Support of the Emory National Primate Research Center

摘要 这一补充的总体目标是开发能够诱导强中和抗体的疫苗策略。 使用信使核糖核酸和改良的安卡拉牛痘(MVA)疫苗交付平台应对艾滋病毒。至 为了达到补充材料的具体目标，我们将利用从 埃默里国家灵长类动物研究中心艾滋病毒/艾滋病疫苗和治疗研究联盟 中心。我们建议使用BG505 MD39 SOSIP mRNA作为我们的疫苗策略来诱导bNAbs。我们 假设BG505 MD39 mRNA以全长gp160或截短gp140的形式肌肉内传递 将在恒河猴体内诱导具有广泛中和活性的HIV特异性中和抗体。 此外，我们还想探讨异源SIV gag/Pol信使核糖核酸和MVA Boost对 CD8 T细胞的反应，并评估免疫途径如何改变CD8 T细胞成为 在MVA的推动下。我们提出了两个具体目标。在目标1中，我们将比较MD39 gp160的免疫原性。 和gp140 m RNA肌注免疫。在目标2中，我们将描述通过以下途径诱导的免疫反应 异源信使核糖核酸和MVA增强免疫途径是否影响CD8 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HIV病毒。

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.