RABIES VIRUS-BASED VECTORS AS AN HIV-1 VACCINE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 评价高度减毒的狂犬病病毒（RV）疫苗载体针对高致病性SIVmac 251攻击的保护能力。 将Mamu-A*01阴性恒河猴以四只一组用以下任一种免疫：表达SIVmac 239-GagPol的RV、表达SIVmac 239-Env的RV和表达SIVmac 239-GagPol的RV的组合，或用空RV载体。8周后，动物接受表达相同抗原的异源RV的加强免疫。在加强后12周，所有动物用100 TCID 50致病性SIVmac 251-CX静脉内攻击。两个疫苗组的免疫猕猴均具有1.3与对照动物相比，病毒设定点降低1.6对数值。 GagPol/Env免疫的动物也具有显著较低的峰值病毒载量。当与攻击后的对照动物相比时，接种疫苗的猕猴具有SIVmac 251中和抗体和针对各种SIV表位的CD 8 + T细胞应答的更快诱导。此外，接种疫苗的猕猴更好地维持外周记忆CD 4 + T细胞，并能够在粘膜中建立多功能CD 8 + T细胞应答。这些发现表明RV为基础的载体的承诺，并具有重要的意义，有效的艾滋病毒疫苗的发展。

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.