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

在 SIV/猕猴模型中评估 CCR5 疫苗对 HIV 感染的影响

• 批准号: 8357323
• 负责人: Bryce C Chackerian
• 金额: $ 14.36万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357323
• 关键词: Antibodies; Antigenic Variation; B-Lymphocytes; Binding; CCR5 gene; California; Evaluation; Funding; Grant; HIV; HIV Infections; HIV vaccine; Immunoglobulin G; Infection; Intramuscular; Macaca; Macaca mulatta; Modeling; National Center for Research Resources; Pathogenesis; Peptides; Primates; Principal Investigator; Proteins; Protocols documentation; Research; Research Infrastructure; Resources; SIV; Source; Surface; United States National Institutes of Health; Vaccination; Vaccines; Vagina; Viral; Virus; Virus-like particle; base; cost; density; immunogenicity; transmission process; vaccine development

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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 HIV疫苗的开发因广泛的抗原变异而变得复杂 由艾滋病毒展示。作为靶向病毒的替代方法，我们开发了靶向CCR5的疫苗，CCR5是一种与HIV复制，传播和发病机理有关的自我蛋白质。通过在病毒样颗粒表面（VLP）表面显示源自CCR5的肽，我们已经表明，我们可以有效克服B细胞耐受性的机制，通常限制诱导抗蛋白质抗体的高效率IgG抗体的能力。我们基于VLP的疫苗诱导Hightiter IgG抗体针对CCR5，这些抗体与天然CCR5结合并抑制病毒复制。 在该项目中，我们将评估靶向CCR5靶向CCR5抑制猕猴粘膜SIV感染的能力。在AIM 1中，我们将在肌内接种和内部接种后评估疫苗的免疫原性。在AIM 2中，我们将通过阴道挑战方案来挑战恒河猕猴，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预防HIV感染的疫苗的潜力。