HIGHLY EFFECTIVE CONTROL OF AIDS VIRUS CHALLENGE IN MACAQUES

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。 2010年7月(原病毒攻击后290天)，用SIVsmE660免疫的6只恒河猴(Macaca Mulatta)接受了抗CD8抗体的体内CD8去除。四只完全抵抗感染的动物的血浆病毒载量在CD8耗尽后仍然检测不到，进一步支持了这些动物的绝育免疫的想法。解决了SIV感染的两只动物的病毒感染卷土重来，峰值病毒载量略高于之前看到的这两只猴子的病毒载量(耗尽后的5.5和6.7个对数拷贝/毫升，而之前的3.9和5.8个对数拷贝/毫升)。为了进一步测试最初接种疫苗所提供的保护是否持久，以及在长时间休息后是否可以通过额外接种疫苗重新激活免疫系统，将在来年对5只免受原始病毒挑战的动物重新接种疫苗并再次挑战。所有动物将继续接受监测，以跟踪感染或缺乏感染的进展情况。 此外，在这项研究中，我们正在利用单基因组分析(SGA)技术来a)表征SIVsmE660病毒挑战种群的Env-我们已经完成了序列测定并计算了挑战E660种群的种群多样性；以及b)表征了VSV疫苗接种和直肠内挑战的恒河猴的创始病毒。目标是比较和对比来自接种VSV-HA疫苗的动物的创始人病毒Env序列，这两种动物显示出部分保护-与VSV-E660-Gag-Env疫苗。这项工作目前正在进行中。

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. Six Rhesus macaques (Macaca mulatta) previously vaccinated with VSV/SFV E660 and challenged with SIVsmE660 were treated with anti-CD8 antibody to perform in vivo CD8 depletions in July 2010 (290 days after the original viral challenge). The four animals that completely resisted infection had plasma virus loads that remained undetectable after CD8 depletion further supporting the idea of sterilizing immunity in these animals. The two animals that resolved their SIV infections had a resurgence of viral infection with peak viral loads slightly higher than those seen previously (5.5 and 6.7 log copies/ml after depletion versus 3.9 and 5.8 log copies/ml previously) in these two monkeys. To further test if the protection afforded by the original vaccination is long lasting and if the immune system can be re-activated with an additional vaccination after a long period of rest, five animals protected from the original viral challenge will be re-immunized and re-challenged in the coming year. All animals will continue to be monitored to follow the progression of infection or lack thereof. Additionally in this study we are utilizing the single genome analysis (SGA) technique to a) to characterize Env of the SIVsmE660 viral challenge stock-we have finished sequencing and calculated the stock diversity of the challenge E660 swarm; and b) to characterize the founder viruses from rhesus macaques vaccinated with VSV vaccines and challenged intra-rectally. The goal is to compare and contrast the founder viruses Env sequences originating from animals vaccinated with VSV-HA vaccine from the two animals that showed partial protection-with VSV-E660-Gag-Env vaccine. This work is currently in progress.