Polyepitopic protein fragments of the E6 and E7 proteins of HPV, their production and their use particularly in vaccination
AssigneesInstitut National De La Sante Et De La Recherche Medicale (Inserm), Peptide Immune Ligands
InventorsJeannine Choppin, Isabelle Villada, Jean-Gerard Guillet, Francine Connan, Estelle Ferries
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Abstract
Polyepitopic peptides of E6 and E7 proteins of Human Papillomavirus, their production, and methods of treating pathologies in which a polyepitopic peptide of the E6 and E7 protein of Human Papillomavirus is recognized by the cellular immune system.
Claims23
Polyepitopic fragments of the E6 or E7 protein of HPV, characterized in that they comprise a peptide sequence of about 15 to 30 amino acids, this peptide sequence containing amino acid sequences of at least 3 different epitopes binding stably to HLA molecules of identical or different type, when these epitopes are obtained by enzymatic degradation of said peptide sequence, particularly in the proteasome, such that at least 4 HLA molecules of different types bind to these epitopes, these 4 HLA molecules being selected from among those of types A1, A2, A3, A11, A24, A29, B7, B8, B18, B27, B35, B44, B51 and B62.
A polyepitopic fragment comprising SEQ ID NO:
- 8 or SEQ ID NO:
- 10.
A pharmaceutical composition, or vaccine, characterized in that it comprises:
- at least one nucleotide sequence, coding for polyepitopic fragment of the E6 or E7 protein,
- and/or at least one nucleotide sequence coding for a peptide sequence derived from said fragment,
- and/or at least one suitable vector, in association with a physiologically acceptable vehicle.
Epitopes of the E6 protein of HPV selected from the following:
- (19)LPQLCTEL(26) (residues 19 to 26 of SEQ ID NO:
- 2) binding stably to HLA molecules of the B51 type,
- (21)QLCTELQTTI(30) (residues 21 to 30 of SEQ ID NO:
- 2) binding stably to HLA molecules of the A2 type,
- (24)TELQTTIHDI(33) (residues 24 to 33 of SEQ ID NO:
- 2) binding stably to HLA molecules of the A29 or B44 type,
- (33)IILECVYCK(41) (residues 33 to 41 of SEQ ID NO:
- 2) binding stably to HLA molecules of the A11 type,
- (35)LECVYCKQQL(44) (residues 35 to 44 of SEQ ID NO:
- 2) binding stably to HLA molecules of the A29 or B44 type,
- (37)CVYCKQQL(44) (residues 37 to 44 of SEQ ID NO:
- 2) binding stably to HLA molecules of the B8 type,
- (46)RREVYDFAFR(55) (residues 46 to 55 of SEQ ID NO:
- 2) binding stably to HLA molecules of the B27 type,
- (49)VYDFAFRDL(57) (residues 49 to 57 of SEQ ID NO:
- 2) binding stably to HLA molecules of the A24 type,
- (50)YDFAFRDL(57) (residues 50 to 57 of SEQ ID NO:
- 2) binding stably to HLA molecules of the A29, B44 type,
- (52)FAFRDLCIV(60) (residues 52 to 60 of SEQ ID NO:
- 2) binding stably to HLA molecules of the A2, B35, B51 type,
- (54)FRDLCIVYR(62) (residues 54 to 62 of SEQ ID NO:
- 2) binding stably to HLA molecules of the A3, A11 type,
- (59)IVYRDGNPY(67) (residues 59 to 67 of SEQ ID NO:
- 2) binding stably to HLA molecules of the A3, A11 type,
- (81)SEYRHYCY(88) (residues 81 to 88 of SEQ ID NO:
- 2) binding stably to HLA molecules of the A29, B44 type,
- (87)CYSLYGTTL(95) (residues 87 to 95 of SEQ ID NO:
- 2) binding stably to HLA molecules of the A24 type,
- (94)TLEQQYNK(101) (residues 94 to 101 of SEQ ID NO:
- 2) binding stably to HLA molecules of the A3, A11 type,
- (95)LEQQYNKPL(103) (residues 95 to 103 of SEQ ID NO:
- 2) binding stably to HLA molecules of the A29, B44 type,
- (101)KPLCDLLI(108) (residues 101 to 108 of SEQ ID NO:
- 2) binding stably to HLA molecules of the B7, B35, B51 type,
- (118)CPEEKQRHL(126) (residues 118 to 126 of SEQ ID NO:
- 2) binding stably to HLA molecules of the B8, B18, B35, B51 type,
- (119)PEEKQRHL(126) (residues 119 to 126 of SEQ ID NO:
- 2) binding stably to HLA molecules of the B44 type,
- (127)DKKQRFHNI(135) (residues 127 to 135 of SEQ ID NO:
- 2) binding stably to HLA molecules of the B8 type,
- (128)KKQRFHNIR(136) (residues 128 to 136 of SEQ ID NO:
- 2) binding stably to HLA molecules of the B27 type,
- (130)QRFHNIRGRW(139) (residues 130 to 139 of SEQ ID NO:
- 2) binding stably to HLA molecules of the B27 type,
- (131)RFHNIRGRW(139) (residues 131 to 139 of SEQ ID NO:
- 2) binding stably to HLA molecules of the A24 type.
Epitopes of the E7 protein of HPV selected from the following:
- (3)GDTPTLHEY(11) (residues 3 to 11 of SEQ ID NO:
- 12) binding stably to HLA molecules of the B44 type,
- (5)TPTLHEYML(13) (residues 5 to 13 of SEQ ID NO:
- 12) binding stably to HLA molecules of the B35 type,
- (15)LQPETTDLY(23) (residues 15 to 23 of SEQ ID NO:
- 12) binding stably to HLA molecules of the B62 type,
- (16)QPETTDLYCY(25) (residues 16 to 25 of SEQ ID NO:
- 12) binding stably to HLA molecules of the A1, B18 type,
- (45)AEPDRAHY(52) (residues 45 to 52 of SEQ ID NO:
- 12) binding stably to HLA molecules of the A29, B44 type,
- (46)EPDRAHYNIV(55) (residues 46 to 55 of SEQ ID NO:
- 12) binding stably to HLA molecules of the B7 or B35 type,
- (53)NIVTFCCK(60) (residues 53 to 60 of SEQ ID NO:
- 12) binding stably to HLA molecules of the A3, A11 type,
- (79)LEDLLMGTL(87) (residues 79 to 87 of SEQ ID NO:
- 12) binding stably to HLA molecules of the A29, B44 type,
- (89)IVCPICSQK(97) (residues 89 to 97 of SEQ ID NO:
- 12) binding stably to HLA molecules of the A3, A11 type.
Dependencies are inferred from the claim text.