Scientific Project 2: HIV AIDS Defining molecular signatures in humans following vaccination that can inform pathways to protective immunity against HIV-1 infection

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The overall goal of HIPC3 Project 2 is to identify human molecular signatures induced by HIV-1 vaccines and adjuvant formulations that are of potential relevance to protection against HIV-1 infection in diverse populations. Our proposed investigations will focus on three areas where critical insights are needed: 1) comprehensive assessment and comparison of the quality and enhanced potency and durability of immune responses following immunization with a soluble native-like Env trimer formulated with different adjuvants, 2) evaluation of lymph node germinal cell activities and B cell function and phenotype that have the potential to initiate development of HIV-1 broad neutralizing antibodies, and 3) advance high-throughput systems to interrogate the HIV-specific T cell repertoire following vaccination and identify profiles that may associate with immune protection in partially efficacious vaccine trials. Embedded in these studies will be selected analyses of response signatures in unique tissue sources and in diverse populations. These investigations will accelerate progress toward an effective vaccine by probing innate and adaptive immune responses at an unprecedented level in humans.