VACCINATION AGAINST INTRAPARTUM HIV-1 CLADE C TRANSMISSION

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。 我们正在使用恒河猴艾滋病毒感染和艾滋病的模型来开发针对世界上最流行的艾滋病毒C分支毒株(HIV-C)的潜在疫苗策略。为了测试针对HIV-C的潜在疫苗的效力，我们开发了混合病毒，称为SHIV，通过将猴子艾滋病病毒的基因成分与HIV的包膜(Env)部分结合起来；我们使用从非洲婴儿分离的两种HIV-C毒株的Env开发了两种这样的病毒。我们开发疫苗的方法是：1)产生基于免疫细胞的对多种病毒成分的反应，以及2)中和基于抗体的对环境病毒的免疫。每一种艾滋病毒毒株的环境病毒都是独一无二的，并模拟了这样的现实，即接种疫苗的人不会接触到与用于疫苗制备的艾滋病毒毒株相同的艾滋病毒毒株。我们故意用SHIV挑战我们接种的猴子，与用于接种疫苗的环境相比，SHIV是不匹配的。在一项研究中，在婴儿时期对多种结构成分的SHV免疫的猴子，通过两种形式的C型SHV显示出对低剂量和高剂量挑战的保护，其中包括一种完全保护的病例。在最近的一项研究中，与对照组相比，同样接种疫苗的猕猴表现出延迟，直到病毒血症和病毒血症高峰出现，并且血浆病毒载量较低；这些疫苗中的三分之一没有病毒血症的证据。 我们还在跟踪一组动物，这些动物以前接种过疫苗和/或接触过C级疫苗，这些动物保持了高水平的广谱中和抗体(NAB)。我们正在分析这些动物的抗体反应的细微特异性，以确定NAB识别的包膜的特定位置，这些位置在不同的艾滋病毒株中是常见的。这些信息对于疫苗成分的设计将是重要的，以提高抗体，在接种疫苗的人中中和广泛的艾滋病毒毒株。

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. We are using a rhesus macaque model of HIV infection and AIDS to develop potential vaccine strategies against the clade C strain of HIV (HIV-C), the world's most prevalent strain. For efficacy testing of potential vaccines against HIV-C, we developed hybrid viruses, called SHIVs, by combining genetic components of a monkey AIDS virus with a portion of HIV called Envelope (Env); we developed two such viruses using Envs from two HIV-C strains isolated from African infants. Our approach to vaccine development is to generate: 1) immune cell-based responses to multiple viral components, and 2) neutralizing antibody-based immunity to Env. The Env of each HIV strain is unique and mimic reality where vaccinated individuals will not be exposed to HIV strains identical to that used for vaccine preparation. We deliberately challenged our vaccinated monkeys with SHIVs that are Env-mismatched compared to the Env used for vaccination. In one study, monkeys immunized as infants against multiple structural components of SHIV showed protection against both low-dose and high-dose challenges with two forms of a clade C SHIV, including one case of complete protection. In a more recent study, similarly vaccinated macaques showed delays until the onset of viremia and peak viremia, and lower plasma viral loads compared with controls; one third of these vaccines had no evidence of viremia. We are also following a set of animals, previously vaccinated and/or exposed to clade C SHIVs that have maintained high levels of broadly-reactive neutralizing antibodies (nAbs). We are analyzing the fine-specificity of the antibody responses in these animals to identify specific sites of envelope recognized by nAbs that are common among different HIV strains. This information will be important for the design of vaccine components to raise antibodies that would neutralize a broad range of HIV strains in vaccinated humans.