Novel Antigen Identification for an enterotoxigenic E coli vaccine

产肠毒素大肠杆菌疫苗的新抗原鉴定

基本信息

批准号：
10368958
负责人：
James Michael Fleckenstein
金额：
$ 62.97万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10368958
关键词：
5 year old Adjuvant Affect Antibodies Antibody Formation Antibody Response Antigenic Diversity Antigens Area B-Lymphocytes Bacteria Bacterial Adhesins Bangladesh Binding Blood specimen Cells Child Cholera Complex Cryoelectron Microscopy Data Correlations Development Diarrhea Engineering Enzymes Epitopes Escherichia coli Escherichia coli Infections Escherichia coli Vaccines Genetic Goals Growth Human Human Volunteers Immune Immune response Immunologic Memory Immunologics Immunology Impaired cognition In Vitro Individual Infection Infection prevention Intestines Lead Lectin Link Malnutrition Maps Mediating Membrane Proteins Memory Microbiology Modeling Molecular Monoclonal Antibodies Morbidity - disease rate Mucins Mucous Membrane Mus Nature Pathogenesis Patients Peptide Hydrolases Persons Plasmablast Protein Microchips Proteins Recombinants Research Personnel Resource-limited setting Resources Sampling Sanitation Small Intestines Structure Subunit Vaccines Surface Surface Antigens T memory cell Testing Thermogenesis Time Toxin Translating Vaccinated Vaccination Vaccine Antigen Vaccine Design Vaccines Water base blood group design enterotoxigenic Escherichia coli feasibility testing human monoclonal antibodies immunogenic innovation microbial mortality mouse model novel novel vaccines pan-genome pathogen polyclonal antibody protein function protein structure rational design response structural biology vaccine development vaccinology volunteer

项目摘要

Project Summary/Abstract The long-term objective of this project is to develop a safe and broadly protective vaccine for enterotoxigenic E. coli (ETEC), a common cause of diarrhea worldwide. This highly collaborative project will rely on the combined resources, and innovation of investigators with complementary expertise in molecular microbiology and microbial pathogenesis, vaccinology, immunology, and advanced state-of-the-art structural biology to investigate novel targets for ETEC vaccine development. Specifically, the project will: (1) examine whether two key surface proteins of ETEC can provoke immune recall (memory) responses that are thought to be involved in sustained protection against infection (2) develop monoclonal antibodies from circulating immune cells obtained from blood samples following natural infections (3) map where these antibodies bind on the two surface proteins that we plan to use in vaccines (4) determine the overall structure of the proteins that we plan to use in vaccines (5) test the ability of these monoclonal antibodies to neutralize protein function and the ability of the bacteria to deliver toxins (6) vaccinate mice with these proteins to test protection against infection (7) test the activity of antibodies from mice and map where antibodies from mice bind the vaccine proteins relative to the human antibodies. The project will answer fundamental questions about the nature of the two proteins that are relevant not only to ETEC but to other important pathogens that secrete similar proteins. Most importantly the project is expected to provide critical information that can be translated into efficient design of a multi-featured vaccine for ETEC that provides broad-based long-term protection.

项目概要/摘要该项目的长期目标是开发一种安全且具有广泛保护作用的产肠毒素大肠杆菌疫苗。大肠杆菌 (ETEC)，是全世界腹泻的常见原因。这个高度协作的项目将依赖于联合具有分子微生物学和互补专业知识的研究人员的资源和创新微生物发病机制、疫苗学、免疫学和先进的结构生物学研究 ETEC 疫苗开发的新目标。具体来说，该项目将： (1) 检查 ETEC 的两个关键表面蛋白是否可以激发免疫回忆（记忆）反应被认为参与持续预防感染的保护 (2) 从血液样本中获得的循环免疫细胞中开发单克隆抗体感染 (3) 绘制这些抗体与我们计划在疫苗中使用的两种表面蛋白结合的位置 (4)确定我们计划在疫苗中使用的蛋白质的整体结构 (5)测试这些单克隆抗体中和蛋白质功能的能力以及细菌的能力输送毒素 (6) 用这些蛋白质给小鼠接种疫苗以测试对感染的保护作用 (7) 测试小鼠抗体的活性并绘制小鼠抗体与疫苗蛋白结合的位置图相对于人类抗体。该项目将回答有关这两种蛋白质性质的基本问题，这些问题不仅与 ETEC 但也适用于分泌类似蛋白质的其他重要病原体。最重要的是该项目预期提供可转化为 ETEC 多功能疫苗的有效设计的关键信息提供广泛的长期保护。