Immunotherapy regimens in hiv-infected patients

• US 20060094006A1
• Filed: 05/01/2003
• Published: 05/04/2006
• Est. Priority Date: 05/01/2002
• Status: Abandoned Application

• Current Assignee: United States Department Of Health And Human Services (Government of the United States of America), Sanofi Pasteur Limited (Sanofi )
• Original Assignee: Sanofi Pasteur Limited (Sanofi )
• Inventors: Franchini, Genoveffa, Tartaglia, James
• Application Number:
  US10/513,257
• Publication Number:
  US 20060094006A1
• Time in Patent Office: Days
• US Class Current: 435/5
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/5256 expressing foreign proteins
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/55522 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/21 Retroviridae, e.g. equine infectious anemia virus
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 16/1063 env, e.g. gp41, gp110/120, gp160, V3, PND, CD4 binding site
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C12N 2710/24043 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2740/15022 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2740/15034 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2740/16034 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• 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 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

This invention relates to an improved method of maintaining an immuno-protective response in persons infected with a retrovirus during early infection or after highly active anti-retroviral therapy.

Claims

1. A method to potentiate a CD8⁺ or a CD4⁺ response to a human immunodeficiency virus-I (HIV-1) epitope in a human comprising:

administering at least one nucleic acid vaccine that encodes at least one human immunodeficiency virus-1 epitope to the human; and

administering at least one viral vaccine that encodes at least one human immunodeficiency virus-1 epitope to the human, wherein the nucleic acid vaccine and the viral vaccine can be administered to the human together or in any order.

2. The method of claim 1, further comprising administration of at least one anti-viral agent to the human, wherein the anti-viral agent can be administered together with the viral vaccine and the nucleic acid vaccine, or in any order.

3. The method of claim 1, further comprising administration of at least one agent that reduces human immunodeficiency virus-1 infectivity, wherein the agent can be administered together with the viral vaccine and the nucleic acid vaccine, or in any order.

4. The method according to any one of claims 1-3, further comprising administration of at least one immunoconjugate to the human.

5. The method according to any one of claims 1-3, further comprising administration of at least one cytokine to the human.

6. The method of claim 1, wherein administration of the viral vaccine and the nucleic acid vaccine potentiates a CD8⁺ or CD4⁺ response that is greater in magnitude than administration of the viral vaccine or the nucleic acid vaccine alone.

7. The method of claim 1, wherein the human has a viral load that is less than 10,000 viral copies per milliliter of plasma.

8. The method of claim 1, wherein the human has a viral load that is less than 5,000 viral copies per milliliter of plasma.

9. The method of claim 1, wherein the human has a viral load that is less than 2,000 viral copies per milliliter of plasma.

10. The method of claim 1, wherein the human has a CD4⁺ cell count above 300 cells per milliliter.

11. The method of claim 1, wherein the human has a CD4⁺ cell count above 400 cells per milliliter.

12. The method of claim 1, wherein the human has a CD4⁺ cell count above 500 cells per milliliter.

13. The method of claim 1, wherein the human has a viral load of less than 10,000 viral copies per milliliter of plasma, a CD4⁺ cell count above 400 cells per milliliter, and has been treated with one or more anti-viral agents that lowered viral load and increased CD4⁺ count in the human relative to the viral load and CD4⁺ count in the human before treatment with the anti-viral agent.

14. The method of claim 1, wherein the nucleic acid vaccine encodes at least one structural protein or at least one non-structural protein.

15. The method of claim 14, wherein the structural protein is selected from the group consisting of gp160, gp120, and gp41.

16. The method of claim 14, wherein the structural protein is encoded by a gene selected from the group consisting of env, pol, or gag.

17. The method of claim 14, wherein the non-structural protein is encoded by a gene selected from the group consisting of rev, tat, nef, vif, vpr, and vpu.

18. The method of claim 1, wherein the viral vaccine is a live viral vaccine or dead viral vaccine.

19. The method of claim 1, wherein the viral vaccine is an attenuated recombinant pox virus vaccine.

20. The method of claim 19, wherein the attenuated recombinant pox virus is selected from the group consisting of NYVAC, ALVAC, and fowlpox.

21. The method of claim 3, wherein the agent that reduces human immunodeficiency virus-1 infectivity is selected from the group consisting of an HIV-1 neutralizing antibody, a peptide that binds to an HIV-1 receptor, and a small molecule that binds to an HIV-1 receptor or an HIV-1 coreceptor.

22. The method of claim 21, wherein the HIV-1 neutralizing antibody binds to gp160, gp120, gp41, a CD4 receptor, a CCR5 receptor, or a CXCR4 receptor.

23. The method of claim 21, wherein the HIV-1 neutralizing antibody is selected from the group consisting of IgG b12, 2F5, 2G12, IgG2, and PRO 140.

24. The method of claim 21, wherein the peptide that binds to an HIV-1 receptor is selected from the group consisting of T-20, PRO 542, DP-178, and RANTES.

25. The method of claim 21, wherein the peptide that binds to the small molecule that binds to an HIV-1 receptor or an HIV-1 coreceptor is selected from the group consisting of TAK-779, AMD-3100, AMD-070, and SCH 351125.

26. The method of claim 4, wherein the immunoconjugate comprises a cytotoxic component and an antibody component that binds to HIV-1 protein expressed on an infected cell.

27. The method of claim 26, wherein the cytotoxic component is selected from the group consisting of Pseudomonas exotoxin, diphtheria toxin, an RNAase, and a radio-label.

28. The method of claim 5, wherein the cytokine is selected from the group consisting of interleukin-2, interleukin-7, interleukin-12, interleukin-15, macrophage colony stimulating factor, interferon beta, and CD40 ligand.

29. The method of claim 2, wherein the anti-viral agent is an anti-retroviral agent.

30. The method of claim 29, wherein the anti-retroviral agent is selected from the group consisting of a protease inhibitor, an HIV entry inhibitor, a reverse transcriptase inhibitor, and an anti-retroviral nucleoside analog.

31. The method of claim 1, further comprising administration of at least one anti-viral agent to the human, and at least one agent that reduces human immunodeficiency virus-1 infectivity, wherein the anti-viral agent and the agent that reduces human immunodeficiency virus-1 infectivity can be administered together with the viral vaccine and the nucleic acid vaccine, or in any order.

32. The method according to claim 31, further comprising administration of at least one immunoconjugate to the human.

33. The method according to any one of claims 31 or 32, further comprising administration of at least one cytokine to the human.