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利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：利用SIV减毒活疫苗为研究有效的抗免疫缺陷病毒免疫应答提供一个独特的机会。 2009年春季，我们用SIV减毒株SIVmac239nef接种了8只恒河猴。我们使用各种检测方法监测了该队列中SIV特异性免疫反应的发展。接种疫苗的动物和8个幼稚的对照组一起接受直肠内挑战(ir.)2009年秋天，使用重复、低剂量的未克隆“群体”病毒SIVsmE660。令人惊讶的是，接种疫苗的猕猴显著推迟了SIVsmE660的获得。在用SIVsmE660的6x106 vRNA拷贝进行五次黏膜攻击后，我们在八只接种疫苗的动物中只有四只检测到了挑战毒株的复制。相比之下，在这五次挑战之后，8只对照动物中有7只感染了SIVsmE660。重要的是，感染SIVsmE660疫苗的动物控制了急性病毒复制的高峰期，明显好于幼稚对照组。四名疫苗接种者中有三名在感染后第四周迅速控制了病毒复制。这些结果表明，一种设计良好的艾滋病毒疫苗可能会降低感染的获得率，并在感染的急性期控制病毒复制。 这项研究使用了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.