HIGHLY EFFECTIVE CONTROL OF AIDS VIRUS CHALLENGE IN MACAQUES

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。 2010年7月（原始病毒攻击后290天），用抗CD 8抗体处理6只先前接种VSV/SFV E660并用SIVsmE 660攻击的恒河猴（Macaca mulatta），以进行体内CD 8耗竭。 完全抵抗感染的四只动物具有在CD 8耗尽后仍然检测不到的血浆病毒载量，这进一步支持了在这些动物中消除免疫力的想法。 在这两只猴中，SIV感染消退的两只动物再次出现病毒感染，峰值病毒载量略高于之前观察到的水平（耗竭后为5.5和6.7 log拷贝/ml，之前为3.9和5.8 log拷贝/ml）。 为了进一步测试最初接种疫苗所提供的保护是否持久，以及免疫系统是否可以在长时间休息后通过额外接种重新激活，将在来年对5只未受最初病毒攻击保护的动物进行重新免疫和重新攻击。 将继续监测所有动物，以跟踪感染或无感染的进展。 此外，在本研究中，我们利用单基因组分析（SGA）技术a）表征SIVsmE 660病毒攻毒贮备液的Env-我们已完成测序并计算了攻毒E660群的贮备液多样性;和B）表征来自接种VSV疫苗并经直肠内攻毒的恒河猴的创始病毒。 目的是比较和对比来自接种VSV-HA疫苗的动物的创始病毒Env序列，这两种动物显示出部分保护-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.