Administrative Core

行政核心

• 批准号: 8278036
• 负责人: WILLIAM C OLSON
• 金额: $ 14.25万
• 依托单位: PROGENICS PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2011-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8278036
• 关键词: Address; Antibodies; Antigens; Area; Award; Budgets; Characteristics; Cleaved cell; Communities; Crystallography; Data; Disulfides; Ensure; Foundations; Generations; Genetic; Goals; Grant; HIV; HIV Envelope Protein gp120; HIV vaccine; HIV-1; Immune response; Immunology; Immunosuppressive Agents; Industry; Institution; Intellectual Property; Leadership; Manuscripts; Methods; Nature; Peer Review; Policies; Population; Predisposition; Preventive; Production; Property; Reagent; Research; Research Personnel; Research Project Grants; Resolution; Resources; Role; Source; Structure; Technology; Testing; Vaccine Design; Vaccines; Variant; Virion; Virus; base; design; experience; immunogenic; immunogenicity; innovation; meetings; member; monomer; neutralizing antibody; pathogen; programs; success; symposium

Seeinstructions): This HIVRAD program builds upon our recent successes in generating stable, proteolytically mature gp140 trimers (SOSIP gp140s) that mimic virion-associated envelope (Env) in topology and antigenicity. The overall goals of this HIVRAD program are reflected in three major milestones: 1) determine the structure of cleaved Env trimers at <4A resolution, 2) demonstrate methods to overcome HIV-1 Env's immunosuppressive properties, and 3) identify a SOSIP trimer vaccine that elicits heterologous neutralization of diverse HIV-1 isolates. Core A will be responsible for the overall scientific leadership of the HIVRAD. In addition, Core A will coordinate the highly inter-dependent and interactive studies to be performed in Project 1 (HIV-1 Env Vaccine Design, Dr. Moore) and Project 2 (HIV-1 Env Trimer Crystallography, Dr. Wilson) with technical support from Core B (Trimer Production and Immunogenicity Testing, Dr. Olson). Core A will provide a broad range of management support necessary to meet the goals of the HIVRAD program. The key functions of Core A can be grouped according to three Specific Aims: 1) Provide overall scientific direction and coordination for the program; 2) Facilitate sharing of research data and resources within the program and with the broader scientific community; and 3) Provide statistical, fiscal, administrative and intellectual property support. These Aims will be accomplished by an existing team of professionals with significant industry experience in each of the functional areas. The Core activities are central to the overall success of the HIVRAD program. Core A will facilitate the timely exchange of materials, data and other information between Project 1, Project 2 and additional collaborators. The interactive nature of the program necessitates that information and materials generated in the program be exchanged in a timely fashion with the participating members of the HIVRAD, and Core A will responsible for ensuring timely interactions between the HIVRAD Projects and Cores in order to optimally advance the program. In addition, Core A will establish and annually convene an external Scientific Advisory Group to assist with decisions on the direction of the research program. The overall role of Core A is to optimally coordinate, direct and facilitate the research of Project 1 and Project 2 in order to achieve our shared goal of providing a fundamental advance towards an HIV-1 vaccine. RELEVANCE (Seeinstructions): Nearly 1% of the world's population is infected with HIV, and a preventive vaccine is urgently needed. Most efficacious vaccines elicit antibodies that can neutralize the pathogen, but current-generation HIV vaccines are not effective in this regard. Obstacles include our limited understanding of the structure and immunology of HIV-1 envelope trimers. This HIVRAD represents an innovative approach to addressing these challenges in order to provide a fundamental advance in our ability to elicit HIV-neutralizing antibodies with a vaccine.

参见说明）： 该 HIVRAD 计划建立在我们最近在产生稳定的、蛋白水解成熟的 gp140 三聚体 (SOSIP gp140s) 在拓扑结构和抗原性方面模仿病毒粒子相关包膜 (Env)。 HIVRAD 计划的总体目标体现在三个主要里程碑上：1) 确定 切割的 Env 三聚体的结构，分辨率 <4A，2) 展示了克服 HIV-1 Env 的方法 免疫抑制特性，3) 鉴定出可引发异源中和的 SOSIP 三聚体疫苗 不同的 HIV-1 分离株。核心 A 将负责 HIVRAD 的整体科学领导。在 此外，核心A将协调在以下领域进行的高度相互依赖和互动的研究： 项目 1（HIV-1 包膜疫苗设计，Moore 博士）和项目 2（HIV-1 包膜三聚体晶体学，Moore 博士） Wilson），并得到 Core B（三聚体生产和免疫原性测试，Olson 博士）的技术支持。 核心 A 将提供实现 HIVRAD 目标所需的广泛管理支持 程序。核心 A 的关键功能可根据三个具体目标进行分组： 1) 提供整体 项目的科学指导和协调； 2）促进研究数据和资源共享 在该计划内以及更广泛的科学界； 3) 提供统计、财政、 行政和知识产权支持。这些目标将由现有的团队来实现 在每个职能领域具有丰富行业经验的专业人员。核心活动是 HIVRAD 计划的整体成功至关重要。 核心A将促进项目1、 项目 2 和其他合作者。程序的交互性质需要信息 项目中产生的材料和材料应及时与参与成员交换 HIVRAD 和核心 A 将负责确保 HIVRAD 项目之间的及时互动 和核心，以最佳地推进该计划。此外，Core A 将每年建立 召集外部科学顾问小组协助决定研究方向 程序。核心 A 的总体作用是优化协调、指导和促进项目的研究 1 和项目 2，以实现我们的共同目标，即为 HIV-1 提供根本性进展 疫苗。 相关性（参见说明）： 全球近1%的人口感染艾滋病毒，迫切需要预防性疫苗。最多 有效的疫苗会产生可以中和病原体的抗体，但当前一代的艾滋病毒疫苗 在这方面并没有起到有效的作用。障碍包括我们对结构和免疫学的了解有限 HIV-1 包膜三聚体。 HIVRAD 代表了应对这些挑战的创新方法 以便从根本上提高我们用疫苗产生艾滋病毒中和抗体的能力。