Support of the Emory National Primate Research Center

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Abstract The overall goal of this supplement is to develop vaccine strategies that induce strong neutralizing antibody response against HIV using mRNA and modified vaccinia Ankara (MVA) vaccine delivery platforms. To address the specific goals of the supplement, we will utilize samples obtained from studies conducted in the Emory Center for HIV/AIDS Vaccine and Cure Research consortium at the Emory National Primate Research Center. We propose to use the BG505 MD39 SOSIP mRNA as our vaccine strategy to elicit bnAbs. We hypothesize that BG505 MD39 mRNA delivered intramuscularly as either full length gp160 or truncated gp140 will induce HIV specific neutralizing antibodies with broad neutralization activity in rhesus macaques. Additionally, we would like to explore the effect of heterologous SIV Gag/Pol mRNA prime and MVA boost on the CD8 T cell response and evaluate how the route of immunization alters the ability of CD8 T cells to be boosted by MVA. We propose two specific aims. In Aim 1, we will compare the immunogenicity of MD39 gp160 and gp140 mRNA IM immunization. In Aim 2, we will characterize the immune response induced through heterologous mRNA prime and MVA boost and determine if the route of immunization effects the CD8 T cell response elicited by MVA. By completion of these aims we hope to develop improved vaccination strategy against HIV that can generate both neutralizing antibodies and T cells.