The availability of an efficient vaccine for the prevention of human AIDS disease is of crucial importance for the future. Today, we lack a precise delineation of which element of immune response is protective against AIDS (humoral or cell-mediated or both) and which antigen (structural, regulatory viral proteins or viral antigens exposed by infected cells) can elicit such protective immune response. The development of an animal system to define these parameters is consequently of crucial need. The comparison of the human and simian immunodeficiency viruses genomes, ultrastructures and pathology strongly suggests that the use the Simian Virus (SIV) - macaques model could be very instructive to elucidate the parameters of a protective AIDs vaccine. This project is devoted to the development of this model. Our contribution to this proposal will be the obtention, by cloning in eucaryotic expression vectors, of viral antigens from SIV. Several antigen formulations (live vaccinia recombinants, purified recombinant proteins produced in yeast and higher eukaryotic cells and inserted in liposomes, ISCOMS or colloidomes) will be obtained. Particular attention will be addressed to the envelope proteins: highly immunogenic antigens will be obtained by mutations in accordance with results of immunization trials using the wild type envelope antigens. The immunogenicity of denatured env products with respect to induction of group-specific neutralizing antibodies will be studied. One of the important steps in the infection process, the induction of membrane fusion, will also be investigated. We intend to analyze the role of syncytia induction by SIV in pathogenesis and the role of cell to cell spread of SIV in resistance of the virus to the immune reaction of the host. The objective of this project is to obtain safe and efficient vaccine preparations by presenting SIV antigens or antigenic determinants in their native configuration.
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