Neisserial OMV Vaccines

奈瑟氏菌 OMV 疫苗

• 批准号: 10588243
• 负责人: Ann E. Jerse
• 金额: $ 20.19万
• 依托单位: HENRY M. JACKSON FDN FOR THE ADV MIL/MED
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-26 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10588243
• 关键词: Acceleration; Adjuvant; Antibiotic Resistance; Antigens; Biological Assay; Chlamydia; Clinical Trials; Data; Data Protection; Databases; Dose; Drug Metabolic Detoxication; Effectiveness; Epidemiology; Epitopes; Genetic; Goals; Gonorrhea; Health; Human; Immune Sera; Immune response; Immunization; Immunize; Immunosuppression; Individual; Infection; Inflammation; Ion Channel; Iron; Laboratories; Licensing; Lipid A; Measures; Membrane; Membrane Proteins; Methods; Modeling; Mucous Membrane; Mus; Neisseria gonorrhoeae; Neisseria meningitidis; Pathogenesis; Pharmaceutical Preparations; Preclinical Testing; Proteins; Public Health; Publishing; Qualifying; Quality Control; Recombinants; Regimen; Reproductive Tract Infections; Research; Research Personnel; Risk; Risk Reduction; Route; Safe Sex; Safety; Serogroup B Neisseria meningitidis; Sex Counseling; Standardization; Surface; Testing; Universities; Vaccination; Vaccine Adjuvant; Vaccines; Vesicle; Virus-like particle; Work; burden of illness; co-infection; design; efflux pump; epidemiologic data; gonorrhea vaccine; in vivo; manufacturability; mouse model; nanodisk; next generation; novel; overexpression; pre-clinical assessment; reproductive tract; resistant strain; tool; vaccine candidate; vaccine development; vaccine efficacy; vaccine evaluation; vaccine platform; vaccine-induced immunity

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.

抽象的 项目2的目标：淋病“奈瑟菌外膜囊泡疫苗” 疫苗合作研究中心（GV CRC）将开发候选淋病奈瑟菌 (Ng) 和脑膜炎奈瑟菌 (Nm) OMV 疫苗可预防淋病。前提 该应用的重点是可以使用奈瑟氏菌 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。这个前提得到了令人兴奋的支持 新的流行病学证据表明 B 群 Nm OMV 可以降低淋病风险 我们实验室的初步数据显示两种不同的基于 Nm OMV 的疫苗 加速 Ng 从实验感染小鼠中的清除。具体目标 申请的目的是： 1) 进一步开发一种新型 Nm OMV 疫苗，该疫苗具有体内功效 针对 Ng，2) 开发 Ng OMV 疫苗，增加有希望的疫苗靶标的表达， 3) 开发下一代 Ng 和/或 Nm OMV 疫苗，由 OMV 与 纳米盘展示蛋白疫苗或 Ng 表位靶向病毒样颗粒疫苗 由其他 GV CRC 研究人员开发。 OMV 将接受标准化质量控制 结构完整性和成分以及使用最先进技术进行严格的临床前评估 用于测量 Ng 降低小鼠模型的宿主免疫反应和体内功效的测定法 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反应并保护的能力 对抗小鼠生殖道感染，将被选择进行进一步的临床前研究 测试和临床试验。我们还将测试许可佐剂对缓解 Ng- 的效果。 Ng OMV 疫苗功效诱导免疫抑制并利用免疫数据库 从所有候选疫苗获得的反应和体内保护数据来定义机制 疫苗诱导的免疫。