Abstract:
The nature of what would constitute a protective immune response in HIV-1, HIV-2 or experimental SIV infection is unclear and therefore the protective components of a putative vaccine are not known. High levels of virus specific MHC restricted cytotoxic T lymphocytes (CTL) are seen early in infection and during the asymptomatic phase of disease and apparently they play an important part in the eradication of the virus. In order that cell associated virus may be cleared, an effective vaccine will almost certainly have to elicit CTL and this may be why attenuated live vaccine which would be expected to elicit cell mediated responses confers protection against SIV challenge in macaques. If subunit vaccines are to be used to elicit CTL it is necessary to identify antigenic epitopes in different proteins in SIV which will stimulate CTL. Such peptides or the proteins from which they are derived can then be included in a vaccine. We are using a strategy which we call 'Reverse Immunogenetics' to identify as many CTL epitopes from SIV as possible in infected and vaccinated cynomolgus macaques. This strategy has previously been used to identify CTL epitopes in HIV-2 and malaria. Thus we have cloned and sequenced three MaFa class I molecules and transfected them into CIR cells and mutant T2 cells which lack transporter genes. Using the CIR transfectants we have been able to elute endogenous peptides and identify predicted motifs for peptides that bind to individual molecules. Using the T2 transfectants we can perform assembly assays with peptides from any SIV protein containing the predicted motifs. Thus we are able to predict which peptides may be recognised by CTL of certain MaFa MHC types and to test these predictions using CTL from vaccinated or infected animals.
Keywords: Animal Antigens, Viral/*ANALYSIS Epitopes/ANALYSIS Immunogenetics/METHODS Macaca fascicularis Major Histocompatibility Complex Simian Acquired Immunodeficiency Syndrome/*IMMUNOLOGY T-Lymphocytes, Cytotoxic/*IMMUNOLOGY/MICROBIOLOGY Viral Vaccines/IMMUNOLOGY ABSTRACT 940730
M9470905
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