COMBINING MICROBICIDES AND VACCINES TO PREVENT HIV TRANSMISSION

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。 由于没有有效的疫苗或杀微生物剂来预防艾滋病毒的传播，我们目前正在研究综合战略，以了解这些方法之间存在的协同作用。 使用靶向gp 41的融合抑制剂肽T-1249作为杀微生物剂臂，rAd 26初免、rAd 5 HVR 48加强作为疫苗臂，SIVmac 251作为阴道攻击病毒的初始研究（“高剂量”，经炔雌醇处理的猕猴模型）证明，在组合臂中比单独的疫苗或杀微生物剂臂具有更好的保护。 然而，此后我们使用CMPD 167和ad 5疫苗进行了第二次研究，并用SIVmac 251阴道攻击动物，没有看到显著差异。 事实上，该研究被3/8只对照动物没有被感染的事实所混淆，但该结果也使我们检查了CMPD 167和其他融合抑制剂的敏感性，并且我们发现与我们在先前研究中使用的SHIV 162 P3/4相比，SIVmac对CCR 5融合抑制剂的敏感性存在对数差异。 我们现在正在使用马拉韦罗重复这项实验，并将用SHIV 162 P3挑战以克服这一障碍，同时继续研究SIV和SIV易感性的差异。

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. Since neither an effective vaccine or microbicide to prevent HIV transmission exist, we are currently examining combination strategies to see synergy exists between these approaches. Initial studies using the gp41-targeted fusion inhibitor peptide T-1249 as the microbicide arm, with an rAd26 prime, rAd5HVR48 boost as the vaccine arm and SIVmac251 as the vaginal challenge virus ("high-dose", progesterone-treated macaque model) demonstrated better protection in the combination arm than vaccine or microbicide arms alone. We have however since performed a second study using CMPD167 and the ad5 vaccine and challenged animals vaginally with SIVmac251 and did not see a significant difference. In fact the study was confounded by the fact that 3/8 control animals did not get infected but this result also made us check the susceptibilities of CMPD167 and other fusion inhibitors and we discovered there is a log difference in susceptibility of SIVmac to CCR5 fusion inhibitors compared to the SHIV162P3/4 we have used in prior studies. We are now repeating this experiment using maraviroc, and will challenge with SHIV162P3 to overcome this obstacle while continuing to investigate the differences in susceptibility of SIV and SHIV.