RABIES VIRUS-BASED VECTORS AS AN HIV-1 VACCINE

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 评价了高度减毒狂犬病病毒(RV)疫苗载体对高致病性SIVmac251攻击的保护作用。用表达SIVmac239-GagPol的RV、表达SIVmac239-GagPol的RV和表达SIVmac239-GagPol的RV的组合免疫MAMU-A*01阴性恒河猴，或用空RV载体免疫。8周后，动物接受了表达相同抗原的异种RV的加强免疫。在免疫后12周，所有动物均经静脉注射致病SIVmac251-Cx的TCID50。与对照动物相比，两个疫苗组免疫的猕猴的病毒设定点降低了1.31.6倍。GagPol/Env免疫动物的峰值病毒载量也明显较低。与对照组相比，接种疫苗的猕猴在攻击后更快地产生SIVmac251中和抗体和CD8+T细胞对各种SIV表位的反应。此外，接种疫苗的猕猴更好地维持了外周记忆中的CD4+T细胞，并能够在粘膜中建立多功能CD8+T细胞反应。这些发现表明了基于轮状病毒的载体的前景，并对开发有效的艾滋病毒疫苗具有重要意义。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Highly attenuated rabies virus (RV) vaccine vectors were evaluated for their ability to protect against highly pathogenic SIVmac251 challenge. Mamu-A*01 negative rhesus macaques were immunized in groups of four with either: RV expressing SIVmac239-GagPol, a combination of RV expressing SIVmac239-Env and RV expressing SIVmac239-GagPol, or with empty RV vectors. Eight weeks later animals received a booster immunization with a heterologous RV expressing the same antigens. At 12 weeks post-boost, all animals were challenged intravenously with 100 TCID50 of pathogenic SIVmac251-CX. Immunized macaques in both vaccine groups had 1.31.6-log-fold decrease in viral set point compared to control animals. The GagPol/Env immunized animals also had a significantly lower peak viral load. When compared to control animals following challenge, vaccinated macaques had a more rapid induction of SIVmac251 neutralizing antibodies and of CD8+ T cell responses to various SIV epitopes. Moreover, vaccinated macaques better maintained peripheral memory CD4+ T cells and were able to mount a poly-functional CD8+ T cell response in the mucosa. These findings indicate promise for RV-based vectors and have important implications for the development of an efficacious HIV vaccine.