1887

Abstract

Candidate human immunodeficiency virus (HIV) vaccine strategies that induce strong cellular immune responses protect rhesus macaques that are infected with recombinant simian/human immunodeficiency virus SHIV89.6p from acute CD4 T-cell loss and delay progression to AIDS. However, similar strategies have not proven as efficacious in the simian immunodeficiency virus (SIV)mac model of AIDS, an infection that causes a slow, steady loss of CD4 T-cell function and numbers in rhesus macaques similar to that caused by HIV-1, the principal cause of AIDS in humans. Efforts to increase vaccine efficacy by repeated boosting with the same vector are quickly limited by rising anti-vector immune responses. Here, the sequential use of three different vectors (DNA, Semliki Forest virus and modified vaccinia virus Ankara) encoding the same SIVmac structural and regulatory antigens was investigated and demonstrated to prevent or slow the loss of CD4 T-cells after mucosal challenge with the highly pathogenic SIVmac251 strain. Of particular interest was an inverse association between the extent of T-helper 2 cytokine responses and steady-state virus load. Although limited in the number of animals, this study provides important proof of the efficacy of the triple-vector vaccine strategy against chronic, progressive CD4 T-cell loss in the rigorous SIVmac/rhesus macaque model of AIDS.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80226-0
2004-10-01
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/85/10/vir852915.html?itemId=/content/journal/jgv/10.1099/vir.0.80226-0&mimeType=html&fmt=ahah

