De Novo Induction of Simian CTL Using Lentivirus Vectors

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DESCRIPTION: (Provided by Applicant) HIV vaccines must be directed at eliciting strong virus specific T-cell responses in order to control HIV-infected cells before the development of fulminant virus production. For any candidate vaccine for HIV, the principal targets must be dendritic cells, since they play a central role in the presentation of antigens to naive T-cells and the induction of primary cellular immune responses. Lentivirus vectors capable of stably integrating and expressing a desired gene in primary nonproliferating cells are potential vaccine delivery systems for dendritic cells. We will determine whether dendritic cells, made to stably express lentivirus gene products with lentivirus vectors, efficiently elicit protective anti-viral immune responses. Toward this objective, we will use the rhesus macaque as an animal model for our vaccine studies. Initially, we will optimize the conditions necessary for the lentivirus vectors to stably express SIV genes in monocyte-derived dendritic cells from rhesus macaques. We will evaluate whether dendritic cells transduced with SIV genes migrate to draining lymphoid tissues, thereby increasing their likelihood of interacting with SIV-specific cytotoxic T-lymphocyte (CTL) precursors. We will determine next if rhesus macaques injected with the transduced cells generate anti-SIV CTL in vivo. Finally, we will investigate if the immunity generated by the transduced dendritic cells in animals provides protection against challenge with infectious SIV. Results from these primate studies will provide important information in developing target vaccines against HIV.