IMMUNOGENICITY AND PROTECTION OF LIVE ATTENUATED SIV239 DELTA NEF IN RHESUS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目的：利用SIV减毒活疫苗研究有效的抗免疫缺陷病毒免疫应答。 用SIV弱毒株SIVmac 239免疫8只恒河猴，2009年春， 我们使用多种检测方法监测了该队列中SIV特异性免疫应答的发展。 将接种的动物沿着8只未处理对照动物经直肠内（i.r.）在2009年秋天，反复使用低剂量的未克隆的“蜂群”病毒SIVsmE 660。令人惊讶的是，接种疫苗的猕猴显著延迟了SIVsmE 660的获得。 在用6 × 106 vRNA拷贝的SIVsmE 660进行5次粘膜攻击后，我们在8只接种动物中仅4只中检测到攻击菌株的复制。 相比之下，8只对照动物中有7只在这5次攻击后感染SIVsmE 660。 重要的是，SIVsmE 660感染的接种动物对急性病毒复制峰值的控制显著优于未感染对照。 四名接种者中有三名在感染后第4周迅速控制了病毒复制。 这些结果表明，设计良好的艾滋病毒疫苗可能会降低感染急性期的获得率并控制病毒复制。 该研究使用WNPRC免疫遗传学和病毒学服务。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To use live-attenuated SIV vaccines as a unique opportunity to study effective anti-immunodeficiency virus immune responses. We vaccinated 8 rhesus macaques with the live-attenuated SIV strain SIVmac239nef in the spring of 2009. We monitored the development of SIV-specific immune responses in this cohort using a variety of assays. The vaccinated animals, along with eight naive controls, were challenged intrarectally (i.r.) with repeated, low doses of the uncloned "swarm" virus SIVsmE660 in the fall of 2009. Surprisingly, vaccinated macaques significantly delayed acquisition of SIVsmE660. After five mucosal challenges with 6x106 vRNA copies of SIVsmE660 we detected replication of the challenge strain in only four of the eight vaccinated animals. In contrast, 7 of the 8 control animals became infected with SIVsmE660 after these five challenges. Importantly, the SIVsmE660-infected vaccinated animals controlled peak acute virus replication significantly better than the naive controls. Three of the four vaccinees rapidly brought virus replication under control by week 4 post-infection. These results suggest that a well-designed HIV vaccine might both reduce the rate of acquisition and control viral replication during the acute phase of infection. The research uses WNPRC Immunogenetics & Virology Services.