EVALUATION OF A CCR5 VACCINE FOR HIV INFECTION IN THE SIV/MACAQUE MODEL

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 由于广泛的抗原变异，艾滋病毒疫苗的开发变得复杂 由HIV显示。作为针对病毒的替代方案，我们已经开发了针对CCR5的疫苗，CCR5是一种在HIV复制、传播和致病过程中至关重要的自身蛋白。通过在病毒样颗粒(VLP)表面高密度展示来自CCR5的多肽，我们已经证明，我们可以有效地克服B细胞耐受机制，这种机制通常限制了诱导针对自身蛋白的高滴度抗体的能力。我们的基于VLP的疫苗诱导针对CCR5的高滴度抗体，这些抗体与天然的CCR5结合并抑制病毒复制。 在本项目中，我们将评估针对CCR5的VLP疫苗抑制猕猴黏膜SIV感染的能力。在目标1中，我们将评估我们的疫苗在肌肉和阴道内接种时的免疫原性。在目标2中，我们将通过阴道挑战方案挑战恒河猴，并评估疫苗接种所提供的保护。这些研究将使我们能够评估针对CCR5的疫苗预防艾滋病毒感染的潜力。

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. HIV vaccine development has been complicated by the extensive antigenic variation displayed by HIV. As an alternative to targeting the virus, we have developed vaccines targeting CCR5, a selfprotein that is critically involved in HIV replication, transmission, and pathogenesis. By displaying peptides derived from CCR5 at high density on the surface of virus-like particles (VLPs), we have shown that we can efficiently overcome the mechanisms of B cell tolerance that normally limit the ability to induce high-titer IgG antibodies against self-proteins. Our VLP-based vaccines induce hightiter IgG antibodies against CCR5, these antibodies bind to native CCR5 and inhibit viral replication. In this project, we will evaluate the ability of a VLP-based vaccine targeting CCR5 to inhibit mucosal SIV infection of macaques. In Aim 1 we will evaluate the immunogenicity of our vaccines upon intramuscular and intravaginal inoculation. In Aim 2 we will challenge rhesus macaques via a vaginal challenge protocol and assess the protection provided by vaccination. These studies will allow us to assess the potential of vaccines targeting CCR5 to protect against HIV infection.