1887

Abstract

To further investigate mechanisms of protective immunity that are induced by live, attenuated simian immunodeficiency virus (SIV), three macaques were infected with SIVmacGX2, a -disrupted molecular clone. In two of these animals, which expressed the MamuA*01 major histocompatibility complex class I allele, loss of functional activity against an SIV-Gag-encoded immunodominant cytotoxic T lymphocyte (CTL) epitope was observed following prolonged infection. Nonetheless, all three animals were resistant to challenge with an uncloned pool of wild-type SIVmac, whereas four naïve controls became infected. Tetramer staining revealed the rapid generation of CD8 T-cell responses against - and -encoded immunodominant epitopes in MamuA*01 challenge controls. The dynamics of these T-cell responses to the wild-type virus were similar to those observed following primary infection of the vaccine group with attenuated virus. In contrast, neither tetramer staining nor gamma interferon ELISpot assay revealed an immediate, systemic, anamnestic response in the wild-type-challenged, attenuated SIV-infected animals. Functional CTL capacity had not been lost in this group, as lytic activity was still evident 17 weeks after challenge. Both attenuated and wild-type viruses induced a disseminated CD8 T-cell response, which was of a higher magnitude in lymphoid tissues than in the periphery. These results suggest that, at least as measured in the periphery, protection against wild-type infection that is induced by live, attenuated SIV is not dependent on a rechallenge-driven expansion of immunodominant epitope-specific CD8 T cells and, therefore, pre-existing activity may be sufficient to prevent superinfection.

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2004-09-01
2019-10-22
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References

  1. Allen, T. M., Sidney, J., del Guercio, M.-F. & 8 other authors ( 1998; ). Characterization of the peptide binding motif of a rhesus MHC class I molecule (Mamu-A*01) that binds an immunodominant CTL epitope from simian immunodeficiency virus. J Immunol 160, 6062–6071.
    [Google Scholar]
  2. Allen, T. M., O'Connor, D. H., Jing, P. & 16 other authors ( 2000; ). Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia. Nature 407, 386–390.[CrossRef]
    [Google Scholar]
  3. Allen, T. M., Mothé, B. R., Sidney, J. & 11 other authors ( 2001; ). CD8+ lymphocytes from simian immunodeficiency virus-infected rhesus macaques recognize 14 different epitopes bound by the major histocompatibility complex class I molecule MamuA*01: implications for vaccine design and testing. J Virol 75, 738–749.[CrossRef]
    [Google Scholar]
  4. Almond, N. & Stott, J. ( 1999; ). Live attenuated SIV – a model of a vaccine for AIDS. Immunol Lett 66, 167–170.[CrossRef]
    [Google Scholar]
  5. Almond, N., Kent, K., Cranage, M., Rud, E., Clarke, B. & Stott, E. J. ( 1995; ). Protection by attenuated simian immunodeficiency virus in macaques against challenge with virus-infected cells. Lancet 345, 1342–1344.[CrossRef]
    [Google Scholar]
  6. Almond, N., Rose, J., Sangster, R., Silvera, P., Stebbings, R., Walker, B. & Stott, E. J. ( 1997; ). Mechanisms of protection induced by attenuated simian immunodeficiency virus. I. Protection cannot be transferred with immune serum. J Gen Virol 78, 1919–1922.
