The Gonorrhea Vaccine Cooperative Research Center

摘要 淋病疫苗合作研究中心（GV CRC）的总体目标是推进有希望的 候选疫苗进一步临床前开发和临床试验。拟议的 GV CRC 是 围绕四个研究项目组织，这些项目共同将解决以下方面的巨大研究空白 使用来自个体和小鼠的人类样本研究疫苗诱导的淋病免疫力的相关性 接种了 4CMenB 疫苗，有证据表明可以预防淋病（项目 1）并且 使用疫苗平台开发针对有前景的 Ng 表面分子的候选淋病疫苗 经验证的安全性和可制造性，特别是 OMV 疫苗（项目 2）、纳米圆盘展示的蛋白质亚基 疫苗（项目 3）和表位标记的病毒样颗粒疫苗（项目 4）。疫苗靶点的选择是 基于序列保守性、诱导杀菌抗体 (Abs) 的能力、小鼠体内功效 模型，和/或被 4CMenB 免疫小鼠的 Abs 识别，这加速了 Ng 的清除 雌性小鼠下生殖道感染模型。疫苗免疫原将由集中核心制备 （核心 B）确保一致和受控的准备工作，所有候选疫苗都将接受 使用最先进的免疫学测定的系统且严格的评估过程（核心 C 和 D） 和动物感染模型（核心 E），通过四个集中科学核心的参与。安 管理核心（核心 A）将提供促进各部门之间通信所需的基础设施 中心内的不同机构以及 NIH/NIAID 项目工作人员，并协调电话会议和 项目和核心领导者之间举行会议，以促进数据交换、内部同行评审和协作。 一个常设的外部科学顾问委员会将审查第二年和第四年的科学进展，并确定哪些 疫苗将进一步进行临床前开发。

ABSTRACT The overall goal of the Gonorrhea Vaccine Cooperative Research Center (GV CRC) is to advance promising vaccine candidates towards further preclinical development and clinical trials. The proposed GV CRC is organized around four Research Projects, which collectively will address the large research gap regarding correlates of vaccine-induced immunity against gonorrhea using human samples from individuals and mice vaccinated with the 4CMenB vaccine for which there is evidence of protection against gonorrhea (Project 1) and develop candidate gonorrhea vaccines against promising Ng surface molecules using vaccine platforms with proven safety and manufacturability, specifically OMV vaccines (Project 2), nanodisc-displayed protein subunit vaccines (Project 3) and epitope-tagged virus-like particle vaccines (Project 4). The choice of vaccine targets is based on sequence conservation, capacity to induce bactericidal antibodies (Abs), in vivo efficacy in the mouse model, and, or recognition by Abs from mice immunized with 4CMenB, which accelerates Ng clearance in the female mouse model of lower genital tract infection. Vaccine immunogens will be prepared by a centralized core (Core B) to ensure consistent and controlled preparations, and all vaccine candidates will be subjected to a systematic and rigorous evaluation process that uses state-of-the-art immunological assays (Cores C and D) and animal infection models (Core E) through the participation of four centralized Scientific Cores. An Administrative Core (Core A) will provide the infrastructure needed to facilitate communications between the different institutions within the center and with NIH/NIAID program staff, and coordinate teleconferences and meetings among the Project and Core leaders to foster data exchange, internal peer review and collaboration. A standing outside Scientific Advisory Board will review scientific progress in years 2 and 4, and determine which vaccines will be advanced for further pre-clinical development.