PROTECTION AGAINST VAGINAL CHALLENGE IN SIVDELTANEF-VACCINATED ANIMALS

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。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 缺乏关于防止艾滋病毒/SIV感染的保护机制的信息仍然是开发安全有效的艾滋病疫苗的主要障碍之一。 用减毒SIV毒株接种猕猴一直被证明是诱导保护免受致病性SIV攻击的最有效手段，并提供了最佳可用实验模型来定义负责保护的特定机制。 我们小组以前的研究提供了证据表明，SIV特异性CD 8阳性T细胞和体液应答都有助于SIVdeltanef诱导的保护性免疫，但尚未能够评估它们的相对重要性或新的适应性或先天性免疫应答对保护的潜在贡献。 本研究的目的是利用一些新的技术进行全面分析的作用，适应性和先天性免疫反应介导的保护由SIV诱导nef对阴道挑战，艾滋病毒传播的最重要的方式之一。SIVnef感染导致感染后前2-5周内自然杀伤细胞、SIV特异性CD 8阳性T细胞应答和抗体应答显著增加;这些应答与接种后5周时对阴道SIVmac 251攻击的最小保护相关。 体液和细胞免疫应答均显示出在疫苗接种后5至20周成熟的渐进性证据，这与针对阴道SIVmac 251攻击的实质性（尽管仍不完全）保护有关。 这些研究结果产生了对慢病毒感染的保护性免疫的特征的全面描述。

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. Lack of information on mechanisms of protection against HIV/SIV infection remains one of the leading obstacles to the development of a safe and effective AIDS vaccine. Vaccination of macaques with attenuated SIV strains has consistently proved to be the most effective means of inducing protection against pathogenic SIV challenge and offers the best available experimental model to define specific mechanisms responsible for protection. Previous studies from our group have provided evidence that SIV-specific CD8-positive T cell and humoral responses both contribute to protective immunity induced by SIVdeltanef but have not been able to assess their relative importance or the potential contributions of novel adaptive or innate immune responses to protection. The goal of this study is to utilize a number of novel techniques to carry out a comprehensive analysis of the role of adaptive and innate immune responses in mediating protection induced by SIVnef against vaginal challenge, one of the most important modes of HIV transmission. SIVnef infection resulted in significant increases in natural killer cells, SIV-specific CD8-positive T cell responses and antibody responses in the first 2-5 weeks after infection; these responses were associated with minimal protection against vaginal SIVmac251 challenge at 5 weeks after vaccination. Both humoral and cellular immune responses display progressive evidence of maturation from 5 to 20 weeks after vaccination, associated with substantial, though still incomplete, protection against vaginal SIVmac251 challenge. These studies results are yielding a comprehensive delineation of the signature characteristics of protective immunity against lentiviral infection.