    [Google Scholar]
  7. Arnold, C., Jenkins, A., Almond, N., Stott, E. J. & Kent, K. A. ( 1999; ). Monoclonal antibodies recognize at least five epitopes on the SIV Nef protein and identify an in vitro-induced mutation. AIDS Res Hum Retrovir 15, 1087–1097.[CrossRef]
    [Google Scholar]
  8. Baba, T. W., Jeong, Y. S., Pennick, D., Bronson, R., Greene, M. F. & Ruprecht, R. M. ( 1995; ). Pathogenicity of live, attenuated SIV after mucosal infection of neonatal macaques. Science 267, 1820–1825.[CrossRef]
    [Google Scholar]
  9. Baba, T. W., Liska, V., Khimani, A. H. & 8 other authors ( 1999; ). Live attenuated, multiply deleted simian immunodeficiency virus causes AIDS in infant and adult macaques. Nat Med 5, 194–203.[CrossRef]
    [Google Scholar]
  10. Bogers, W. M. J. M., Niphuis, H., ten Haaft, P., Laman, J. D., Koornstra, W. & Heeney, J. L. ( 1995; ). Protection from HIV-1 envelope-bearing chimeric simian immunodeficiency virus (SHIV) in rhesus macaques infected with attenuated SIV: consequences of challenge. AIDS 9, F13–F18.
    [Google Scholar]
  11. 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]
  12. Clarke, S., Almond, N. & Berry, N. ( 2003; ). Simian immunodeficiency virus Nef gene regulates the production of 2-LTR circles in vivo. Virology 306, 100–108.[CrossRef]
    [Google Scholar]
  13. Connor, R. I., Montefiori, D. C., Binley, J. M. & 8 other authors ( 1998; ). Temporal analyses of virus replication, immune responses, and efficacy in rhesus macaques immunized with a live, attenuated simian immunodeficiency virus vaccine. J Virol 72, 7501–7509.
    [Google Scholar]
  14. Cranage, M. P., Whatmore, A. M., Sharpe, S. A. & 7 other authors ( 1997; ). Macaques infected with live attenuated SIVmac are protected against superinfection via the rectal mucosa. Virology 229, 143–154.[CrossRef]
    [Google Scholar]
  15. Cranage, M. P., Sharpe, S. A., Whatmore, A. M., Polyanskaya, N., Norley, S., Cook, N., Leech, S., Dennis, M. J. & Hall, G. A. ( 1998; ). In vivo resistance to simian immunodeficiency virus superinfection depends on attenuated virus dose. J Gen Virol 79, 1935–1944.
    [Google Scholar]
  16. Daniel, M. D., Kirchhoff, F., Czajak, S. C., Sehgal, P. K. & Desrosiers, R. C. ( 1992; ). Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene. Science 258, 1938–1941.[CrossRef]
    [Google Scholar]
  17. Dittmer, U., Nißlein, T., Bodemer, W., Petry, H., Sauermann, U., Stahl-Hennig, C. & Hunsmann, G. ( 1995; ). Cellular immune response of rhesus monkeys infected with a partially attenuated nef deletion mutant of the simian immunodeficiency virus. Virology 212, 392–397.[CrossRef]
    [Google Scholar]
  18. Flynn, K. J., Riberdy, J. M., Christensen, J. P., Altman, J. D. & Doherty, P. C. ( 1999; ). In vivo proliferation of naïve and memory influenza-specific CD8+ T cells. Proc Natl Acad Sci U S A 96, 8597–8602.[CrossRef]
    [Google Scholar]
  19. Geretti, A.-M., Hulskotte, E. G. J., Dings, M. E. M., van Baalen, C. A., van Amerongen, G., Norley, S. G., Boers, P., Gruters, R. & Osterhaus, A. D. M. E. ( 1999; ). Decline of simian immunodeficiency virus (SIV)-specific cytotoxic T lymphocytes in the peripheral blood of long-term nonprogressing macaques infected with SIVmac32H-J5. J Infect Dis 180, 1133–1141.[CrossRef]
    [Google Scholar]
  20. Gundlach, B. R., Reiprich, S., Sopper, S., Means, R. E., Dittmer, U., Mätz-Rensing, K., Stahl-Hennig, C. & Überla, K. ( 1998; ). Env-independent protection induced by live, attenuated simian immunodeficiency virus vaccines. J Virol 72, 7846–7851.
