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）：艾滋病毒/艾滋病疫苗免疫学和免疫原（CHAVI-ID）的中心将是一个新的财团，旨在进行旨在解决有效HIV-1疫苗发展的主要科学问题的免疫研究。在接下来的7年中，Chavi-ID将基于Chavi联盟所取得的进展，并采用最先进的技术以及免疫学和病毒学工具来改善合理的HIV-1疫苗设计。我们的疫苗策略将基于识别和靶向对B，T和NK细胞免疫反应的新型HIV-1脆弱性，然后使用此信息来设计疫苗，以在HIV-1传播的时间和位置诱导保护性免疫。总体CHAVI-ID目标是设计通过诱导HIV-1进入部位的先天，抗体以及CD4+和CD8+ T细胞反应来防止HI V-1传播的免疫原子。由于人类免疫系统的组成部分共同起作用，因此CHAVI-ID的最终目标是设计一种实用的预防性HIV-1疫苗，该疫苗结合了保护性先天，抗体和T细胞靶向的免疫原子。 Chavi-ID将由Chavi-ID首席研究员和科学领导力小组领导 和管理支持组件。 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开发有效的预防疫苗。 Chavi-ID组织：Chavi-ID将是全球HIV-1企业的组成部分，该企业由杰出的调查员使用最先进的技术组成，该技术将解决关键 通过重点，协调的研究最终旨在成功进行HLV-1疫苗，科学知识的差距。 Chavi-ID最初将通过研究从完整的人类疫苗功效试验中获得的样品，并进行被动和主动免疫试验，以防止R5 SHIV在Rhesus Macaques中进行R5 SHIV感染，从而确定先天，T和B细胞保护免疫反应。 CHAVI-ID研究人员将使用晶体学和单个颗粒冷冻电子显微镜，设计抗体成熟途径的设计疫苗策略来定义保护性HIV-1包膜（ENK）表位的结构，这些疫苗策略难以诱导难以诱导中和抗体中和抗体。 Chavl-ID将具有一种行政结构，可促进消除未成功的计划并根据需要获得新的专业知识。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）（MHRP）的长期和持续合作，将支持有关疫苗保护性免疫反应的CHAVI-ID研究。 Chavi-ID将由Chavi-ID的首席研究员和科学领导小组以及12个科学研究支持组件（SRSC）的Chavl-LD领导者领导（表1）。 Chavi首席研究员（PI）是杜克大学的Barton Haynes。他选择了五名领导人加入Chavi科学领导力小组（SLG）：杜克大学的Garnett Kelsoe，来自哈佛大学的哈佛大学诺曼·莱特文（Norman Letvin），牛津大学的安德鲁·麦克梅尔（Andrew McMichael）的洛斯·阿拉莫斯国家实验室的贝特·科伯（Bette Korber）和哈佛大学的约瑟夫·索德罗斯基（Joseph Sodroski）。 相关性：在过去的6年中，在克服安全有效的HIV-1疫苗的开发方面取得了很多进展。但是，仍然存在许多障碍。通过研究HIV-1临床试验疫苗在适度成功的HIV-1疫苗试验（RV144）中做出的免疫反应，以及通过研究最终使HIV-1感染的人最终导致所需的免疫反应，这是克服最终障碍的途径，可以绘制出最终的疫苗，并改善了为新的临床培训候选人候选人。 整体UM-1中心应用：