Administrative Core

参见说明）： 这个HIVRAD项目建立在我们最近成功地产生稳定的，蛋白水解成熟的 gp 140三聚体（SOSIP gp 140 s）在拓扑结构和抗原性上模拟病毒体相关包膜（Env）。 这一艾滋病毒防治方案的总体目标反映在三个主要里程碑：1）确定 裂解Env三聚体在<4 A分辨率下的结构，2）证明了克服HIV-1 Env’s的方法 免疫抑制特性，和3）鉴定增强异源中和SOSIP三聚体疫苗 不同的HIV-1分离株核心A将负责艾滋病毒防治和研究中心的全面科学领导。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 Env疫苗设计，摩尔博士）和项目2（HIV-1 Env三聚体晶体学， Wilson），核心B（三聚体生产和免疫原性试验，Dr. Olson）提供技术支持。 核心项目A将提供实现艾滋病毒/艾滋病防治战略目标所需的广泛的管理支助 程序.核心A的主要功能可以根据三个具体目标进行分组：1）提供总体 科学指导和协调计划; 2）促进研究数据和资源的共享 在计划内，并与更广泛的科学界;和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完成， 在每个职能领域具有丰富行业经验的专业人士。核心活动是 这是艾滋病防治计划取得全面成功的关键。 核心A将促进项目1、项目2和项目3之间及时交换材料、数据和其他信息， 项目2和其他合作者。节目的互动性需要这些信息 在节目中产生的材料及时与参与成员交流， 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，核心A将建立并每年 召集一个外部科学咨询小组，协助决定研究方向 程序.核心A的总体作用是最佳地协调、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，为实现艾滋病毒-1 疫苗 相关性（参见说明）： 世界上有近1%的人口感染了艾滋病毒，迫切需要预防性疫苗。最 有效的疫苗可以引发抗体，可以中和病原体，但目前的艾滋病毒疫苗， 在这方面是无效的。障碍包括我们对结构和免疫学的有限理解 HIV-1包膜三聚体。这一艾滋病毒/艾滋病防治方案代表了应对这些挑战的一种创新方法 为了提供一个根本性的进步，在我们的能力，引发艾滋病毒中和抗体的疫苗。

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.