Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
Immunization of rhesus macaques by lipopeptides induces cytolytic T lymphocytes (CTL).
Symp Nonhum Primate Models AIDS. 1992 Nov 17-20;10:abstract no. 112. Unique Identifier : AIDSLINE PRIM10/93200954 Bourgault I; Venet A; Levy JP; ICGM, U 152, Hopital Cochin, Paris, France.
Abstract:
INTRODUCTION: An effective vaccination against HIV/SIV will require the generation of a CTL response in addition to neutralizing antibodies in order to kill early infected cells. After determining that NEF and GAG proteins were highly immunogenic for induction of CTL in SIVmac251-infected macaques (J. Immunol. 1992; 148:2899) we decided to test the ability of lipopeptides to generate cytolytic memory T cells in macaques. METHODS: Twelve rhesus macaques were immunized with a mixture of seven lipopeptides (5 were derived from NEF--aa 101-126, 125-147, 155-178, 201-225, 221-247 and 2 from GAG--aa 165-195, 246-281). Peptides were chosen either because they were CTL targets in SIV-infected macaques (J. Virol. 1992; 66:750) or because they had strong homologies with corresponding CTL epitopic regions in HIV-infected individuals. Immunization was performed monthly during 3 months by subcutaneous injection of the 7 lipopeptides. Effector cell lines were obtained by in vitro stimulation with the pool of peptides in presence of feeder cells. Cytotoxic activity was tested against autologous B immortalized cell lines, sensitized with peptides or infected by recombinant vaccinia viruses expressing the Nef or Gag genes. RESULTS: 1 - CTL were found in 5/12 immunized macaques and were classical CD8+ cells since CD8 depletion abrogated completely the cytolytic activity, whereas CD4 depletion increased the level of lysis. 2 - Five peptides (NEF 125-147, 155-178, 201-225 and GAG 165-195, 246-281) were recognized by different macaques. Only 1 macaque recognized 2 different peptides (NEF 125-147 and 155-178) with the same level of lysis. 3 - Four shorter peptides were defined as epitopes: NEF 125-138, 164-178, 201-215 and GAG 176-195. 4 - In all cases, effector cell lines killed target cells infected with the recombinant vaccinia virus expressing the relevant gene. CONCLUSIONS: Lipopeptidic constructions induce CD8+CTL responses in rhesus macaques. These CTL recognize the immunizing peptide as well as the endogenously processed antigen. These results suggest that memory CTL would be able to kill SIV-infected cells. The potential protection against SIV by these CTL will be tested soon.
Keywords: Animal Antigens, CD8/IMMUNOLOGY Cytotoxicity, Immunologic Epitopes/IMMUNOLOGY Gene Products, gag/*IMMUNOLOGY Gene Products, nef/*IMMUNOLOGY Immunization Macaca mulatta Peptide Fragments/IMMUNOLOGY Simian Acquired Immunodeficiency Syndrome/IMMUNOLOGY SIV/*IMMUNOLOGY T-Lymphocytes, Cytotoxic/*IMMUNOLOGY Vaccines, Synthetic/*IMMUNOLOGY Viral Vaccines/*IMMUNOLOGY ABSTRACT 930630
M9361066
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Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
