TEMPORAL ANALYSIS OF IMMUNE RESPONSES AND PROTECTION INDUCED BY SIVDELTANEF

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。 以前的研究表明，SIVdeltanef免疫后5周对IV攻击有部分保护作用，而SIVmac251在免疫后15周完全保护IV攻击。这些结果表明，对SIVdeltanef感染后免疫反应个体发育的详细分析应该有助于深入了解保护性免疫的机制。我们对SIVdeltanef诱导的SIV特异性免疫反应的个体发生以及这些反应与SIVmac239预防静脉攻击的相关性进行了全面的分析。在SIVdeltanef感染后2周就检测到相对较高频率的SIV特异性T细胞反应。纵向分析表明，ELISPOT反应在感染后14周大约衰退了三分之一，细胞免疫反应没有明显的扩大。这些动物在感染后5周和15周静脉注射SIVmac239，在所有动物中都显示出明显的无菌保护，未接种疫苗的对照组没有检测到野生型血浆病毒血症，预计病毒载量会很高。对整个蛋白质组ELISPOT反应和四聚体反应的分析表明，无论是在5周还是15周后，接种疫苗的动物都没有证据表明记忆性CD8阳性T细胞反应。这些数据表明，SIVmac239对同源保护的保护早在SIVdeltanef感染后5周就可以发生，之前观察到的针对SIVmac251的保护成熟似乎与SIV特异性CD8阳性T细胞反应的数量变化无关。

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.