Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1995 Apr;69(4):2279–2284. doi: 10.1128/jvi.69.4.2279-2284.1995

A vaccine-elicited, single viral epitope-specific cytotoxic T lymphocyte response does not protect against intravenous, cell-free simian immunodeficiency virus challenge.

Y Yasutomi 1, S Koenig 1, R M Woods 1, J Madsen 1, N M Wassef 1, C R Alving 1, H J Klein 1, T E Nolan 1, L J Boots 1, J A Kessler 1, et al.
PMCID: PMC188898  PMID: 7884874

Abstract

Protection against simian immunodeficiency virus (SIV) challenge was assessed in rhesus monkeys with a vaccine-elicited, single SIV epitope-specific cytotoxic T-lymphocyte (CTL) response in the absence of SIV-specific antibody. Strategies were first explored for eliciting an optimal SIV Gag epitope-specific CTL response. These studies were performed in rhesus monkeys expressing the major histocompatibility complex (MHC) class I gene Mamu-A*01, a haplotype associated with a predominant SIV CTL epitope mapped to residues 182 to 190 of the Gag protein (p11C). We demonstrated that a combined modality immunization strategy using a recombinant Mycobacterium bovis BCG-SIV Gag construct for priming, and peptide formulated in liposome for boosting, elicited a greater p11C-specific CTL response than did a single immunization with peptide-liposome alone. Vaccinated and control monkeys were then challenged with cell-free SIVmne by an intravenous route of inoculation. Despite a vigorous p11C-specific CTL response at the time of virus inoculation, all monkeys became infected with SIV. gag gene sequencing of the virus isolated from these monkeys demonstrated that the established viruses had no mutations in the p11C-coding region. Thus, the preexisting CTL response did not select for a viral variant that might escape T-cell immune recognition. These studies demonstrate that a potent SIV-specific CTL response can be elicited by combining live vector and peptide vaccine modalities. However, a single SIV Gag epitope-specific CTL response in the absence of SIV-specific antibody did not provide protection against a cell-free, intravenous SIV challenge.

