Neisserial OMV Vaccines

摘要 项目2的目标：淋病内的“奈瑟球菌外膜囊泡疫苗” 疫苗合作研究中心（GV CRC）正在开发候选淋病奈瑟菌 (Ng)和预防淋病的脑膜炎奈瑟菌（Nm）OMV疫苗。前提 本申请的一个优点是可以使用奈瑟球菌OMV开发有效的淋病疫苗 含有确定的表面暴露的保护性抗原。这一前提得到了令人兴奋的支持 新的流行病学证据表明，血清型B Nm OMV可以降低淋病的风险， 我们实验室的初步数据显示， 加速Ng从实验感染的小鼠中的清除。的具体目标 本申请的目的是：1）进一步开发一种新的Nm OMV疫苗， 2）开发具有增加的有希望的疫苗靶标的表达的Ng OMV疫苗， 和3）开发下一代Ng和/或Nm OMV疫苗，其由OMV组合 纳米盘展示的蛋白质疫苗或Ng表位靶向的病毒样颗粒疫苗， 由其他GV CRC研究者开发。OMV将接受标准化质量控制， 结构完整性和组成，以及使用最先进技术进行严格的临床前评估 用于测量Ng降低小鼠模型中宿主免疫应答和体内功效的测定 和上生殖道（LRT，URT）感染。最有前途的疫苗，由 诱导全身和粘膜体液和细胞免疫应答并保护 针对鼠生殖道感染，将被选择用于进一步的临床前研究 测试和临床试验。我们还将测试许可的佐剂对减轻Ng- 诱导免疫抑制的Ng OMV疫苗效力和利用免疫数据库 从所有候选疫苗中获得的应答和体内保护数据，以确定机制 疫苗诱导的免疫力。

ABSTRACT The goal of Project 2: “Neisserial outer membrane vesicle vaccines” within the Gonorrhea Vaccine Cooperative Research Center (GV CRC) is to develop candidate Neisseria gonorrhoeae (Ng) and Neisseria meningitidis (Nm) OMV vaccines that protect against gonorrhea. The premise of this application is that an effective gonorrhea vaccine can be developed using neisserial OMVs containing defined surface exposed, protective antigens. This premise is supported by exciting new epidemiological evidence that serogroup B Nm OMVs can reduce the risk of gonorrhea and preliminary data from our laboratories that show two different Nm OMV-based vaccines accelerate clearance of Ng from experimentally infected mice. The Specific Aims of the application are to: 1) Further develop a novel Nm OMV vaccine that demonstrates in vivo efficacy against Ng, 2) Develop Ng OMV vaccines with increased expression of promising vaccine targets, and 3) Develop next-generation Ng and, or Nm OMV vaccines consisting of OMVs combined with nanodisc-displayed protein vaccines or Ng epitope-targeted virus-like-particle vaccines being developed by other GV CRC investigators. OMVs will undergo standardized quality control for structural integrity and composition and a rigorous pre-clinical assessment using state-of-the art assays for measuring host immune responses and in vivo efficacy in mouse models of Ng lower and upper reproductive tract (LRT, URT) infection. The most promising vaccines, defined by the capacity to induce systemic and mucosal humoral and cellular immune responses and protect against murine genital tract infection, will be selected for advancement to further pre-clinical testing and clinical trials. We will also test the effect of licensed adjuvants on alleviating Ng- induced immunosuppression of Ng OMV vaccine efficacy and utilize the database of immune responses and in vivo protection data obtained from all candidate vaccines to define mechanisms of vaccine-induced immunity.