1887

Abstract

Virus-specific cellular immune responses play an important role in the control of immunodeficiency virus replication. However, preclinical trials of vaccines that induce virus-specific cellular immune responses have failed to contain simian immunodeficiency virus (SIV) replication in macaques. A defective provirus DNA vaccine system that efficiently induces virus-specific CD8 T-cell responses has previously been developed. The vaccinated macaques showed reduced viral loads, but failed to contain SIVmac239 replication. In this study, macaques that showed partial control of SIV replication were followed up to see if or how they lost this control in the chronic phase. Two of them showed increased viral loads about 4 or 8 months after challenge and finally developed AIDS. Analysis of SIV-specific T-cell levels by detection of SIV-specific gamma interferon (IFN-) production revealed that these two macaques maintained SIV-specific CD8 T cells, even after loss of control, but lost SIV-specific CD4 T cells when plasma viral loads increased. The remaining macaque kept viral loads at low levels and maintained SIV-specific CD4 T cells, as well as CD8 T cells, for more than 3 years. Additional analysis using macaques vaccinated with a Gag-expressing Sendai virus vector also found loss of viraemia control, with loss of SIV-specific CD4 T cells in the chronic phase of SIV infection. Thus, SIV-specific CD4 T cells that were able to produce IFN- in response to SIV antigens were preserved by the vaccine-based partial control of primary SIV replication, but were lost with abrogation of control in the chronic phase.

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2004-07-01
2019-11-15
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References

