Neisserial OMV Vaccines

奈瑟氏菌 OMV 疫苗

• 批准号: 10362595
• 负责人: Ann E. Jerse
• 金额: $ 21.75万
• 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 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10362595
• 关键词: Adjuvant; Antibiotic Resistance; Antigens; Biological Assay; Chlamydia; Clinical Trials; Conflict (Psychology); Data; Data Protection; Databases; Dose; Effectiveness; Epidemiology; Epitopes; Goals; Gonorrhea; Health; Human; Immune Sera; Immune response; Immunization; Immunize; Immunosuppression; Individual; Infection; Inflammation; Ion Channel; Iron; Laboratories; Lipid A; Measures; Membrane; Membrane Proteins; Methods; Modeling; Mucous Membrane; Mus; Neisseria gonorrhoeae; Neisseria meningitidis; Pathogenesis; Pharmaceutical Preparations; Preclinical Testing; Proteins; Public Health; Publishing; Quality Control; Recombinants; Regimen; Research; Research Personnel; Risk; Route; Safe Sex; Safety; Serogroup B Neisseria meningitidis; Sex Counseling; Standardization; Surface; Testing; Universities; Vaccination; Vaccine Adjuvant; Vaccines; Vesicle; Virus-like particle; Work; base; burden of illness; co-infection; design; efflux pump; epidemiologic data; genetic vaccine; 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.

摘要 项目2的目标：淋病内的“NeisSeries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)和奈瑟氏菌脑膜炎(Nm)OMV疫苗，防止淋病。前提是 这一应用的关键是可以利用新的系列OMV开发出有效的淋病疫苗 含有明确的表面暴露的保护性抗原。这一前提是由激动人心的 新的流行病学证据表明，B组Nm OMV可以降低淋病和 来自我们实验室的初步数据显示，两种不同的Nm OMV疫苗 加速从实验感染的小鼠中清除Ng。《公约》的具体目标 应用是：1)进一步开发一种新的具有体内效力的Nm OMV疫苗 针对Ng，2)开发增加有希望的疫苗靶点表达的Ng OMV疫苗， 3)开发下一代OMV和/或Nm OMV疫苗 纳米盘展示的蛋白质疫苗或靶向Ng表位的病毒样颗粒疫苗 由其他GV CRC调查人员开发。OMVS将接受标准化的质量控制 结构的完整性和组成以及使用最先进的技术进行严格的临床前评估 检测Ng low小鼠模型宿主免疫反应和体内疗效的方法 上生殖道(LRT、URT)感染。最有希望的疫苗，由 诱导全身和粘膜体液和细胞免疫反应和保护的能力 抗小鼠生殖道感染，将被选为进一步的临床前研究 测试和临床试验。我们亦会测试领有牌照的佐剂对纾缓非典型肺炎的效果。 Ng OMV疫苗的诱导免疫抑制效果及免疫数据库的利用 从所有候选疫苗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。