Support of the Emory National Primate Research Center

摘要 这一补充的总体目标是开发疫苗策略，诱导强中和抗体 使用mRNA和修饰的安卡拉牛痘（MVA）疫苗递送平台的针对HIV的应答。到 为了解决补充的具体目标，我们将利用在 埃默里国家灵长类动物研究中心（Emory Center for HIV/AIDS Vaccine and Cure Research Consortium） 中心我们建议使用BG 505 MD 39 SOSIP mRNA作为我们的疫苗策略来引发bnAb。我们 假设肌内递送BG 505 MD 39 mRNA为全长gp 160或截短gp 140 将在恒河猴中诱导具有广泛中和活性的HIV特异性中和抗体。 此外，我们想探索异源SIV Gag/Pol mRNA初免和MVA加强对SIV Gag/Pol mRNA表达的影响。 CD 8 T细胞应答，并评估免疫途径如何改变CD 8 T细胞的免疫应答能力。 通过MVA。我们提出两个具体目标。目的1：比较MD 39 gp 160的免疫原性 和gp 140 mRNA IM免疫。在目标2中，我们将描述通过以下途径诱导的免疫应答： 异源mRNA初免和MVA加强，并确定免疫途径是否影响CD 8 T细胞 由MVA引起的反应。通过完成这些目标，我们希望制定更好的疫苗接种策略 可以产生中和抗体和T细胞的抗艾滋病毒药物。

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.