Identification of Immunologic Mechanisms of Enhanced Ng Clearance Induced by Nm OMV-based Vaccines

Nm OMV 疫苗诱导 Ng 清除增强的免疫机制鉴定

基本信息

批准号：
10588241
负责人：
JOSEPH A DUNCAN
金额：
$ 17.35万
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 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10588241
关键词：
Acceleration Animals Antibiotic Resistance Antibodies Antibody Response Antibody titer measurement Antigen Presentation Antigen Targeting Antigens Antimicrobial Resistance B-Lymphocytes Chlamydia trachomatis Control Animal Cuba Data Development Plans Engineering FDA approved Female Genital Genitalia Gonorrhea Human Immune Immune Evasion Immune response Immunity Immunization Immunologics Infection Longitudinal, observational study Mass Vaccinations Membrane Mucous Membrane Mus Natural Immunity Neisseria Neisseria gonorrhoeae Neisseria meningitidis New Zealand Norway Outcome Play Recombinant Proteins Research Role Serogroup B Neisseria meningitidis Serum Sexual Transmission Specificity Surface Antigens T cell response T-Lymphocyte Testing Time Upper respiratory tract Vaccinated Vaccination Vaccines Vesicle bactericide clinical development cross immunity epidemiology study gonorrhea vaccine major outer membrane protein mouse model pathogen pathogenic bacteria preclinical development prevent reproductive tract research clinical testing response stem vaccine development vaccine-induced immunity

项目摘要

Abstract Neisseria gonorrhoeae (Ng) is the most prevalent sexually transmitted bacterial pathogen globally, and gonococcal antibiotic resistance continues to rise. Potentially untreatable gonorrhea is recognized as an urgent threat by WHO and the US CDC. Gonococcal vaccine development is critical to help stem the spread of antimicrobial resistant Ng. Because naturally-acquired infection does not result in immunity from subsequent infection, immune responses required for protection from infection have never been definitively established for N. gonorrhoeae. Recently, a vaccine has been developed for N. meningitidis (Nm) serogroup B, and mass vaccination campaigns with this outer membrane vesicle (OMV)-containing vaccine have demonstrated collateral reduction in gonorrhea rates. Nm-OMV vaccines also show protection in a mouse model of genital Ng infection. For the first time,we have the opportunity to study both human and murine immune responses to effective vaccines, and identify likely correlates of protection. Project 1 in the Gonorrhea Vaccine Cooperative Research Center (GV CRC) will (1) determine whether murine humoral immune responses to Nm-OMV- containing vaccines are important in protection from Ng infection; (2) identify murine cellular immune mechanisms induced by Nm-OMV-containing vaccines that contribute to protection from Ng infection; and (3) determine humoral and cellular immune responses to Ng antigens induced by Nm-OMV-containing vaccine in humans. Defining immunologic mechanisms that provide protection from Ng infection is critical to advancing Ng vaccine development.!We will engage with all 4 scientific cores of the GV CRC. Our studies will set the stage for clinical evaluation of Nm-OMV vaccines for protection from Ng and will inform vaccine development plans in other GV CRC projects.

抽象的 Neiserseria Gonorrhoeae（NG）是全球性最普遍的性传播细菌病原体，并且淋球菌抗生素耐药性继续升高。潜在的不可治疗的淋病被认为是紧急的谁和美国疾病预防控制中心的威胁。淋球菌疫苗的开发对于帮助阻止的传播至关重要抗菌素耐药Ng。因为自然获得的感染不会导致随后的免疫力从未确定感染，保护感染所需的免疫反应 N. Gonorrhoeae。最近，已经开发了一种针对脑膜炎（NM）血清群和质量的疫苗该外膜囊泡（OMV）的疫苗接种运动已证明淋病率降低。 NM-AMV疫苗还显示在生殖器的小鼠模型中 NG感染。我们第一次有机会研究人类和鼠免疫反应有效的疫苗，并确定可能的保护。淋病疫苗合作的项目1 研究中心（GV CRC）将（1）确定是否对NM-omv-- 含有疫苗对于防止NG感染很重要。（2）鉴定鼠类细胞免疫含有NM-OMV的疫苗引起的机制，有助于保护NG感染；（3）确定由NM-OMV疫苗诱导的对NG抗原的体液和细胞免疫反应人类。定义提供免受NG感染保护的免疫机制对于前进至关重要 NG疫苗开发。我们将与GV CRC的所有4个科学核心进行互动。我们的研究将确定 NM-AMV疫苗的临床评估阶段，以保护NG，并将为疫苗开发提供信息其他GV CRC项目中的计划。