Immune responses to HIV virus immunization - Project 2

HIV 病毒免疫的免疫反应 - 项目 2

• 批准号: 10198682
• 负责人: Margaret Juliana McElrath
• 金额: $ 59.64万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-19 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10198682
• 关键词: Acquired Immunodeficiency Syndrome; Address; Adjuvant; Anatomy; Antigens; Area; B cell repertoire; B-Lymphocytes; Bioinformatics; Blood; Bone Marrow; CD8-Positive T-Lymphocytes; Cell physiology; Cells; Critical Pathways; Data; Data Set; Epidemic; Evolution; Formulation; Foundations; Funding; Future; Generations; Goals; HIV; HIV Infections; HIV Vaccine Trials Network; HIV immunization; HIV vaccine; HIV-1; Human; Immune; Immune response; Immunity; Immunization; Immunologic Memory; Immunology; Infection; Investigation; Kinetics; Link; Memory; Methods; Molecular Profiling; Outcome; Pathway interactions; Phase; Phenotype; Plasma Cells; Population Heterogeneity; Positioning Attribute; Preventive vaccine; Regimen; Sampling; Series; Source; System; Systems Biology; T-Lymphocyte; Technology; Tissues; United States National Institutes of Health; Vaccination; Vaccine Research; Vaccines; Work; adaptive immune response; analytical method; analytical tool; base; bioinformatics tool; cohort; efficacy trial; first-in-human; improved; infection rate; insight; lymph nodes; malaria infection; neutralizing antibody; novel; phase 1 study; pre-exposure prophylaxis; response; vaccine efficacy; vaccine trial

Pre-exposure prophylaxis and treatment can lower HIV infection rates but nearly two million new infections still occur worldwide each year. A vaccine that can elicit long-lived protective immunity against HIV infection offers the best prospect to end the AIDS epidemic. While no licensed HIV vaccine is available, the modest efficacy observed in the RV144 Thai Trial raises hope that a preventive vaccine is possible. To improve on this efficacy, a deeper understanding of the underlying immune mechanism of vaccine protection is crucial. Our proposed studies aim at generating critical insights on how to improve anti-HIV T cell function, induce enhanced immune potency and durability, and develop paths to elicit broad neutralizing antibodies. We are in a unique position to address these topics with access to an exceptional set of samples from several HIV vaccine trials and well- characterized HIV infection cohorts. Our proposed studies include assessment of the kinetics of the vaccine- induced immune response in relevant anatomic compartments (lymph nodes, bone marrow and gut) and access to cutting edge analytical methods to generate linked datasets that are ideally suited for our proposed, comprehensive systems biology approach. Our project team is uniquely suited to conduct these studies, as leaders and well-established collaborators focused on HIV vaccine research, translational immunology, systems approaches to understand immunological memory, and immune correlates analyses. We expect that our work will reveal testable hypotheses on the underlying mechanistic interplay between key components of the innate and adaptive immune response that are responsible for protection against HIV by vaccination.

暴露前的预防和治疗可以降低艾滋病毒感染率，但仍有近200万新感染者 每年在世界范围内发生。一种可以诱导对艾滋病毒感染产生长期保护性免疫力的疫苗提供了 结束艾滋病流行的最好前景。虽然目前还没有获得许可的艾滋病毒疫苗，但这种温和的疗效 在泰国的RV144试验中观察到的结果提高了人们对预防性疫苗可能的希望。为了提高这一功效， 更深入地了解疫苗保护的潜在免疫机制是至关重要的。我们的建议 研究旨在就如何改善抗HIV T细胞功能、诱导增强免疫 效力和耐用性，并开发诱导广泛中和抗体的途径。我们处于一个独特的位置来 通过访问来自几个艾滋病毒疫苗试验的一组特殊样本来解决这些主题，以及 描述了艾滋病毒感染队列的特征。我们建议的研究包括评估疫苗的动力学- 在相关解剖间隔(淋巴结、骨髓和肠道)和 访问尖端分析方法，以生成非常适合我们建议的、 综合系统生物学方法。我们的项目团队非常适合进行这些研究，因为 领导者和知名合作者专注于艾滋病毒疫苗研究、转化免疫学、 了解免疫记忆和免疫相关分析的系统方法。我们期待着 我们的工作将揭示可检验的假设，即关键组件之间的潜在机制相互作用 负责通过接种疫苗预防艾滋病毒的先天和获得性免疫反应。