Advancing a second generation C. difficile vaccine

推进第二代艰难梭菌疫苗

• 批准号: 10625172
• 负责人: Mark L Lang
• 金额: $ 131.52万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-25 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10625172
• 关键词: Advanced Development; Affect; Antibodies; Antibody Response; Area; Biometry; Cell Compartmentation; Centers of Research Excellence; Clostridium difficile; Collaborations; Communicable Diseases; Communities; Complement; Development; Disease; Engineering; Enteral; Enteric Nervous System; Equilibrium; Faculty; Failure; Funding; Generations; Goals; Human; Humoral Immunities; Immune; Immune Evasion; Immune response; Immune system; Immunity; Infection; Institution; Investigation; Joints; Knowledge; Mediating; Memory B-Lymphocyte; Nervous System; Oklahoma; Outcome; Pathogenesis; Pathogenicity; Pathology; Patients; Preclinical Testing; Program Description; Public Health; Research; Research Personnel; Research Project Grants; Resources; Signal Transduction; Testing; Toxin; United States National Institutes of Health; Vaccination; Vaccine Clinical Trial; Vaccinee; Vaccines; Work; antitoxin; arm; base; design; experimental study; innovation; insight; interest; member; microbial; pathogen; pathogenic bacteria; programs; recruit; recurrent infection; response; success; vaccination strategy; vaccine candidate; vaccine evaluation; vaccine failure; vaccine response; vaccine strategy; vaccine-induced immunity

PROJECT SUMMARY (Overall) Our goal in the Oklahoma C. difficile U19 program is to transform a strong research base on enteric bacterial pathogens into a nationally-recognized center of excellence for research on C. difficile. Our research goals, commensurate with RFA-AI-022-001 are to provide basic knowledge that explains why vaccine-induced immunity provides suboptimal protection against C. difficile, to understand the human memory B cell response to the pathogen, and to advance the development and testing of second generation vaccine candidates. To achieve these goals, three independent but complementary Research Projects have been devised which are supported by an Administrative Core that includes bio-statistics support, and a Research Core to allow for integrated and consistent C. difficile challenge experiments within and between the Research Projects. The following Specific Aims will therefore be accomplished: Specific Aim 1: Establish a center of excellence for research on C. difficile. Specific Aim 2: Test a second-generation vaccine candidate that shifts the balance between the pathogen and host resulting in a more efficacious vaccine response and determine how C. difficile toxin B subverts those responses (Project 1). Specific Aim 3: Determine the functional diversity of human TcdB- specific memory B cell-derived antibody (Project 2). Specific Aim 4: Determine the impact of TcdA and TcdB on the enteric nervous system-coordinated humoral response to vaccination and infection (Project 3). These efforts will also be supported by NIH-funded programs at OUHSC that provide vital additional resources. By the end of the first five year funding period we will advance the goal of understanding why vaccine responses to C. difficile are sub-optimal, advance a second generation vaccine, and establish the means for a sustained research program on C. difficile.

项目摘要（总体） 我们在俄克拉荷马州艰难梭菌U19计划中的目标是改变肠细菌的强大研究基础 病原体成为艰难梭菌研究的全国认可的卓越中心。我们的研究目标， 与RFA-AI-022-001相称 免疫力为艰难梭菌提供了次优的保护，以了解人类记忆B细胞反应 到病原体，并推进第二代疫苗的开发和测试。到 实现这些目标，已经设计了三个独立但互补的研究项目 由包括生物统计数据支持的行政核心支持，以及允许的研究核心 研究项目内和之间的综合艰难梭菌挑战实验。这 因此，将实现以下具体目标：具体目标1：建立一个卓越中心 艰难梭菌的研究。特定目标2：测试转移余额的第二代疫苗候选者 在病原体和宿主之间产生更有效的疫苗反应，并确定艰难梭菌如何 毒素B颠覆了这些反应（项目1）。特定目的3：确定人类TCDB-的功能多样性 特定的内存B细胞衍生抗体（项目2）。特定目标4：确定TCDA和TCDB对 对疫苗接种和感染的肠神经系统协调的体液反应（项目3）。这些努力 NIH资助的计划也将支持OUHSC提供重要的额外资源。到结束 在第一个五年的资金期间，我们将促进了解为什么疫苗对艰难梭菌的反应 是最佳的，推进第二代疫苗，并为持续研究建立手段 艰难梭菌的计划。