Polyvalent immunogen

• US 20040086506A1
• Filed: 05/08/2003
• Published: 05/06/2004
• Est. Priority Date: 11/07/2001
• Status: Active Grant

• Current Assignee: Duke University, Los Alamos National Security LLC (Government of the United States of America)
• Original Assignee: Duke University
• Inventors: Liao, Hua-Xin, Haynes, Barton F., Korber, Bette T., De Lorimier, Robert M.
• Granted Patent: US 7,172,761 B2
• Time in Patent Office: Days
• US Class Current: 424/144.1
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 2039/543 intranasal
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/55544 Bacterial toxins
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/21 Retroviridae, e.g. equine infectious anemia virus
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C12N 2740/16122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2740/16134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2740/16222 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: Y10S 530/826 Viruses

Abstract

The present invention relates, generally, to a polyvalent immunogen and, more particularly, to a method of inducing neutralizing antibodies against HIV and to a polyvalent immunogen suitable for use in such a method.

Claims

21. A composition comprising at least one peptide from Table 6 or Table 7 and a carrier.

22. The composition according to claim 21 wherein said composition further comprises an adjuvant.

27. A nucleic acid encoding a peptide in Table 6 or Table 7.

29. A method of inducing the production of neutralizing antibodies in a patient comprising administering to said patient an amount of said formulation according to claim 27 sufficient to effect said production.

30. An isolated polypeptide comprising a V3 sequence shown in Table 10, 11 or 12.

1. A composition comprising a multiplicity of immunogenic peptides comprising a first and a second component,

said first component comprising a T-helper epitope,

said second component comprising residues of the V3 domain of gp120 and including a B cell neutralizing antibody epitope.

2. The composition according to claim 1 wherein said first component is an a human immunodeficiency virus (HIV) T helper epitope.

3. The composition according to claim 2 wherein said first component comprises residues of the C4 domain of HIV gp120.

4. The composition according to claim 3 wherein said first component comprises at least 16 contiguous residues of the C4 domain of HIV gp120.

5. The composition according to claim 4 wherein said first component comprises residues 421 to 436 of the C4 domain of HIV gp120.

6. The composition according to claim 2 wherein said first component comprises residues of HIV p24 gag.

7. The composition according to claim 6 wherein said first component comprises GTH1 (residues 262-278 of HIV gag).

8. The composition according to claim 1 wherein said first component is a non-HIV T helper epitope.

9. The composition according to claim 1 wherein said second component comprises at least 23 contiguous residues of the V3 domain of HIV gp120.

10. The composition according to claim 9 wherein said second component comprises residues 297 to 322 of the V3 domain of HIV gp120.

11. The composition according to claim 1 wherein said first component comprises at least 16 contiguous residues of the C4 domain of HIV gp120 and said second component comprises at least 23 contiguous residues of the V3 domain of HIV gp120.

12. The composition according to claim 11 wherein said first component comprises residues 421 to 436 of the C4 domain of HIV gp120 and said second component comprises residues 297 to 322 of the V3 domain of HIV gp120.

13. The composition according to claim 1 wherein said second component is linked C terminal to said first component.

14. The composition according to claim 1 wherein said first component is linked to said second component via a linker.

15. The composition according to claim 1 wherein said composition comprises at least 5 immunogenic peptides.

16. The composition according to claim 15 wherein said composition comprises C4-V3 36.29, C4-V3 34.29, C4-V3 62.19, C4-V3 74.17 and C4-V3 162.7 from Table 7.

17. The composition according to claim 15 wherein said composition comprises at least 10 immunogenic peptides.

18. The composition according to claim 17 wherein said composition comprises at least 25 immunogenic peptides.

19. The composition according to claim 1 wherein said composition further comprises a carrier.

20. The composition according to claim 1 wherein said composition further comprises an adjuvant.

23. The composition according to claim 1 wherein second components are selected so as to be representative of higher order structural motifs present in a population, which motifs mediate V3 functions in the course of envelope mediated HIV interaction with host cells.

24. The composition according to claim 23 wherein said composition comprises about 25-30 immunogenic peptides the second components of which are selected so as to be representative of infected individuals within a subtype.

25. The composition according to claim 1 wherein at least one of said first components comprises the sequence KQIINMWQVVGKAMYA.

26. A method of inducing the production of neutralizing antibodies in a patient comprising administering to said patient an amount of the composition according to claim 1 sufficient to effect said production.

28. A formulation comprising at least one nucleic acid sequence encoding said composition of claim 1.

31. An isolated nucleic acid sequence encoding at least one polypeptide according to claim 30.

32. A vector comprising the nucleic acid according to claim 31.

33. A method of inducing the production of neutralizing antibodies in a mammal comprising administering to said mammal an amount of said polypeptide according to claim 30 or said nucleic acid sequence according to claim 31 sufficient to effect said induction.

34. A composition comprising said polypeptide according to claim 30 or said nucleic acid sequence according to claim 31 and a carrier.

35. The composition according to claim 1 wherein said first component comprises the sequence YKRWIILGLNKIVRM.

36. The composition according to claim 34 wherein said polypeptide is 62.19.

37. The method according to claim 33 wherein said method comprises administering said V3 sequence in a DNA prime with said V3 sequence in a gp120 boost.

38. The method according to claim 33 wherein said method comprises administering said V3 sequence in a DNA prime with said V3 sequence in a gp120, gp140 or gp160 replicating vector boost.

39. The method according to claim 33 wherein said method comprises administering a replicating vector comprising said V3 sequence in envelope as prime and boost.

37-1. The method according to claim 33 wherein said method comprises administering said V3 sequence in a DNA prime with said V3 sequence in a gp140 or gp160 boost.