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. 1992 Dec 1;176(6):1739–1744. doi: 10.1084/jem.176.6.1739

Vaccination of rhesus monkeys with synthetic peptide in a fusogenic proteoliposome elicits simian immunodeficiency virus-specific CD8+ cytotoxic T lymphocytes

PMCID: PMC2119476  PMID: 1460429

Abstract

An effective vaccine against the human immunodeficiency virus should be capable of eliciting both an antibody and a cytotoxic T lymphocyte (CTL) response. However, when viral proteins and peptides are formulated with traditional immunological adjuvants and inoculated via a route acceptable for use in humans, they have not been successful at eliciting virus-specific, major histocompatibility complex (MHC) class I-restricted CTL. We have designed a novel viral subunit vaccine by encapsulating a previously defined synthetic peptide CTL epitope of the simian immunodeficiency virus (SIV) gag protein within a proteoliposome capable of attaching to and fusing with plasma membranes. Upon fusing, the encapsulated contents of this proteoliposome can enter the MHC class I processing pathway through the cytoplasm. In this report, we show that after a single intramuscular vaccination, rhesus monkeys develop a CD8+ cell-mediated, MHC class I-restricted CTL response that recognizes the synthetic peptide immunogen. The induced CTL also demonstrate antiviral immunity by recognizing SIV gag protein endogenously processed by target cells infected with SIV/vaccinia recombinant virus. These results demonstrate that virus-specific, MHC class I-restricted, CD8+ CTL can be elicited by a safe, nonreplicating viral subunit vaccine in a primate model for acquired immune deficiency syndrome. Moreover, the proteoliposome vaccine formation described can include multiple synthetic peptide epitopes, and, thus, offers a simple means of generating antiviral cell-mediated immunity in a genetically heterogeneous population.

