It is clear that lentiviral replication in vivo, is partially controlled by the host immune response. Pilot clinical studiers early after infection have suggested that manipulation of the host immune response in the context of active anti-therapy (HAART) may result in an improved ability of the host to control viral replication and delay or stop disease progression. These observations have given rise to the hypothesis that boosting of the host response may be a strategy to improve clinical outcome. In the context of chronic infection in particular it is likely that therapeutic vaccination is highly relevant. This project will test the hypothesis that the cellular immune response can be engineered in the context of SIV infection and HAART. Furthermore that the improved immune response may impact on viral replication and disease course in a chronic infection model system. We will first examine basic principles of DNA immunization that have directed relationship to the SIV therapy studies proposed. We will then test the ability of enhanced DNA vaccines as immune therapy in the primate model. The ability of this approach to modulate anti-viral immune responses, viral load or disease progression. Studiers will involve collaboration with Dr. Mark Lewis at Southern Research Institute for the primate studies, Dr. Siliciano (Project 4) for analysis of viral reservoirs, Dr. Sekaly for tetramer analysis of Class II immune responses (Project 3) & Dr. Letvin (Harvard) & Dr. Boyer (Core B) for analysis of immune responses.
