -COOH (SEQ ID NO 66),    NH 2 -X 22 GX 23 PX 24 GGX 25 -COOH (SEQ ID NO 68),    LMGYIPLV (SEQ ID NO 69), MGYIPLV (SEQ ID NO 70),    YIPLVGAPL (SEQ ID NO 71), IPLVGAPL (SEQ ID NO 72),    LVGAPLGGA (SEQ ID NO 94), VGAPLGGA (SEQ ID NO 95),    NH 2 -x 11 X 12 DPRX 13 X 14 SRNX 15 GX 16 VIDTX 17 TC-COOH (SEQ ID NO 54),    PTDPRRRSRNLGKVIDTLTC (SEQ ID NO 9=peptide CORE 19),    NH 2 -NX 15 GX 16 VIDTX 17 -COOH (SEQ ID NO 96),    NH 2 -X 15 GX 16 VIDTX 17 -COOH (SEQ ID NO 97),    NLGKVIDTL (SEQ ID NO 98), LGKVIDTL (SEQ ID NO 117),    NH 2 -GX 1 X 2 WX 3 X 4 PGX 5 PWPLYX 6 NX 7 GX 8 G-COOH (SEQ ID NO 99),    GRTWAQPGYPWPLYGNEGCG (SEQ ID NO 6=peptide CORE 13),    NH 2 -X 2 WX 3 X 4 PGX 5 PW-COOH (SEQ ID NO 100),    NH 2 -WX 3 X 4 PGX 5 PW-COOH (SEQ ID NO 101),    TWAQPGYPW (SEQ ID NO 102), WAQPGYPW (SEQ ID NO 103),    QVRNSTGLYHVTNDCPNSSI (SEQ ID NO 16),    NDCPNSSIVYEAHDAILHTP (SEQ ID NO 17),    HDAILHTPGCVPCVREGNVS (SEQ ID NO 18),    CVREGNVSRCWVAMTPTVAT (SEQ ID NO 19),    AMTPTVATRDGKLPPATQLRR (SEQ ID NO 20),    LPATQLPRHIDLLVGSATLC (SEQ ID NO 21),    LVGSATLCSALYVGDLCGSV (SEQ ID NO 22),    QLFTFSPRQGCNCSI (SEQ ID NO 23),    TQGCNCSIYPGHITGHRMAW (SEQ ID NO 24),    ITGHRMAWDMMMNWSPTAAL (SEQ ID NO 25),    NWSPTAALVMAQLLRIPQAI (SEQ ID NO 26),    LLRIPQAILDMIAGAHWGVL (SEQ ID NO 27),    AGAHWGVLAGIAYFSMVGNW (SEQ ID NO 28),    VVLLLFAGVDAETIVSGGQA (SEQ ID NO 29),    NH 2 -X 37 X 38 X 39 X 40 X 41 X 42 X 43 X 44 X 45 GX 46 X 47 QX 48 X 49 X 50 LX 51 NX 54 -COOH (SEQ ID NO 55),    SGLVSLFTPGAKQNIQLINT (SEQ ID NO 46),    NH 2 -QX 48 X 49 X 50 LX 51 NX 54 NGSWHX 52 NX 53 TA-COOH (SEQ ID NO 56),    NH 2 -X 50 LX 51 NX 54 NGSW-COOH (SEQ ID NO 109),    NH 2 -LX 51 NX 54 NGSW-COOH (SEQ ID NO 110),    NH 2 -COOH (SEQ ID NO 111),    NH 2 -SWHX 52 NX 53 TAL-COOH (SEQ ID NO 112), QLINTNGSW (SEQ ID NO 113),    LINTNGSW (SEQ ID NO 114), SWHINSTAL (SEQ ID NO 115), WHINSTAL (SEQ ID NO 116),    GGAGNNTLHCPTDCFRKHP (SEQ ID NO 41),    TDCFRKXPDATYSRCGSGPW (SEQ ID NO 42),    SRCGSGPWITPRCLVDYPYR (SEQ ID NO 43),    CLVDYPYRLWHYPCTINYTI (SEQ ID NO 44),    PCTINYTIFKIRMYVGGVEH (SEQ ID NO 45),    X 60 Z 1 Z 2 LX 61 CPTDCF (SEQ ID NO 119),    FRKX 62 PX 63 X 64 TY (SEQ ID NO 120),    X 68 X 69 TPRCX 70 X 71  (SEQ ID NO 121),    X 70 X 71 DYPYRL (SEQ ID NO 122),    X 71 DYPYRLW (SEQ ID NO 123),    YPYRLWHY (SEQ ID NO 124),    LWHYPCTX 72  (SEQ ID NO 125),    X 72 NX 73 X 74 X 75 FKX 76  (SEQ ID NO 126),    X 73 X 74 X 75 FKX 76 RM (SEQ ID NO 127),    X 75 FKX 76 RMX 77 V (SEQ ID NO 128),    X 76 RMX 77 VGGV (SEQ ID NO 129),    TDCFRKX 62 PX 63 X 64 TYX 65 X 66 CGX 67 GPX 68  (SEQ ID NO 131),    X 65 X 66 CGX 67 GPX 68 X 69 TPRCX 70 X 71 DYPYR (SEQ ID NO 132)),    CX 70 X 71 DYPYRLWHYPCTX 72 NX 73 X 74 X 75  (SEQ ID NO 133),    PCTX 72 NX 73 X 74 X 75 FKX 76 RMX 77 VGGVEH (SEQ ID NO 134).    VAKAVDFV (SEQ ID NO 135), VAKAVDFI (SEQ ID NO 136), VESMETTM (SEQ ID NO 137), AVPQTFQV (SEQ ID NO 138), YAAQGYKV (SEQ ID NO 139), VLVLNPSVA (SEQ ID NO 140), YMSKAHGV (SEQ ID NO 141), IRTGVRTI (SEQ ID NO 142), YSTYGKFL (SEQ ID NO 143), ILGIGTVL (SEQ ID NO 144), VTVPHPNI (SEQ ID NO 145), IPFYGKAI (SEQ ID NO 146), FYGKAIPI (SEQ ID NO 147), VIKGGRHL (SEQ ID NO 148), IKGGRHLI (SEQ ID NO 149), FCHSKKKC (SEQ ID NO 150), CDELAAKL (SEQ ID NO 151), LAAKLSGFG (SEQ ID NO 152), SGFGINAV (SEQ ID NO 153), FGINAVAY (SEQ ID NO 154), YRGLDVSV (SEQ ID NO 155), VIPTSGDV (SEQ ID NO 156), IPTSGDVV (SEQ ID NO 157), VVVATDAL (SEQ ID NO 158), VVATDALM (SEQ ID NO 159), MTGFTGDF (SEQ ID NO 160), FTGDFDSV (SEQ ID NO 161), VIDCNTCV (SEQ ID NO 162).    
     
     
         27 . An immunogenic composition consisting of or comprising at least one of the peptides or polypeptides according to  claim 26  mixed with a pharmaceutically acceptable excipient.  
     
     
         28 . A vaccine composition according to any of  claim 27 .  
     
     
         29 . A prophylactic vaccine composition according to  claim 28 .  
     
     
         30 . A Therapeutic vaccine composition according to  claim 29 .  
     
     
         31 . A composition according to any of  claims 27  to  30 , with said composition comprising in addition to any of the polypeptides according to  claim 26 , a peptide or polypeptide containing at least one B cell stimulating epitope of HCV, and/or a structural HCV polypeptide, and/or a non-structural HCV polypeptide.  
     
     
         32 . A composition according to any of  claims 27  to  31 , wherein said polypeptide according to  claim 26  is mixed with HBsAg or HBcAg particles, HBV immunogens, HIV immunogens and/or HTLV immunogens.