"Characterization of the Immune and Viral Response to a Therapeutic Conserved Elements DNA Vaccine"
Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. The Fuller lab has previously shown that in SIV infected rhesus macaques undergoing antiretroviral therapy (ART), a therapeutic DNA vaccine could prevent progression to AIDS in ~50% of animals after discontinuing ART. However, the likely problem with the previous approach is the inclusion of variable epitopes, mutations in these results in a small loss of viral fitness. We propose to investigate a novel conserved elements (CE) therapeutic DNA vaccine to direct cytotoxic T cells against viral regions that are highly conserved and where mutations induced by 8immune pressure will impose the most deleterious impact on viral fitness. Animals will be infected with SIV and then put on highly active antiretroviral therapy (HAART), during that time they will be vaccinated and following the last vaccination HAART will be discontinued. I hypothesize that the CE therapeutic DNA vaccine will be more effective in preventing animals from progressing to AIDS after stopping HAART and reducing viral fitness versus a traditional immunogen. I will accomplish this goal by combining techniques in molecular biology, virology and immunology to address basic questions in our understanding of vaccine science. This project will provide insights into the virological and immunological profile of a functional of compete cure and advance a novel concept for curing HIV infections.