Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery

HIV/艾滋病疫苗免疫学和免疫原发现中心

• 批准号: 8681328
• 负责人: Barton F. Haynes
• 金额: $ 2990.73万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-15 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8681328
• 关键词: AIDS/HIV problem; Active Immunization; Address; Agreement; Antibodies; Antibody Formation; Antigens; Automobile Driving; B-Lymphocytes; CD4 Positive T Lymphocytes; CD8B1 gene; Cells; Clinical Trials; Collaborations; Cryoelectron Microscopy; Crystallography; Development; Epitopes; Goals; Grant; HIV; HIV Vaccine Trials Network; HIV-1; Human; Immune response; Immune system; Immunity; Immunologics; Immunology; Infection prevention; Knowledge; Laboratories; Leadership; Location; Macaca mulatta; Major Histocompatibility Complex; Memory; Military Personnel; NIH Vaccine Research Center; Natural Killer Cells; Passive Immunization; Pathway interactions; Preventive; Principal Investigator; Research; Research Personnel; Research Project Grants; Research Support; Sampling Studies; Site; Structure; T cell response; T-Lymphocyte; Technology; Time; Universities; Vaccinated; Vaccine Design; Vaccines; Variant; Work; base; design; efficacy trial; experience; improved; killings; neutralizing antibody; novel; operation; particle; prevent; programs; response; tool; transmission process; vaccine candidate; vaccine efficacy

DESCRIPTION (provided by applicant): The Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) will be a new consortium established to undertake immunologic research directed at tackling major scientific problems that hinder the development of an effective HIV-1 vaccine. Over the next 7 years, the CHAVI-ID will build on the progress made by the CHAVI consortium and apply state-of-the-art technologies and both immunologic and virologic tools to improve rational HIV-1 vaccine design. Our vaccine strategy will be based on identifying and targeting novel HIV-1 vulnerabilities to B, T and NK cell immune responses and then using this information to design vaccines that will induce protective immunity at the time and location of HIV-1 transmission. The overall CHAVI-ID goals are to design immunogens that prevent HI V-1 transmission by inducing innate, antibody as well as CD4+ and CD8+ T cell responses at the site of HIV-1 entry. Since the components of the human immune system work in concert, the final goal of the CHAVI-ID is to design a practical preventive HIV-1 vaccine that incorporates protective innate, antibody and T cell-targeted immunogens. CHAVI-ID will be led by the CHAVI-ID principal investigator and scientific leadership group along with CHAVI-ID leaders of 11 Scientific Research Support Components and an experienced Operations and Management Support Component. The centerpiece of our CHAVI-ID research agenda is the Research Program which has three Foci: 1. Induction of Protective Antibody Responses, 2. Induction of Protective T Cell Responses and 3. Induction of Protective Innate Responses-all of which are derived directly from discoveries made during the past 6 years of the Center for HIV/AIDS Vaccine Immunology (CHAVI) grant, and together constitute a clear path to overcoming the remaining obstacles preventing development of an effective preventive vaccine. CHAVI-ID Organization: The CHAVI-ID will be a component of the Global HIV-1 Enterprise comprised of outstanding investigators using state-of-the art technology that will address critical gaps in scientific knowledge through focused, coordinated studies ultimately targeted at making a successful HlV-1 vaccine. CHAVI-ID will initially work to identify innate, T, and B cell protectie immune responses by studying samples obtained from completed human vaccine efficacy trials, and by carrying out passive and active immunization trials to prevent infections by R5 SHIVs in rhesus macaques. CHAVI-ID investigators will define structures of protective HIV-1 envelope (Env) epitopes using crystallography and single particle cryoelectron microscopy, design vaccine strategies for driving antibody maturation pathways of difficult-to-induce neutralizing antibodies, as well as.design vaccine strategies for expanding the breadth and depth of induced T cell responses. CHAVl-ID will have an administrative structure that facilitates eliminating unsuccessful programs and acquiring new expertise as they are needed. CHAVI-ID studies of protective immune responses in vaccinees will be supported by long-term and ongoing research agreements and collaborations with the HIV Vaccine Trials Network (HVTN), the NIH Vaccine Research Center (VRC) and the Military HIV Research Program (MHRP). CHAVI-ID will be led by the CHAVI-ID principal investigator and scientific leadership group along with CHAVl-lD leaders of 12 Scientific Research Support Components (SRSCs) (Table 1). The CHAVI Principal Investigator (PI) is Barton Haynes at Duke University. He has chosen five leaders to join the CHAVI Scientific Leadership Group (SLG): Garnett Kelsoe from Duke University, Bette Korber from Los Alamos National Laboratory, Norman Letvin from Harvard University, Andrew McMichael from Oxford University and Joseph Sodroski from Harvard University. RELEVANCE: Much progress has been made over the past 6 years in overcoming roadblocks to development of a safe and effective HIV-1 vaccine. However, a number of roadblocks remain. By study of immune responses made by HIV-1 clinical trial vaccinees in a modestly successful HIV-1 vaccine trial (RV144), and by study of HIV-1-infected people who eventually make the desired immune responses, a path to overcoming the final roadblocks can be charted, and improved vaccine candidates designed for new clinical trials. OVERALL UM-1 CENTER APPLICATION:

