PRE-CLINICAL IMMUNOGENICITY STUDIES OF CHIMPANZEE ADENOVIRUS VECTORS

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。 由于我们对艾滋病毒感染期间免疫保护相关性的知识不完全，有效艾滋病疫苗的产生非常复杂。本项目主要研究基于黑猩猩腺病毒（AdC）的候选艾滋病疫苗的免疫原性和对SIV攻击的保护作用。在过去的一年里，我们总结了分析，并发表了使用AdC 7-gDSIVgag（一种表达Gag作为免疫刺激HSV-1gD分子内融合蛋白的载体）加强的AdC 6SIVgag载体进行免疫和攻击研究的结果。此外，我们在表达SIVgag/达特的AdC载体AdC 6和AdC 7的两种组合的安全性、免疫原性和对致病性SIV攻击的保护的另外的大规模研究中取得了显著进展，我们在30个RM（即，AdC 6-SIVgag/达特，然后是AdC 7-SIVgag/达特和AdC 7-SIVgag/达特，然后是AdC 6-SIVgag/达特）。我们已经完成了免疫接种阶段，现在正处于实验的激发阶段，其中包括多达15次低剂量的SIVmac 251直肠内激发，每两周给药一次，每周监测SIV病毒血症。目前，30个RM中有28个已被感染，因此我们预计将在下个月内完成挑战阶段。此时，将在感染后对动物进行另外6个月的随访，以监测它们的疾病进展水平（即，设定点病毒载量、CD 4耗竭、存活）。最终，我们希望这项研究将使我们能够评估表达gag/达特的基于AdC的候选艾滋病疫苗在SIV NHP模型中的功效

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. The generation of an effective AIDS vaccine is greatly complicated by our incomplete knowledge of the correlates of immune protection during HIV infection. This project focuses on the immunogenicity and protection from SIV challenge conferred by chimpanzee adenovirus (AdC)-based candidate AIDS vaccines. Over the past year we concluded the analysis and published the results of an immunization and challenge study using an AdC6SIVgag vector boosted with AdC7-gDSIVgag (a vector expressing Gag as a fusion protein within the immunostimulatoryHSV-1gD molecule). In addition, we made significant progress on an additional large study of the safety, immunogenicity and protection from pathogenic SIV challenge of two combinations of the SIVgag/tat expressing AdC vectors, AdC6 and AdC7, that we used in a sequential heterologous prime-boost regimen in 30 RMs (i.e., AdC6-SIVgag/tat followed by AdC7-SIVgag/tat and AdC7-SIVgag/tat followed by AdC6-SIVgag/tat). We have completed the immunization phase, and we are now in the challenge phase of the experiment, which involves up to 15 low-dose intra-rectal challenges with SIVmac251 that were administered every two weeks with weekly monitoring of SIV viremia. Currently 28 out of 30 RMs have been infected, and thus we expect to complete the challenge phase within the next month. At that point the animals will be followed for an additional 6 months after infection to monitor their level of disease progression (i.e., set point viral load, CD4 depletion, survival). Ultimately we hope that this study will allow us to assess the efficacy in the SIV NHP model of gag/tat expressing AdC-based candidate AIDS vaccines