    [Google Scholar]
  21. Hofmann-Lehmann, R., Vlasak, J., Williams, A. L., Chenine, A.-L., McClure, H. M., Anderson, D. C., O'Neil, S. & Ruprecht, R. M. ( 2003; ). Live attenuated, nef-deleted SIV is pathogenic in most adult macaques after prolonged observation. AIDS 17, 157–166.[CrossRef]
    [Google Scholar]
  22. Home Office ( 1989; ). Code of Practice for the Housing and Care of Animals used in Scientific Procedures. London: HMSO.
  23. Johnson, R. P. & Desrosiers, R. C. ( 1998; ). Protective immunity induced by live attenuated simian immunodeficiency virus. Curr Opin Immunol 10, 436–443.[CrossRef]
    [Google Scholar]
  24. Johnson, R. P., Glickman, R. L., Yang, J. Q., Kaur, A., Dion, J. T., Mulligan, M. J. & Desrosiers, R. C. ( 1997; ). Induction of vigorous cytotoxic T-lymphocyte responses by live attenuated simian immunodeficiency virus. J Virol 71, 7711–7718.
    [Google Scholar]
  25. Khatissian, E., Monceaux, V., Cumont, M.-C., Kieny, M.-P., Aubertin, A.-M. & Hurtrel, B. ( 2001; ). Persistence of pathogenic challenge virus in macaques protected by simian immunodeficiency virus SIVmacΔnef. J Virol 75, 1507–1515.[CrossRef]
    [Google Scholar]
  26. 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]
  27. 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]
  28. Kuroda, M. J., Schmitz, J. E., Seth, A. & 8 other authors ( 2000; ). Simian immunodeficiency virus-specific cytotoxic T lymphocytes and cell-associated viral RNA levels in distinct lymphoid compartments of SIVmac-infected rhesus monkeys. Blood 96, 1474–1479.
    [Google Scholar]
  29. Lohman, B. L., McChesney, M. B., Miller, C. J. & 7 other authors ( 1994; ). A partially attenuated simian immunodeficiency virus induces host immunity that correlates with resistance to pathogenic virus challenge. J Virol 68, 7021–7029.
    [Google Scholar]
  30. McKay, P. F., Schmitz, J. E., Barouch, D. H., Kuroda, M. J., Lifton, M. A., Nickerson, C. E., Gorgone, D. A. & Letvin, N. L. ( 2002; ). Vaccine protection against functional CTL abnormalities in simian human immunodeficiency virus-infected rhesus monkeys. J Immunol 168, 332–337.[CrossRef]
    [Google Scholar]
  31. Metzner, K. J., Jin, X., Lee, F. V. & 8 other authors ( 2000; ). Effects of in vivo CD8+ T cell depletion on virus replication in rhesus macaques immunized with a live, attenuated simian immunodeficiency virus vaccine. J Exp Med 191, 1921–1931.[CrossRef]
    [Google Scholar]
  32. Nilsson, C., Mäkitalo, B., Thorstensson, R., Norley, S., Binninger-Schinzel, D., Cranage, M., Rud, E., Biberfeld, G. & Putkonen, P. ( 1998; ). Live attenuated simian immunodeficiency virus (SIV)mac in macaques can induce protection against mucosal infection with SIVsm. AIDS 12, 2261–2270.[CrossRef]
    [Google Scholar]
  33. Nixon, D. F., Donahoe, S. M., Kakimoto, W. M., Samuel, R. V., Metzner, K. J., Gettie, A., Hanke, T., Marx, P. A. & Connor, R. I. ( 2000; ). Simian immunodeficiency virus-specfic cytotoxic T lymphocytes and protection against challenge in rhesus macaques immunized with a live attenuated simian immunodeficiency virus vaccine. Virology 266, 203–210.[CrossRef]
    [Google Scholar]
  34. 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]
