COMPARISON OF VACCINE REGIMENS: HIV-SIV RECOMBINANTS WITH PROTEIN BOOSTING

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。 最初，我们试图比较两种M. mulatta和 M.以确定天然病毒蛋白达特单独是否可在任一或两种动物模型中赋予保护作用。尽管在其他研究中，具有免疫原性的、无活性的达特未引起对病毒攻击的保护;因此，确定活性（天然）分子是否可用于疫苗设计是重要的。 第二，我们想要确定用编码达特的腺病毒重组体替代免疫，然后进行2次达特蛋白免疫（组II）是否与单独的多次达特蛋白免疫（组I）一样有效。 疫苗以尽可能少的免疫接种赋予保护性免疫的能力是重要的，尤其是在发展中国家。 第三，我们试图评价两种免疫原联合使用（均旨在阻断初始感染或早期病毒复制事件）减弱急性期病毒血症的能力（第III组）。 免疫原为HIV Env和达特。 最后，细胞免疫应答，特别是对SIV Gag蛋白的应答，已经显示出能够显著降低SHIV攻击模型中慢性期的病毒血症。因此，用gag蛋白免疫（第IV组）动物。 与适当的对照组一起，这些免疫方案有助于阐明和比较免疫期间和病毒攻毒后免疫活性病毒基因产物的应答和保护效力。

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. Originally we sought to compare the same immunization protocol in both M. mulatta and M. fascicularis to determine if native viral protein, Tat alone could confer protection in either or both animal models. Although immunogenic, inactive Tat had not elicited protection against viral challenge in other studies; therefore it was important to determine if the active (native) molecule would be useful in vaccine design. Second, we wanted to determine if substitution of immunizations with Adenovirus recombinants encoding Tat followed by 2 Tat protein immunizations (Group II) is as effective as the multiple Tat protein immunization alone ( Group I). The ability of a vaccine to confer protective immunity with as few immunizations as possible is important, especially in the developing world. Third, we sought to evaluate two immunogens in combination, both aimed at blocking initial infection or early virus replication events, for their ability to blunt acute phase viremia (Group III). The immunogens were HIV Env and tat. Finally, cellular immune responses, especially to the SIV Gag protein, had been shown able to significantly reduce viremia in the chronic phase in the SHIV challenge model. Therefore, (Group IV) animals were immunized with gag protein. Together with appropriate control groups, these immunization regimens were to help elucidate and compare the response and protective efficacy of immunologically active viral gene products during immunization and after virus challenge.