Neisserial OMV Vaccines

奈瑟氏菌 OMV 疫苗

基本信息

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
项目类别：
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

项目摘要

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：“淋病中的奈瑟氏外膜囊泡疫苗” 疫苗合作研究中心（GV CRC）是要开发候选淋病卫星淋病（NG）和奈瑟氏菌脑膜炎（NM）OMV疫苗可预防淋病。前提此应用的是，可以使用邻居OMV开发有效的淋病疫苗包含定义的表面暴露，受保护的抗原。这个前提是令人兴奋的支持新的流行病学证据表明，血清群B NM OMV可以降低淋病和我们实验室的初步数据显示了两种不同的基于NM OMV的疫苗从实验感染的小鼠中加速NG的清除率。特定目标应用是：1）进一步开发一种新型的NM OMV疫苗，该疫苗证明了体内效率反对NG，2）开发NG OMV疫苗，并增加了承诺疫苗靶标的表达， 3）开发下一代NG和或NM OMV疫苗，由OMV组成纳米散发蛋白疫苗或NG表位靶向病毒样粒子疫苗的疫苗为由其他GV CRC调查人员开发。 OMV将接受标准化的质量控制结构完整性和组成以及使用最先进的严格的临床前评估在NG较低的小鼠模型中测量宿主免疫调查和体内效率的测定和上部生殖道（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并保护的能力针对鼠生殖道感染，将选择进步以进一步临床前测试和临床试验。我们还将测试许可调节器对减轻NG-的影响诱导NG OMV疫苗效率的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以定义机制疫苗诱导的免疫力。