TEMPORAL ANALYSIS OF IMMUNE RESPONSES AND PROTECTION INDUCED BY SIVDELTANEF

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。子项目和 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。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 先前的研究已经证明，用SIVdeltanef免疫导致在免疫后5周时针对用SIVmac 251的IV攻击的部分保护，但到15周时完全保护。 这些结果表明，SIVdeltanef感染后的免疫反应的个体发育的详细分析，应提供保护性免疫的机制的见解。 我们对SIVdeltanef诱导的SIV特异性免疫应答的个体发生以及这些应答与SIVmac 239静脉内攻击保护的相关性进行了全面分析。 早在SIVdeltanef感染后2周就检测到相对高频率的SIV特异性T细胞应答。 纵向分析表明ELISPOT反应在感染后14周衰减了约三分之一，细胞免疫反应没有明显的扩大。 在感染后5周和15周用静脉内剂量的SIVmac 239攻击这些动物，在所有动物中显示明显的无菌保护，在未接种疫苗的对照中没有可检测到的野生型血浆病毒血症和预期的高病毒载量。 全蛋白质组ELISPOT应答和四聚体应答的分析显示，在5周或15周攻毒后，接种疫苗的动物中没有记忆性CD 8阳性T细胞应答的证据。 这些数据表明，针对SIVmac 239的同源保护的保护可以早在SIVdeltanef感染后5周发生，并且先前观察到的针对SIVmac 251的保护的成熟似乎与SIV特异性CD 8阳性T细胞应答的定量变化无关。

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. Previous studies have demonstrated that immunization with SIVdeltanef results in partial protection against IV challenge with SIVmac251 at 5 weeks after immunization but complete protection by 15 weeks. These results suggest that detailed analysis of the ontogeny of immune responses after infection with SIVdeltanef should offer insights into the mechanisms of protective immunity. We undertook a comprehensive analysis of the ontogeny of SIV-specific immune responses induced by SIVdeltanef and the correlation of these responses to protection against intravenous challenge with SIVmac239. Relatively high frequency SIV-specific T cell responses were detected as early as 2 weeks after SIVdeltanef infection. Longitudinal analysis demonstrated ELISPOT responses had decayed by approximately one-third 14 weeks after infection, with no apparent broadening of the cellular immune response. Challenge of these animals with an intravenous dose of SIVmac239 at 5 and 15 weeks after infection revealed apparently sterile protection in all animals, with no wild-type plasma viremia detectable and expected high viral loads in unvaccinated controls. Analysis of whole proteome ELISPOT responses and tetramer responses revealed no evidence of anamnestic CD8-positive T cell responses in vaccinated animals following challenge at either 5 or 15 weeks. These data demonstrate that protection against homologous protection with SIVmac239 can occur as early as 5 weeks after SIVdeltanef infection and that the previously observed maturation of protection against SIVmac251 does not appear to correlate with quantitative changes in SIV-specific CD8-positive T cell responses.