描述（由申请人提供）：HIV/AIDS 疫苗免疫学和免疫原发现中心 (CHAVI-ID) 将是一个新的联盟，旨在开展免疫学研究，旨在解决阻碍有效 HIV-1 疫苗开发的重大科学问题。在接下来的7年里，CHAVI-ID将在CHAVI联盟所取得的进展的基础上继续发展，并应用最先进的技术以及免疫学和病毒学工具来改进合理的HIV-1疫苗设计。我们的疫苗策略将基于识别和针对 B、T 和 NK 细胞免疫反应的新型 HIV-1 脆弱性，然后利用这些信息设计疫苗，在 HIV-1 传播的时间和地点诱导保护性免疫。 CHAVI-ID 的总体目标是设计免疫原，通过在 HIV-1 进入位点诱导先天抗体以及 CD4+ 和 CD8+ T 细胞反应来预防 HIV-1 传播。由于人类免疫系统的各个组成部分协同工作，CHAVI-ID 的最终目标是设计一种实用的预防性 HIV-1 疫苗，其中结合了保护性先天免疫原、抗体和 T 细胞靶向免疫原。 CHAVI-ID 将由 CHAVI-ID 首席研究员和科学领导小组以及 11 个科学研究支持部门的 CHAVI-ID 领导者和经验丰富的运营团队领导 和管理支持组件。我们 CHAVI-ID 研究议程的核心是研究计划，该计划具有三个重点：1. 保护性抗体反应的诱导，2. 保护性 T 细胞反应的诱导和 3. 保护性先天反应的诱导 - 所有这些都直接源自HIV/艾滋病疫苗免疫学中心 (CHAVI) 资助的过去 6 年中取得的发现共同构成了克服阻碍开发有效预防性疫苗的剩余障碍的明确途径。 CHAVI-ID 组织：CHAVI-ID 将成为全球 HIV-1 事业的一部分，由杰出的研究人员组成，使用最先进的技术，解决关键问题 通过集中、协调的研究来弥补科学知识上的差距，最终目标是成功研制出 HIV-1 疫苗。 CHAVI-ID 最初将通过研究从已完成的人类疫苗功效试验中获得的样本，并通过进行被动和主动免疫试验来预防恒河猴中 R5 SHIV 的感染，来识别先天、T 和 B 细胞保护性免疫反应。 CHAVI-ID 研究人员将使用晶体学和单粒子冷冻电子显微镜定义保护性 HIV-1 包膜 (Env) 表位的结构，设计用于驱动难以诱导的中和抗体的抗体成熟途径的疫苗策略，以及设计疫苗策略扩大诱导 T 细胞反应的广度和深度。 CHAVl-ID 将拥有一个管理结构，有助于消除不成功的项目并根据需要获取新的专业知识。 CHAVI-ID 对疫苗接种者保护性免疫反应的研究将得到与 HIV 疫苗试验网络 (HVTN)、NIH 疫苗研究中心 (VRC) 和军事 HIV 研究计划 (MHRP) 的长期持续研究协议和合作的支持。 CHAVI-ID 将由 CHAVI-ID 首席研究员和科学领导小组以及 CHAV1-ID 12 个科学研究支持部门 (SRSC) 的领导者领导（表 1）。 CHAVI 首席研究员 (PI) 是杜克大学的 Barton Haynes。他选出了五位领导者加入 CHAVI 科学领导小组（SLG）：杜克大学的 Garnett Kelsoe、洛斯阿拉莫斯国家实验室的 Bette Korber、哈佛大学的 Norman Letvin、牛津大学的 Andrew McMichael 和哈佛大学的 Joseph Sodroski。 相关性：过去 6 年在克服开发安全有效的 HIV-1 疫苗的障碍方面取得了很大进展。然而，仍然存在一些障碍。通过对 HIV-1 临床试验疫苗接种者在一项取得一定成功的 HIV-1 疫苗试验 (RV144) 中做出的免疫反应的研究，以及对最终做出所需免疫反应的 HIV-1 感染者的研究，找到了克服最终结果的途径。可以绘制障碍图，并为新的临床试验设计改进的候选疫苗。 UM-1 中心总体申请：