HARNESSING INNATE IMMUNITY TO ENHANCE T-CELL INDUCING HIV VACCINES

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。 该项目是盖茨基金会赞助的一个大型艾滋病疫苗开发财团的一部分。 整个项目旨在确定在疫苗接种期间触发先天免疫系统的各种要素对随后针对疫苗的适应性免疫应答，特别是T细胞应答的影响。 Picker博士正在监督该项目的非人类灵长类动物部分，该项目有以下目标：1）制定方案，将掺入SIV或HIV基因产物的选定疫苗[蛋白质+佐剂或微生物载体]应用于猴群，2）选择适当的研究动物，3）对这些猴实施这些方案，4）为研究猴提供临床护理/监测，5）从猴受试者收集样品，6）将这些样品分配到适当的测试实验室进行分析，7）确定局部、引流淋巴结和远端部位全身和粘膜中的免疫诱导的免疫应答的动力学，8）评估由疫苗接种方案产生的T细胞应答的质量和数量，和9）确定免疫应答的效力。 研究疫苗接种方案。 在该项目主持下的工作已经鉴定了TLR 3和RIG-1激动剂poly I：C作为引发Ab和T细胞对SIV蛋白的应答的上级佐剂。 目前，我们正在进行一项大规模的聚I：C佐剂化SIVenv蛋白的有效性试验，以提供抗SIVenv抗体应答，该抗体应答将防止在重复限制剂量直肠内攻击后获得高致病性SIV。

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. This project is part of a large consortium on AIDS vaccine development sponsored by the Gates Foundation. The overall project is designed to determine the effects that triggering various elements of the innate immune system during vaccination has on the subsequent adaptive immune response against the vaccine, particularly the T cell response. Dr. Picker is supervising the nonhuman primate component of this project, which has the following goals: 1) development of protocols to apply selected vaccines [protein + adjuvant(s) or microbial vectors] incorporating SIV or HIV gene products to monkey cohorts, 2) selection of appropriate study animals, 3) implementation of these protocols with these monkeys, 4) provision of clinical care/monitoring for study monkeys, 5) collection of samples from monkey subjects, 6) distribution of these samples to the appropriate testing laboratories for analysis, 7) determination of the kinetics of the adjuvant-induced immune response locally, in draining lymph nodes, and distal sites systemically and mucosally, 8) assessment of the quality and quantity of T cell responses generated by the vaccination protocols, and 9) determination of the efficacy of the vaccination protocols to be studied. Work under the auspices of this project has identified the TLR3 and RIG-I agonist poly I:C as a superior adjuvant for eliciting both Ab and T cell responses to SIV proteins. Currently, we are performing a large efficacy trial of poly I:C adjuvanted SIVenv protein to provide anti-SIVenv antibody responses that would prevent acquisition of highly pathogenic SIV after repeated limiting dose intra-rectal challenge.