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HIV感染率，但仍有近200万个新感染 每年在全球发生。一种可以引起对HIV感染的长期保护性免疫的疫苗 结束艾滋病流行的最佳前景。虽然没有许可的艾滋病毒疫苗，但适度的功效 在RV144泰国试验中观察到，希望预防疫苗可以进行。为了提高这种功效， 对疫苗保护的潜在免疫机制有更深入的了解至关重要。我们提出的 研究旨在产生有关如何改善抗HIV T细胞功能的关键见解，诱导免疫力增强 效力和耐用性，并发展出引起广泛中和抗体的途径。我们处于独特的位置 通过访问来自几项HIV疫苗试验的一组特殊样本，解决这些主题 艾滋病毒感染队列的特征。我们提出的研究包括评估疫苗的动力学 相关解剖区室（淋巴结，骨髓和肠道）中诱导的免疫反应， 访问尖端分析方法以生成链接的数据集，这些数据集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 领导者和成熟的合作者专注于HIV疫苗研究，转化免疫学，， 系统方法了解免疫记忆并免疫相关。我们期望这一点 我们的工作将在关键组成部分之间的基本机械相互作用上揭示可检验的假设 由疫苗接种来保护HIV的先天和适应性免疫反应。