References

  1. Allen T. M., Vogel T. U., Fuller D. H. 11 other authors 2000; Induction of AIDS virus-specific CTL activity in fresh, unstimulated peripheral blood lymphocytes from rhesus macaques vaccinated with a DNA prime/modified vaccinia virus Ankara boost regimen. J Immunol 164:4968–4978 [CrossRef]
    [Google Scholar]
  2. Allen T. M., Mortara L., Mothé B. R. 14 other authors 2002; Tat-vaccinated macaques do not control simian immunodeficiency virus SIVmac239 replication. J Virol 76:4108–4112 [CrossRef]
    [Google Scholar]
  3. Amara R. R., Villinger F., Altman J. D. 19 other authors 2001; Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine. Science 292:69–74 [CrossRef]
    [Google Scholar]
  4. Barouch D. H., Santra S., Kuroda M. J. 13 other authors 2001; Reduction of simian-human immunodeficiency virus 89.6P viremia in rhesus monkeys by recombinant modified vaccinia virus Ankara vaccination. J Virol 75:5151–5158 [CrossRef]
    [Google Scholar]
  5. Benson J., Chougnet C., Robert-Guroff M. 10 other authors 1998; Recombinant vaccine-induced protection against the highly pathogenic simian immunodeficiency virus SIVmac251: dependence on route of challenge exposure. J Virol 72:4170–4182
    [Google Scholar]
  6. Casimiro D. R., Chen L., Fu T.-M. 36 other authors 2003; Comparative immunogenicity in rhesus monkeys of DNA plasmid, recombinant vaccinia virus, and replication-defective adenovirus vectors expressing a human immunodeficiency virus type 1 gag gene. J Virol 77:6305–6313 [CrossRef]
    [Google Scholar]
  7. Douek D. C., Brenchley J. M., Betts M. R. 13 other authors 2002; HIV preferentially infects HIV-specific CD4+ T cells. Nature 417:95–98 [CrossRef]
    [Google Scholar]
  8. Hanke T., Blanchard T. J., Schneider J., Hannan C. M., Becker M., Gilbert S. C., Hill A. V. S., Smith G. L., McMichael A. 1998; Enhancement of MHC class I-restricted peptide-specific T cell induction by a DNA prime/MVA boost vaccination regime. Vaccine 16:439–445 [CrossRef]
    [Google Scholar]
  9. Heeney J. L. 2002; The critical role of CD4+ T-cell help in immunity to HIV. Vaccine 20:1961–1963 [CrossRef]
    [Google Scholar]
  10. Horton H., Vogel T. U., Carter D. K. 15 other authors 2002; Immunization of rhesus macaques with a DNA prime/modified vaccinia virus Ankara boost regimen induces broad simian immunodeficiency virus (SIV)-specific T-cell responses and reduces initial viral replication but does not prevent disease progression following challenge with pathogenic SIVmac239. J Virol 76:7187–7202 [CrossRef]
    [Google Scholar]
  11. Jin X., Bauer D. E., Tuttleton S. E. 11 other authors 1999; Dramatic rise in plasma viremia after CD8+ T cell depletion in simian immunodeficiency virus-infected macaques. J Exp Med 189:991–998 [CrossRef]
    [Google Scholar]
  12. Koopman G., Niphuis H., Newman W., Kishimoto T. K., Maino V. C., Heeney J. L. 2001; Decreased expression of IL-2 in central and effector CD4 memory cells during progression to AIDS in rhesus macaques. AIDS 15:2359–2369 [CrossRef]
    [Google Scholar]
  13. Langlois A. J., Desrosiers R. C., Lewis M. G. 7 other authors 1998; Neutralizing antibodies in sera from macaques immunized with attenuated simian immunodeficiency virus. J Virol 72:6950–6955
    [Google Scholar]
  14. Letvin N. L., Barouch D. H., Montefiori D. C. 2002; Prospects for vaccine protection against HIV-1 infection and AIDS. Annu Rev Immunol 20:73–99 [CrossRef]
    [Google Scholar]
  15. Mascola J. R., Stiegler G., VanCott T. C. 8 other authors 2000; Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies. Nat Med 6:207–210 [CrossRef]
    [Google Scholar]
  16. Montefiori D. C., Baba T. W., Li A., Bilska M., Ruprecht R. M. 1996; Neutralizing and infection-enhancing antibody responses do not correlate with the differential pathogenicity of SIVmac239delta3 in adult and infant rhesus monkeys. J Immunol 157:5528–5535
    [Google Scholar]
  17. Negri D. R. M., Baroncelli S., Catone S. 15 other authors 2004; Protective efficacy of a multicomponent vector vaccine in cynomolgus monkeys after intrarectal simian immunodeficiency virus challenge. J Gen Virol 85:1191–1201 [CrossRef]
    [Google Scholar]
  18. Nehete P. N., Chitta S., Hossain M. M., Hill L., Bernacky B. J., Baze W., Arlinghaus R. B., Sastry K. J. 2001; Protection against chronic infection and AIDS by an HIV envelope peptide-cocktail vaccine in a pathogenic SHIV-rhesus model. Vaccine 20:813–825 [CrossRef]
    [Google Scholar]
  19. Nilsson C., Mäkitalo B., Berglund P. 8 other authors 2001; Enhanced simian immunodeficiency virus-specific immune responses in macaques induced by priming with recombinant Semliki Forest virus and boosting with modified vaccinia virus Ankara. Vaccine 19:3526–3536 [CrossRef]
    [Google Scholar]
  20. Norley S., Beer B., Binninger-Schinzel D., Cosma C., Kurth R. 1996; Protection from pathogenic SIVmac challenge following short-term infection with a Nef-deficient attenuated virus. Virology 219:195–205 [CrossRef]
    [Google Scholar]
  21. Rhodes G. H., Abai A. M., Margalith M., Kuwahara-Rundell A., Morrow J., Parker S. E., Dwarki V. J. 1994; Characterization of humoral immunity after DNA injection. Dev Biol Stand 82:229–236
    [Google Scholar]
  22. Robinson H. L., Montefiori D. C., Johnson R. P. 14 other authors 1999; Neutralizing antibody-independent containment of immunodeficiency virus challenges by DNA priming and recombinant pox virus booster immunizations. Nat Med 5:526–534 [CrossRef]
    [Google Scholar]
  23. Rose N. F., Marx P. A., Luckay A. 7 other authors 2001; An effective AIDS vaccine based on live attenuated vesicular stomatitis virus recombinants. Cell 106:539–549 [CrossRef]
    [Google Scholar]
  24. Schmitz J. E., Kuroda M. J., Santra S. 13 other authors 1999; Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 283:857–860 [CrossRef]
    [Google Scholar]
  25. Sharpe S., Polyanskaya N., Dennis M., Sutter G., Hanke T., Erfle V., Hirsch V., Cranage M. 2001; Induction of simian immunodeficiency virus (SIV)-specific CTL in rhesus macaques by vaccination with modified vaccinia virus Ankara expressing SIV transgenes: influence of pre-existing anti-vector immunity. J Gen Virol 82:2215–2223
    [Google Scholar]
  26. Shiver J. W., Fu T.-M., Chen L. 49 other authors; 2002; Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature 415:331–335 [CrossRef]
    [Google Scholar]
  27. Stittelaar K. J., Gruters R. A., Schutten M., van Baalen C. A., van Amerongen G., Cranage M., Liljeström P., Sutter G., Osterhaus A. D. M. E. 2002; Comparison of the efficacy of early versus late viral proteins in vaccination against SIV. Vaccine 20:2921–2927 [CrossRef]
    [Google Scholar]
  28. ten Haaft P., Verstrepen B., Uberla K., Rosenwirth B., Heeney J. 1998; A pathogenic threshold of virus load defined in simian immunodeficiency virus- or simian-human immunodeficiency virus-infected macaques. J Virol 72:10281–10285
    [Google Scholar]
  29. ten Haaft P., Almond N., Biberfeld G. 9 other authors 2001; Comparison of early plasma RNA loads in different macaque species and the impact of different routes of exposure on SIV/SHIV infection. J Med Primatol 30:207–214 [CrossRef]
    [Google Scholar]
  30. Veazey R. S., Tham I. C., Mansfield K. G., DeMaria M., Forand A. E., Shvetz D. E., Chalifoux L. V., Sehgal P. K., Lackner A. A. 2000; Identifying the target cell in primary simian immunodeficiency virus (SIV) infection: highly activated memory CD4+ T cells are rapidly eliminated in early SIV infection in vivo. J Virol 74:57–64 [CrossRef]
    [Google Scholar]
  31. Verschoor E. J., Mooij P., Oostermeijer H. 9 other authors 1999; Comparison of immunity generated by nucleic acid-, MF59-, and ISCOM-formulated human immunodeficiency virus type 1 vaccines in rhesus macaques: evidence for viral clearance. J Virol 73:3292–3300
    [Google Scholar]
  32. Vogel T. U., Beer B. E., zur Megede J. 7 other authors 2002a; Induction of anti-simian immunodeficiency virus cellular and humoral immune responses in rhesus macaques by peptide immunogens: correlation of CTL activity and reduction of cell-associated but not plasma virus load following challenge. J Gen Virol 83:81–91
    [Google Scholar]
  33. Vogel T. U., Horton H., Fuller D. H. 10 other authors 2002b; Differences between T cell epitopes recognized after immunization and after infection. J Immunol 169:4511–4521 [CrossRef]
    [Google Scholar]
  34. Yasutomi Y., Koenig S., Woods R. M. 10 other authors 1995; A vaccine-elicited, single viral epitope-specific cytotoxic T lymphocyte response does not protect against intravenous, cell-free simian immunodeficiency virus challenge. J Virol 69:2279–2284
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.80226-0
Loading
/content/journal/jgv/10.1099/vir.0.80226-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error