HIGHLY EFFECTIVE CONTROL OF AIDS VIRUS CHALLENGE IN MACAQUES

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。 在过去的研究中，将表达Shiv Env、Gab和Pol蛋白的减毒水泡性口炎病毒(VSV)载体与表达相同Shiv蛋白的改良安卡拉牛痘(MVA)载体的Prime-Boost方案进行了比较。这种方法使用一个不相关的载体(MVA)来增强SIV免疫。在用SHIV89.6P攻击后，MVA增强的动物的峰值攻击病毒载量控制在2×106拷贝/毫升以下，显著低于VSV增强的动物，也低于其他采用相同挑战的疫苗研究报告。MVA增强的动物表现出良好的CD4+T细胞保存，而VSV增强的4只动物中有2只表现出显著的CD4+T细胞丢失。在MVA增强的动物中，增强的保护与攻击前CD8+T细胞对SHV抗原的更强反应以及攻击后更强的SHIV中和抗体产生相关。 我们正在继续监测5只动物，这些动物接种了VSV/VSV或VSV/MVA疫苗，并在2002年接种了SHIV89.6P(VSV-4)。所有动物的病毒载量都低于可检测到的限度。这些动物每季度都会被放血，以遵守持续了5年多的保护措施。 VSV-6是一项使用所有恒河猴A01*+的研究。A01*是SIVmac感染的控制基因。VSV载体免疫的MamuA01+动物与对照组相比病毒载量较低。 新的研究(VSV-7)已经将载体系统从基于SIVmac251的系统转变为SIVE660疫苗和挑战系统。E660系统的优点是，这种SIVsm毒株对中和抗体部分敏感，类似于HIV-1。

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. In past studies the effectiveness of a prime-boost protocol using attenuated vesicular stomatitis virus (VSV) vectors expressing SHIV Env, Gab , and Pol proteins was compared to a VSV vector prime followed with a single boost with modified vaccinia Ankara (MVA) expressing the same SHIV proteins. This approach used an unrelated vector (MVA) to boost SHIV immunity. After challenge with SHIV89.6P, MVA- boosted animals controlled peak challenge viral loads to less than 2x106 copies/ml, significantly lower than in VSV-boosted animals, and lower than reported in other vaccine studies employing the same challenge. MVA-boosted animals have shown excellent preservation of CD4+T cells while 2 of 4 VSV-boosted animals showed significant loss of CD4+T cells. The improved protection in MVA-boosted animals correlates with stronger pre-challenge CD8+T cell responses to SHIV antigens and with stronger post-challenge SHIV neutralizing antibody production. We are continuing monitoring five animals that were given either VSV/VSV or VSV/MVA vaccines and challenged with SHIV89.6p in 2002 (VSV-4). All animals have had viral loads below detectable limits. These animals are being bled quarterly to follow protection which has persisted for over 5 years. VSV-6 is a study using all mamu A01* + rhesus macaques. The A01* is a controller gene for SIVmac infection. VSV-vector immunized MamuA01+ animals had lower virus loads compared to controls. New studies (VSV-7) have shifted the vector system from SIVmac251 based system to a SIVE660 vaccine and challenge system. The advantage of the E660 systems is that this strain of SIVsm is partially sensitive to neutralizing antibody, similar to HIV-1.