Nonhuman primate scientific research support component

非人灵长类科学研究支持部分

• 批准号: 9517669
• 负责人: SAMPA SANTRA
• 金额: $ 40.75万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9517669
• 关键词: Adjuvant; Antibodies; Antigens; Area; Biological Models; CD8-Positive T-Lymphocytes; Complement; Development; Effectiveness; Evolution; Goals; HIV vaccine; HIV-1; HIV-1 vaccine; Immune; Immune response; Immune system; Immunization; Immunize; Immunology; Macaca; Macaca mulatta; Modeling; Monoclonal Antibodies; Mucous Membrane; Recombinants; Research Personnel; Research Support; SIV; Specificity; System; Technology; Vaccinated; Vaccines; Work; env Gene Products; immunogenicity; in vivo; nonhuman primate; novel; novel strategies; prevent; programs; simian human immunodeficiency virus; vaccine development

The goal of the Nonhuman Primate Support Component is to support the overall program of the CHAVI-ID by performing in vivo passive protection or enhancement studies to characterize the functional activities of mAbs generated by CHAVI-ID investigators, by performing immunization studies with novel immunogens developed by CHAVI investigators, and performing correlative mAb and immune functional studies to use the rhesus monkey as a model to accelerate HlV-1 vaccine development. This work will be facilitated by recent advances we have made in a number of complementing areas, including the development of novel mucosal SIV/SHIV challenge models, novel SHIV constructs expressing transmitted/founder HlV-1 envelopes, adjuvants that substantially increase the immunogenicity of HlV-1 envelope protein immunogens, and recombinant technology for generating monoclonal antibodies from immunized rhesus macaques. Specific Aims Aim 1. Pursue passive protection studies in rhesus macaques to determine the effectiveness of antibodies with defined specificities and CD8 T cell-produced factors in blocking SHIV/SIV mucosal acquisition. Aim 2. Perform immunization studies in rhesus macaques to explore novel strategies for vaccine induction of antibodies that might protect against HIV-1 acquisition. Aim 3. Explore the evolution of broadly neutralizing anti-HIV-1 antibodies in vaccinated rhesus macaques.

非人灵长类动物支持组件的目标是通过进行体内被动保护或增强研究以表征CHAVI-ID研究者生成的mAb的功能活性，通过使用CHAVI研究者开发的新型免疫原进行免疫研究，并进行相关的单克隆抗体和免疫功能研究，以恒河猴为模型加速HIV-1疫苗的研制。我们在许多补充领域取得的最新进展将促进这项工作，包括开发新的粘膜SIV/SHIV攻击模型、表达传递/建立者HIV-1包膜的新的SHIV构建体、显著增加HIV-1包膜蛋白免疫原的免疫原性的佐剂和用于从免疫的恒河猴产生单克隆抗体的重组技术。 具体目标 目标1。在恒河猴中进行被动保护研究，以确定具有特定特异性的抗体和CD 8 T细胞产生的因子在阻断SHIV/SIV粘膜获得中的有效性。 目标2.在恒河猴中进行免疫研究，以探索疫苗诱导抗体的新策略，这些抗体可能防止HIV-1感染。 目标3。探索广泛中和抗HIV-1抗体在接种疫苗的恒河猴中的演变。