  1. Albritton, L. M., Tseng, L., Scadden, D. & Cunningham, J. M. ( 1989; ). A putative murine ecotropic retrovirus receptor gene encodes a multiple membrane-spanning protein and confers susceptibility to virus infection. Cell 57, 659–666.[CrossRef]
    [Google Scholar]
  2. Altfeld, M. & Rosenberg, E. S. ( 2000; ). The role of CD4+ T helper cells in the cytotoxic T lymphocyte response to HIV-1. Curr Opin Immunol 12, 375–380.[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 in rhesus macaques by a multiprotein DNA/MVA vaccine. Science 292, 69–74.[CrossRef]
    [Google Scholar]
  4. Appay, V., Nixon, D. F., Donahoe, S. M. & 13 other authors ( 2000; ). HIV-specific CD8+ T cells produce antiviral cytokines but are impaired in cytolytic function. J Exp Med 192, 63–76.[CrossRef]
    [Google Scholar]
  5. Barouch, D. H., Santra, S., Schmitz, J. E. & 26 other authors ( 2000; ). Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination. Science 290, 486–492.[CrossRef]
    [Google Scholar]
  6. Borrow, P., Lewicki, H., Hahn, B. H., Shaw, G. M. & Oldstone, M. B. A. ( 1994; ). Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. J Virol 68, 6103–6110.
    [Google Scholar]
  7. Brander, C. & Walker, B. D. ( 1999; ). T lymphocyte responses in HIV-1 infection: implications for vaccine development. Curr Opin Immunol 11, 451–459.[CrossRef]
    [Google Scholar]
  8. Champagne, P., Ogg, G. S., King, A. S. & 12 other authors ( 2001; ). Skewed maturation of memory HIV-specific CD8 T lymphocytes. Nature 410, 106–111.[CrossRef]
    [Google Scholar]
  9. Feinberg, M. B. & Moore, J. P. ( 2002; ). AIDS vaccine models: challenging challenge viruses. Nat Med 8, 207–210.[CrossRef]
    [Google Scholar]
  10. Hamann, D., Baars, P. A., Rep, M. H. G., Hooibrink, B., Kerkhof-Garde, S. R., Klein, M. R. & van Lier, R. A. W. ( 1997; ). Phenotypic and functional separation of memory and effector human CD8+ T cells. J Exp Med 186, 1407–1418.[CrossRef]
    [Google Scholar]
  11. Harari, A., Petitpierre, S., Vallelian, F. & Pantaleo, G. ( 2004; ). Skewed representation of functionally distinct populations of virus-specific CD4 T cells in HIV-1-infected subjects with progressive disease: changes after antiretroviral therapy. Blood 103, 966–972.
    [Google Scholar]
  12. 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]
  13. Iyasere, C., Tilton, J. C., Johnson, A. J. & 13 other authors ( 2003; ). Diminished proliferation of human immunodeficiency virus-specific CD4+ T cells is associated with diminished interleukin-2 (IL-2) production and is recovered by exogenous IL-2. J Virol 77, 10900–10909.[CrossRef]
    [Google Scholar]
  14. 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]
  15. Kano, M., Matano, T., Nakamura, H., Takeda, A., Kato, A., Ariyoshi, K., Mori, K., Sata, T. & Nagai, Y. ( 2000; ). Elicitation of protective immunity against simian immunodeficiency virus infection by a recombinant Sendai virus expressing the Gag protein. AIDS 14, 1281–1282.[CrossRef]
    [Google Scholar]
  16. Kano, M., Matano, T., Kato, A., Nakamura, H., Takeda, A., Suzaki, Y., Ami, Y., Terao, K. & Nagai, Y. ( 2002; ). Primary replication of a recombinant Sendai virus vector in macaques. J Gen Virol 83, 1377–1386.
    [Google Scholar]
  17. Karlsson, G. B., Halloran, M., Li, J. & 7 other authors ( 1997; ). Characterization of molecularly cloned simian-human immunodeficiency viruses causing rapid CD4+ lymphocyte depletion in rhesus monkeys. J Virol 71, 4218–4225.
    [Google Scholar]
  18. Kato, A., Sakai, Y., Shioda, T., Kondo, T., Nakanishi, M. & Nagai, Y. ( 1996; ). Initiation of Sendai virus multiplication from transfected cDNA or RNA with negative or positive sense. Genes Cells 1, 569–579.[CrossRef]
    [Google Scholar]
  19. Kestler, H., Kodama, T., Ringler, D. & 8 other authors ( 1990; ). Induction of AIDS in rhesus monkeys by molecularly cloned simian immunodeficiency virus. Science 248, 1109–1112.[CrossRef]
    [Google Scholar]
  20. Koch, W., Hunsmann, G. & Friedrich, R. ( 1983; ). Nucleotide sequence of the envelope gene of Friend murine leukemia virus. J Virol 45, 1–9.
    [Google Scholar]
  21. Kostense, S., Ogg, G. S., Manting, E. H. & 8 other authors ( 2001; ). High viral burden in the presence of major HIV-specific CD8+ T cell expansions: evidence for impaired CTL effector function. Eur J Immunol 31, 677–686.[CrossRef]
    [Google Scholar]
  22. Koup, R. A., Safrit, J. T., Cao, Y., Andrews, C. A., McLeod, G., Borkowsky, W., Farthing, C. & Ho, D. D. ( 1994; ). Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J Virol 68, 4650–4655.
    [Google Scholar]
  23. Matano, T., Shibata, R., Siemon, C., Connors, M., Lane, H. C. & Martin, M. A. ( 1998; ). Administration of an anti-CD8 monoclonal antibody interferes with the clearance of chimeric simian/human immunodeficiency virus during primary infections of rhesus macaques. J Virol 72, 164–169.
    [Google Scholar]
  24. Matano, T., Kano, M., Odawara, T., Nakamura, H., Takeda, A., Mori, K., Sato, T. & Nagai, Y. ( 2000; ). Induction of protective immunity against pathogenic simian immunodeficiency virus by a foreign receptor-dependent replication of an engineered avirulent virus. Vaccine 18, 3310–3318.[CrossRef]
    [Google Scholar]
  25. Matano, T., Kano, M., Nakamura, H., Takeda, A. & Nagai, Y. ( 2001; ). Rapid appearance of secondary immune responses and protection from acute CD4 depletion after a highly pathogenic immunodeficiency virus challenge in macaques vaccinated with a DNA prime/Sendai virus vector boost regimen. J Virol 75, 11891–11896.[CrossRef]
    [Google Scholar]
  26. Matloubian, M., Concepcion, R. J. & Ahmed, R. ( 1994; ). CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection. J Virol 68, 8056–8063.
    [Google Scholar]
  27. Migueles, S. A., Laborico, A. C., Shupert, W. L. & 11 other authors ( 2002; ). HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors. Nat Immunol 3, 1061–1068.[CrossRef]
    [Google Scholar]
  28. Nathanson, N., Hirsch, V. M. & Mathieson, B. J. ( 1999; ). The role of nonhuman primates in the development of an AIDS vaccine. AIDS 13 (suppl. A), S113–S120.
    [Google Scholar]
  29. Ogg, G. S., Jin, X., Bonhoeffer, S. & 12 other authors ( 1998; ). Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. Science 279, 2103–2106.[CrossRef]
    [Google Scholar]
  30. 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]
  31. Rosenberg, E. S., Billingsley, J. M., Caliendo, A. M., Boswell, S. L., Sax, P. E., Kalams, S. A. & Walker, B. D. ( 1997; ). Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science 278, 1447–1450.[CrossRef]
    [Google Scholar]
  32. Sallusto, F., Lenig, D., Forster, R., Lipp, M. & Lanzavecchia, A. ( 1999; ). Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401, 708–712.[CrossRef]
    [Google Scholar]
  33. 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]
  34. Seder, R. A. & Hill, A. V. S. ( 2000; ). Vaccines against intracellular infections requiring cellular immunity. Nature 406, 793–798.[CrossRef]
    [Google Scholar]
  35. Shibata, R., Maldarelli, F., Siemon, C., Matano, T., Parta, M., Miller, G., Fredrickson, T. & Martin, M. A. ( 1997; ). Infection and pathogenicity of chimeric simian-human immunodeficiency viruses in macaques: determinants of high virus loads and CD4 cell killing. J Infect Dis 176, 362–373.[CrossRef]
    [Google Scholar]
  36. 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]
  37. Takeda, A., Nakamura, H. & Matano, T. ( 2000; ). Confined replication of a chimeric simian immunodeficiency virus. Jpn J Infect Dis 53, 209–211.
    [Google Scholar]
  38. Vogel, T. U., Allen, T. M., Altman, J. D. & Watkins, D. I. ( 2001; ). Functional impairment of simian immunodeficiency virus-specific CD8+ T cells during the chronic phase of infection. J Virol 75, 2458–2461.[CrossRef]
    [Google Scholar]
  39. Voss, G., Nick, S., Stahl-Hennig, C., Ritter, K. & Hunsmann, G. ( 1992; ). Generation of macaque B lymphoblastoid cell lines with simian Epstein-Barr-like viruses: transformation procedure, characterization of the cell lines and occurrence of simian foamy virus. J Virol Methods 39, 185–195.[CrossRef]
    [Google Scholar]
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