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Selected References

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  1. Carbone F. R., Bevan M. J. Induction of ovalbumin-specific cytotoxic T cells by in vivo peptide immunization. J Exp Med. 1989 Mar 1;169(3):603–612. doi: 10.1084/jem.169.3.603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Collins D. S., Findlay K., Harding C. V. Processing of exogenous liposome-encapsulated antigens in vivo generates class I MHC-restricted T cell responses. J Immunol. 1992 Jun 1;148(11):3336–3341. [PubMed] [Google Scholar]
  3. Deres K., Schild H., Wiesmüller K. H., Jung G., Rammensee H. G. In vivo priming of virus-specific cytotoxic T lymphocytes with synthetic lipopeptide vaccine. Nature. 1989 Nov 30;342(6249):561–564. doi: 10.1038/342561a0. [DOI] [PubMed] [Google Scholar]
  4. Desrosiers R. C., Wyand M. S., Kodama T., Ringler D. J., Arthur L. O., Sehgal P. K., Letvin N. L., King N. W., Daniel M. D. Vaccine protection against simian immunodeficiency virus infection. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6353–6357. doi: 10.1073/pnas.86.16.6353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gething M., Koszinowski U., Waterfield M. Fusion of Sendai virus with the target cell membrane is required for T cell cytotoxicity. Nature. 1978 Aug 17;274(5672):689–691. doi: 10.1038/274689a0. [DOI] [PubMed] [Google Scholar]
  6. Golding H., Shearer G. M., Hillman K., Lucas P., Manischewitz J., Zajac R. A., Clerici M., Gress R. E., Boswell R. N., Golding B. Common epitope in human immunodeficiency virus (HIV) I-GP41 and HLA class II elicits immunosuppressive autoantibodies capable of contributing to immune dysfunction in HIV I-infected individuals. J Clin Invest. 1989 Apr;83(4):1430–1435. doi: 10.1172/JCI114034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Goodman-Snitkoff G., Good M. F., Berzofsky J. A., Mannino R. J. Role of intrastructural/intermolecular help in immunization with peptide-phospholipid complexes. J Immunol. 1991 Jul 15;147(2):410–415. [PubMed] [Google Scholar]
  8. Gould-Fogerite S., Mazurkiewicz J. E., Raska K., Jr, Voelkerding K., Lehman J. M., Mannino R. J. Chimerasome-mediated gene transfer in vitro and in vivo. Gene. 1989 Dec 14;84(2):429–438. doi: 10.1016/0378-1119(89)90517-9. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Mannino R. J., Gould-Fogerite S. Liposome mediated gene transfer. Biotechniques. 1988 Jul-Aug;6(7):682–690. [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. Moore M. W., Carbone F. R., Bevan M. J. Introduction of soluble protein into the class I pathway of antigen processing and presentation. Cell. 1988 Sep 9;54(6):777–785. doi: 10.1016/s0092-8674(88)91043-4. [DOI] [PubMed] [Google Scholar]
  14. Morrison L. A., Lukacher A. E., Braciale V. L., Fan D. P., Braciale T. J. Differences in antigen presentation to MHC class I-and class II-restricted influenza virus-specific cytolytic T lymphocyte clones. J Exp Med. 1986 Apr 1;163(4):903–921. doi: 10.1084/jem.163.4.903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Murphey-Corb M., Martin L. N., Davison-Fairburn B., Montelaro R. C., Miller M., West M., Ohkawa S., Baskin G. B., Zhang J. Y., Putney S. D. A formalin-inactivated whole SIV vaccine confers protection in macaques. Science. 1989 Dec 8;246(4935):1293–1297. doi: 10.1126/science.2555923. [DOI] [PubMed] [Google Scholar]
  16. Nair S., Zhou F., Reddy R., Huang L., Rouse B. T. Soluble proteins delivered to dendritic cells via pH-sensitive liposomes induce primary cytotoxic T lymphocyte responses in vitro. J Exp Med. 1992 Feb 1;175(2):609–612. doi: 10.1084/jem.175.2.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nixon D. F., McMichael A. J. Cytotoxic T-cell recognition of HIV proteins and peptides. AIDS. 1991 Sep;5(9):1049–1059. [PubMed] [Google Scholar]
  18. Osterhaus A., de Vries P., Heeney J. AIDS vaccine developments. Nature. 1992 Feb 20;355(6362):684–685. doi: 10.1038/355684b0. [DOI] [PubMed] [Google Scholar]
  19. Redfield R. R., Wright D. C., James W. D., Jones T. S., Brown C., Burke D. S. Disseminated vaccinia in a military recruit with human immunodeficiency virus (HIV) disease. N Engl J Med. 1987 Mar 12;316(11):673–676. doi: 10.1056/NEJM198703123161106. [DOI] [PubMed] [Google Scholar]
  20. Schulz M., Zinkernagel R. M., Hengartner H. Peptide-induced antiviral protection by cytotoxic T cells. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):991–993. doi: 10.1073/pnas.88.3.991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Shimizu Y., DeMars R. Production of human cells expressing individual transferred HLA-A,-B,-C genes using an HLA-A,-B,-C null human cell line. J Immunol. 1989 May 1;142(9):3320–3328. [PubMed] [Google Scholar]
  23. Takahashi H., Takeshita T., Morein B., Putney S., Germain R. N., Berzofsky J. A. Induction of CD8+ cytotoxic T cells by immunization with purified HIV-1 envelope protein in ISCOMs. Nature. 1990 Apr 26;344(6269):873–875. doi: 10.1038/344873a0. [DOI] [PubMed] [Google Scholar]
  24. Takeda A., Tuazon C. U., Ennis F. A. Antibody-enhanced infection by HIV-1 via Fc receptor-mediated entry. Science. 1988 Oct 28;242(4878):580–583. doi: 10.1126/science.2972065. [DOI] [PubMed] [Google Scholar]
  25. Yewdell J. W., Bennink J. R., Hosaka Y. Cells process exogenous proteins for recognition by cytotoxic T lymphocytes. Science. 1988 Feb 5;239(4840):637–640. doi: 10.1126/science.3257585. [DOI] [PubMed] [Google Scholar]
  26. Zagury D. Anti-HIV cellular immunotherapy in AIDS. Lancet. 1991 Sep 14;338(8768):694–695. doi: 10.1016/0140-6736(91)91269-z. [DOI] [PubMed] [Google Scholar]

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