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 进一步的临床前开发和临床试验的候选疫苗。建议的GV CRC是 围绕四个研究项目组织，这些项目将共同解决以下方面的巨大研究差距 用人和小鼠样本研究疫苗诱导淋病免疫的相关性 接种有证据表明对淋病有保护作用的4CMenB疫苗(项目1)和 利用疫苗平台开发针对有希望的Ng表面分子的淋病候选疫苗 已证实的安全性和可制造性，特别是OMV疫苗(项目2)，纳米盘展示的蛋白质亚单位 疫苗(项目3)和表位标记的类病毒颗粒疫苗(项目4)。疫苗目标的选择是 基于序列保守性、诱导杀菌抗体(Abs)的能力、在小鼠体内的疗效 模型和/或由4CMenB免疫的小鼠的抗体识别，加速了Ng在小鼠体内的清除 雌性小鼠下生殖道感染模型。疫苗免疫原将由一个集中的核心制备 (核心B)确保一致和受控的准备，所有候选疫苗都将接受 使用最先进的免疫学分析(核心C和D)的系统和严格的评估过程 和动物感染模型(核心E)，通过四个集中的科学核心的参与。一个 管理核心(核心A)将提供所需的基础设施，以促进 中心内的不同机构和NIH/NIAID项目工作人员，并协调电话会议和 项目和核心领导之间的会议，以促进数据交换、内部同行审查和合作。 一个常设的科学咨询委员会将在第二年和第四年审查科学进展，并确定 疫苗将为进一步的临床前开发而先进。

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.