Description of research program: My research is focused on investigating immune mechanisms that control viruses with an emphasis on mucosal and T cell immunity. Our goal is to use that information to develop new vaccines that prevent or treat the associated diseases. My program consists of 4 major areas: 1) Discovery /development of novel therapeutic and prophylactic vaccines for HIV; 2) Define immune mechanisms of viral control in the SIV model for AIDS; 3) Develop a universal vaccine approach for influenza; and 4) Investigate novel vaccine delivery and adjuvant platforms. All 4 programs use nonhuman primates to identify immune mechanisms of viral control using a species that closely resembles humans and as the gold-standard for preclinical evaluation of new vaccines for HIV, influenza, and other vaccines prior to human testing. Our current focus is DNA vaccines as a lead approach for inducing T cell responses and genetic adjuvants expressing enterotoxins or cytokines to enhance mucosal responses. Recent results in our laboratory showed that administration of an adjuvanted therapeutic DNA vaccine to the skin of SIV infected-macaques during ART afforded a durable functional cure (long-term protection from viral rebound after stopping ART) in approximately 50% of the macaques. Ongoing studies in our laboratory aim to determine the immune and virological mechanisms underlying vaccine-induced functional cure. Current efforts in collaboration with other investigators also endeavor to determine the relationship between gene expression and innate responses induced during the earliest stages post SIV mucosal exposure or vaccination, the induction of adaptive immune responses, and mucosal protection or long-term control of SIV. Our influenza studies are focused on developing a vaccine that induces mucosal immunity and T cell responses against sequences conserved in influenza and provides universal protection from genetic drift and shift. Efforts in the influenza program will progress a preclinical vaccine candidate from mice to nonhuman primates as the final translational species to validate lead influenza vaccine candidates prior to human clinical testing.