Vaccine induction of SIVmac GAG-specific cytotoxic T lymphocytes in rhesus monkeys.

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Vaccine induction of SIVmac GAG-specific cytotoxic T lymphocytes in rhesus monkeys.

Symp Nonhum Primate Models AIDS. 1993 Sep 19-22;11:abstract no. 10. Unique Identifier : AIDSLINE PRIM11/94191602
Letvin NL; Harvard Medical School, New England Regional Primate Research; Center, Southborough, MA 01772.

Abstract: In view of the importance of cell-associated virus in AIDS virus transmission, an HIV vaccine should be able to induce a virus-specific cytotoxic T lymphocyte (CTL) response. We have employed the SIVmac/rhesus monkey model to explore approaches to vaccine induction of CD8+, major histocompatibility complex (MHC) class I-restricted AIDS virus-specific CTL. In particular, we have made use of the observation that SIVmac-infected rhesus monkeys that express the MHC class I gene product Mamu-A*01 develop SIVmac gag-specific CTL responses with an epitope specificity limited to a single nine amino acid fragment of the gag protein spanning residues 182-190. Since MHC class I presentation of peptide antigen in general occurs only for proteins synthesized and processed intracellularly, strategies for vaccine induction of virus-specific CTL have relied on the use of attenuated viruses or recombinant live organisms as vectors for expression of viral proteins. Accordingly, we have recently shown that live recombinant vaccinia and BCG can elicit SIVmac gag-specific CTL in monkeys. Recent studies have indicated that antigen can enter the MHC class I presentation pathway if introduced intracellularly directly into the cytoplasm, bypassing endosomal/lysosomal degradation. In fact, we have shown that SIVmac gag peptide, delivered formulated either with a proteoliposome or mineral oil adjuvant, can also elicit SIVmac gag-specific CTL. Recent studies have indicated that combined modality immunizations, employing a live vector for priming and peptide boosting, elicit potent CTL, with a higher effector frequency than either approach alone.

Keywords: Animal Antigens, CD8/IMMUNOLOGY Drug Carriers Gene Products, gag/*IMMUNOLOGY Genes, MHC Class I Histocompatibility Antigens Class I/IMMUNOLOGY Liposomes Macaca mulatta Mycobacterium bovis/IMMUNOLOGY Proteolipids SIV/*IMMUNOLOGY T-Lymphocyte Subsets/IMMUNOLOGY T-Lymphocytes, Cytotoxic/DRUG EFFECTS/*IMMUNOLOGY Vaccines, Attenuated/*PHARMACOLOGY Viral Vaccines/*PHARMACOLOGY ABSTRACT
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M9470916

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