  35. Polyanskaya, N., Sharpe, S., Cook, N., Leech, S., Banks, J., Dennis, M., Hall, G., Stott, J. & Cranage, M. ( 1997; ). Anti-major histocompatibility complex antibody responses to simian B cells do not protect macaques against SIVmac infection. AIDS Res Hum Retrovir 13, 923–931.[CrossRef]
    [Google Scholar]
  36. Rinaldo, C. R., Jr, Huang, X.-L., Fan, Z. & 9 other authors ( 2000; ). Anti-human immunodeficiency virus type 1 (HIV-1) CD8+ T-lymphocyte reactivity during combination antiretroviral therapy in HIV-1-infected patients with advanced immunodeficiency. J Virol 74, 4127–4138.[CrossRef]
    [Google Scholar]
  37. Rud, E. W., Cranage, M., Yon, J., Quirk, J., Ogilvie, L., Cook, N., Webster, S., Dennis, M. & Clarke, B. E. ( 1994; ). Molecular and biological characterization of simian immunodeficiency virus macaque strain 32H proviral clones containing nef size variants. J Gen Virol 75, 529–543.[CrossRef]
    [Google Scholar]
  38. Sawai, E. T., Hamza, M. S., Ye, M., Shaw, K. E. & Luciw, P. A. ( 2000; ). Pathogenic conversion of live attenuated simian immunodeficiency virus vaccines is associated with expression of truncated Nef. J Virol 74, 2038–2045.[CrossRef]
    [Google Scholar]
  39. Sharpe, S. A., Whatmore, A. M., Hall, G. A. & Cranage, M. P. ( 1997; ). Macaques infected with attenuated simian immunodeficiency virus resist superinfection with virulence-revertant virus. J Gen Virol 78, 1923–1927.
    [Google Scholar]
  40. Sharpe, S., Hanke, T., Tinsley-Bown, A., Dennis, M., Dowall, S., McMichael, A. & Cranage, M. ( 2003; ). Mucosal immunization with PLGA-microencapsulated DNA primes a SIV-specific CTL response revealed by boosting with cognate recombinant modified vaccinia virus Ankara. Virology 313, 13–21.[CrossRef]
    [Google Scholar]
  41. Stebbings, R., Stott, J., Almond, N. & 10 other authors ( 1998; ). Mechanisms of protection induced by attenuated simian immunodeficiency virus. II. Lymphocyte depletion does not abrogate protection. AIDS Res Hum Retrovir 14, 1187–1198.[CrossRef]
    [Google Scholar]
  42. Stebbings, R. J., Almond, N. M., Stott, E. J. & 9 other authors ( 2002; ). Mechanisms of protection induced by attenuated simian immunodeficiency virus. V. No evidence for lymphocyte-regulated cytokine responses upon rechallenge. Virology 296, 338–353.[CrossRef]
    [Google Scholar]
  43. Stott, E. J., Almond, N., West, W., Kent, K., Cranage, M. & Rud, E. ( 1994; ). Protection against simian immunodeficiency virus infection of macaques by cellular or viral antigens. In Neuvieme Colloque Des Cent Gardes, pp. 219–224. Edited by M. Girard & L. Vallette. Lyon, France: Fondation Marcel Merieux.
  44. Ten Haaft, P., Verstrepen, B., Überla, 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]
  45. Whatmore, A. M., Cook, N., Hall, G. A., Sharpe, S., Rud, E. W. & Cranage, M. P. ( 1995; ). Repair and evolution of nef in vivo modulates simian immunodeficiency virus virulence. J Virol 69, 5117–5123.
    [Google Scholar]
  46. Wyand, M. S., Manson, K. H., Garcia-Moll, M., Montefiori, D. & Desrosiers, R. C. ( 1996; ). Vaccine protection by a triple deletion mutant of simian immunodeficiency virus. J Virol 70, 3724–3733.
    [Google Scholar]
  47. Yasutomi, Y., Reimann, K. A., Lord, C. I., Miller, M. D. & Letvin, N. L. ( 1993; ). Simian immunodeficiency virus-specific CD8+ lymphocyte response in acutely infected rhesus monkeys. J Virol 67, 1707–1711.
    [Google Scholar]
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