Multi-Omics Analysis of Broadly Neutralizing Antibodies and Therapeutic Vaccination

广泛中和抗体和治疗性疫苗的多组学分析

• 批准号: 10724219
• 负责人: Dan H. Barouch
• 金额: $ 141.27万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-11 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10724219
• 关键词: Basic Science; Biological; Biological Assay; Cellular Immunity; Computer Analysis; Data Set; Development; Goals; HIV-1; Human; Immune; Immune response; Immunologics; Intervention Studies; Lymphoid Tissue; Macaca mulatta; Mediating; Mucous Membrane; Pathway interactions; Peripheral; Program Research Project Grants; Research; SIV; Sampling Studies; Testing; Tissues; Treatment Efficacy; Vaccine Therapy; Vaccines; Viral; Viral reservoir; animal resource; anti-viral efficacy; antiretroviral therapy; antiviral immunity; combinatorial; data integration; gastrointestinal; improved; lymph nodes; multiple omics; neutralizing antibody; next generation; nonhuman primate; programs; simian human immunodeficiency virus; therapeutic vaccine; vaccination strategy; vaccine efficacy; viral rebound

SUMMARY The goal of this P01 program is to define mechanisms of efficacy of broadly neutralizing antibodies (bNAbs) and therapeutic vaccines for HIV-1 in a highly collaborative and multifaceted research program. Our overall hypothesis is that immunologic strategies for HIV-1 cure delay viral rebound both by targeting the viral reservoir and by increasing host antiviral immunity. We will evaluate mechanisms of therapeutic efficacy in both humans and nonhuman primates (NHPs) using coordinated virologic, immunologic, and multi-omic approaches with the goal of developing improved next generation HIV-1 cure strategies. We will apply cutting- edge, high-throughput, multi-omic profiling platforms and integrate these data sets to generate a comprehensive tissue landscape and regulatory network of the viral reservoir and host immune responses. This program builds on our existing studies over the past several years in both humans and NHPs evaluating the ability of bNAbs and therapeutic vaccines to delay viral rebound following discontinuation of antiretroviral therapy (ART). We will first utilize existing samples from these studies to generate hypotheses regarding correlates of delayed viral rebound. We will then perform new interventional studies in NHPs with spatial multi- omic analyses in lymph nodes and gastrointestinal mucosal tissues to test hypotheses in order to define mechanisms of reservoir targeting by bNAbs and therapeutic vaccines. The significance of this program is the potential to define the biologic pathways that lead to delayed viral rebound following ART discontinuation. An improved understanding of partially effective bNAbs and therapeutic vaccines in humans and NHPs will lead to basic research advances that will allow the development of improved next generation HIV-1 cure approaches. To accomplish the goals of this P01 program, we propose the following Projects and Cores: Project 1. Multi-Omics Correlates of Broadly Neutralizing Antibody Efficacy Project 2. Multi-Omics Correlates of Therapeutic Vaccine Efficacy Core A. Administrative Core Core B. Multi-Omics Core Core C. Computational Analysis Core Core D. NHP Core

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