Evaluation of a CCR5 Vaccine for HIV infection in the SIV/Macaque Model

描述（由申请人提供）：在SIV/猕猴模型中评估CCR5疫苗对HIV感染的影响。HIV疫苗的开发因其广泛的抗原变异而变得复杂。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是一种自身蛋白，在HIV的复制、传播和发病过程中起关键作用。通过在病毒样颗粒（vlp）表面高密度展示来自CCR5的肽，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IgG抗体的能力。我们基于vlp的疫苗诱导针对CCR5的高滴度IgG抗体，这些抗体与天然CCR5结合并抑制病毒复制。在本项目中，我们将评估基于vlp的靶向CCR5疫苗抑制猕猴粘膜SIV感染的能力。在目标1中，我们将评估我们的疫苗在肌内和阴道内接种的免疫原性。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。

DESCRIPTION (provided by applicant): Evaluation of a CCR5 Vaccine for HIV Infection in the SIV/Macaque Model. 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 self- protein 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 high- titer 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. PUBLIC HEALTH RELEVANCE: In this project, we will evaluate the ability of a VLP-based vaccine targeting the HIV receptor, CCR5, to prevent SIV infection in macaques.