Full Text

The Full Text of this article is available as a PDF (270.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benveniste R. E., Roodman S. T., Hill R. W., Knott W. B., Ribas J. L., Lewis M. G., Eddy G. A. Infectivity of titered doses of simian immunodeficiency virus clone E11S inoculated intravenously into rhesus macaques (Macaca mulatta). J Med Primatol. 1994 Feb-May;23(2-3):83–88. doi: 10.1111/j.1600-0684.1994.tb00106.x. [DOI] [PubMed] [Google Scholar]
  2. Chakrabarti L., Guyader M., Alizon M., Daniel M. D., Desrosiers R. C., Tiollais P., Sonigo P. Sequence of simian immunodeficiency virus from macaque and its relationship to other human and simian retroviruses. Nature. 1987 Aug 6;328(6130):543–547. doi: 10.1038/328543a0. [DOI] [PubMed] [Google Scholar]
  3. Chen Z. W., Shen L., Miller M. D., Ghim S. H., Hughes A. L., Letvin N. L. Cytotoxic T lymphocytes do not appear to select for mutations in an immunodominant epitope of simian immunodeficiency virus gag. J Immunol. 1992 Dec 15;149(12):4060–4066. [PubMed] [Google Scholar]
  4. Conley A. J., Kessler J. A., 2nd, Boots L. J., Tung J. S., Arnold B. A., Keller P. M., Shaw A. R., Emini E. A. Neutralization of divergent human immunodeficiency virus type 1 variants and primary isolates by IAM-41-2F5, an anti-gp41 human monoclonal antibody. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3348–3352. doi: 10.1073/pnas.91.8.3348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hu S. L., Abrams K., Barber G. N., Moran P., Zarling J. M., Langlois A. J., Kuller L., Morton W. R., Benveniste R. E. Protection of macaques against SIV infection by subunit vaccines of SIV envelope glycoprotein gp160. Science. 1992 Jan 24;255(5043):456–459. doi: 10.1126/science.1531159. [DOI] [PubMed] [Google Scholar]
  6. Kannagi M., Yetz J. M., Letvin N. L. In vitro growth characteristics of simian T-lymphotropic virus type III. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7053–7057. doi: 10.1073/pnas.82.20.7053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Koup R. A., Safrit J. T., Cao Y., Andrews C. A., McLeod G., Borkowsky W., Farthing C., Ho D. D. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J Virol. 1994 Jul;68(7):4650–4655. doi: 10.1128/jvi.68.7.4650-4655.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Letvin N. L., Daniel M. D., Sehgal P. K., Desrosiers R. C., Hunt R. D., Waldron L. M., MacKey J. J., Schmidt D. K., Chalifoux L. V., King N. W. Induction of AIDS-like disease in macaque monkeys with T-cell tropic retrovirus STLV-III. Science. 1985 Oct 4;230(4721):71–73. doi: 10.1126/science.2412295. [DOI] [PubMed] [Google Scholar]
  9. Letvin N. L. Vaccines against human immunodeficiency virus--progress and prospects. N Engl J Med. 1993 Nov 4;329(19):1400–1405. doi: 10.1056/NEJM199311043291908. [DOI] [PubMed] [Google Scholar]
  10. Miller M. D., Gould-Fogerite S., Shen L., Woods R. M., Koenig S., Mannino R. J., Letvin N. L. Vaccination of rhesus monkeys with synthetic peptide in a fusogenic proteoliposome elicits simian immunodeficiency virus-specific CD8+ cytotoxic T lymphocytes. J Exp Med. 1992 Dec 1;176(6):1739–1744. doi: 10.1084/jem.176.6.1739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Miller M. D., Lord C. I., Stallard V., Mazzara G. P., Letvin N. L. The gag-specific cytotoxic T lymphocytes in rhesus monkeys infected with the simian immunodeficiency virus of macaques. J Immunol. 1990 Jan 1;144(1):122–128. [PubMed] [Google Scholar]
  12. Miller M. D., Yamamoto H., Hughes A. L., Watkins D. I., Letvin N. L. Definition of an epitope and MHC class I molecule recognized by gag-specific cytotoxic T lymphocytes in SIVmac-infected rhesus monkeys. J Immunol. 1991 Jul 1;147(1):320–329. [PubMed] [Google Scholar]
  13. Murphey-Corb M., Martin L. N., Rangan S. R., Baskin G. B., Gormus B. J., Wolf R. H., Andes W. A., West M., Montelaro R. C. Isolation of an HTLV-III-related retrovirus from macaques with simian AIDS and its possible origin in asymptomatic mangabeys. Nature. 1986 May 22;321(6068):435–437. doi: 10.1038/321435a0. [DOI] [PubMed] [Google Scholar]
  14. Pantaleo G., Demarest J. F., Soudeyns H., Graziosi C., Denis F., Adelsberger J. W., Borrow P., Saag M. S., Shaw G. M., Sekaly R. P. Major expansion of CD8+ T cells with a predominant V beta usage during the primary immune response to HIV. Nature. 1994 Aug 11;370(6489):463–467. doi: 10.1038/370463a0. [DOI] [PubMed] [Google Scholar]
  15. Phillips R. E., Rowland-Jones S., Nixon D. F., Gotch F. M., Edwards J. P., Ogunlesi A. O., Elvin J. G., Rothbard J. A., Bangham C. R., Rizza C. R. Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. Nature. 1991 Dec 12;354(6353):453–459. doi: 10.1038/354453a0. [DOI] [PubMed] [Google Scholar]
  16. Reimann K. A., Tenner-Racz K., Racz P., Montefiori D. C., Yasutomi Y., Lin W., Ransil B. J., Letvin N. L. Immunopathogenic events in acute infection of rhesus monkeys with simian immunodeficiency virus of macaques. J Virol. 1994 Apr;68(4):2362–2370. doi: 10.1128/jvi.68.4.2362-2370.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Shen L., Chen Z. W., Miller M. D., Stallard V., Mazzara G. P., Panicali D. L., Letvin N. L. Recombinant virus vaccine-induced SIV-specific CD8+ cytotoxic T lymphocytes. Science. 1991 Apr 19;252(5004):440–443. doi: 10.1126/science.1708168. [DOI] [PubMed] [Google Scholar]
  18. Shen L., Mazzara G. P., DiSciullo S. O., Panicali D. L., Letvin N. L. Immunization with lentivirus-like particles elicits a potent SIV-specific recall cytotoxic T-lymphocyte response in rhesus monkeys. AIDS Res Hum Retroviruses. 1993 Feb;9(2):129–132. doi: 10.1089/aid.1993.9.129. [DOI] [PubMed] [Google Scholar]
  19. Sutjipto S., Pedersen N. C., Miller C. J., Gardner M. B., Hanson C. V., Gettie A., Jennings M., Higgins J., Marx P. A. Inactivated simian immunodeficiency virus vaccine failed to protect rhesus macaques from intravenous or genital mucosal infection but delayed disease in intravenously exposed animals. J Virol. 1990 May;64(5):2290–2297. doi: 10.1128/jvi.64.5.2290-2297.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Townsend A. R., Gotch F. M., Davey J. Cytotoxic T cells recognize fragments of the influenza nucleoprotein. Cell. 1985 Sep;42(2):457–467. doi: 10.1016/0092-8674(85)90103-5. [DOI] [PubMed] [Google Scholar]
  21. Watkins D. I., Kannagi M., Stone M. E., Letvin N. L. Major histocompatibility complex class I molecules of nonhuman primates. Eur J Immunol. 1988 Sep;18(9):1425–1432. doi: 10.1002/eji.1830180919. [DOI] [PubMed] [Google Scholar]
  22. Yamamoto H., Miller M. D., Tsubota H., Watkins D. I., Mazzara G. P., Stallard V., Panicali D. L., Aldovini A., Young R. A., Letvin N. L. Studies of cloned simian immunodeficiency virus-specific T lymphocytes. gag-specific cytotoxic T lymphocytes exhibit a restricted epitope specificity. J Immunol. 1990 May 1;144(9):3385–3391. [PubMed] [Google Scholar]
  23. Yasutomi Y., Koenig S., Haun S. S., Stover C. K., Jackson R. K., Conard P., Conley A. J., Emini E. A., Fuerst T. R., Letvin N. L. Immunization with recombinant BCG-SIV elicits SIV-specific cytotoxic T lymphocytes in rhesus monkeys. J Immunol. 1993 Apr 1;150(7):3101–3107. [PubMed] [Google Scholar]
  24. Yasutomi Y., Palker T. J., Gardner M. B., Haynes B. F., Letvin N. L. Synthetic peptide in mineral oil adjuvant elicits simian immunodeficiency virus-specific CD8+ cytotoxic T lymphocytes in rhesus monkeys. J Immunol. 1993 Nov 1;151(9):5096–5105. [PubMed] [Google Scholar]
  25. Yasutomi Y., Reimann K. A., Lord C. I., Miller M. D., Letvin N. L. Simian immunodeficiency virus-specific CD8+ lymphocyte response in acutely infected rhesus monkeys. J Virol. 1993 Mar;67(3):1707–1711. doi: 10.1128/jvi.67.3.1707-1711.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES