Administrative Core

请参阅说明)： 这个HIVRAD计划建立在我们最近在产生稳定的、蛋白质降解成熟的 Gp140三聚体(SOSIPgp140)，在拓扑结构和抗原性上模仿病毒粒子相关的包膜(Env)。 HIVRAD计划的总体目标体现在三个主要里程碑中：1)确定 切割的环境三聚体的结构在4A分辨率，2)展示了克服HIV-1环境的方法 免疫抑制特性，以及3)鉴定引起异源中和的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……里面 此外，核心A将协调将在#年进行的高度相互依存和互动的研究 项目1(HIV-1环境疫苗设计，摩尔博士)和项目2(HIV-1环境三聚体结晶学，Dr。 由Core B(三聚体生产和免疫原性测试，Olson博士)提供技术支持。 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的主要职能可以根据三个具体目标进行归类：1)提供全面的 项目的科学指导和协调；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合作；以及3)提供统计、财务、 行政和知识产权支持。这些目标将由一个现有的团队实现 在每个职能领域都有丰富行业经验的专业人士。核心活动是 这是HIVRAD项目总体成功的核心。 核心A将促进项目1之间及时交换材料、数据和其他信息， 项目2和其他合作者。节目的互动性决定了这些信息的必要性 和在计划中产生的材料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，以便以最佳方式推进程序。此外，核心A将建立并每年 召集一个外部科学咨询小组，协助就研究方向作出决定 程序。核心A的总体作用是以最佳方式协调、指导和促进项目研究 1和项目2，以实现我们共同的目标，即从根本上推动艾滋病毒-1的传播 疫苗。 相关性(请参阅说明)： 全球近1%的人口感染了艾滋病毒，迫切需要一种预防性疫苗。多数 有效的疫苗能产生中和病原体的抗体，但当代的艾滋病毒疫苗 在这方面是无效的。障碍包括我们对结构和免疫学的有限了解 HIV-1包膜三聚体。HIVRAD代表了应对这些挑战的创新方法 为了从根本上提高我们用疫苗诱导艾滋病毒中和抗体的能力。

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.