Mechanisms of IgA - mediated immunity to Vibrio cholerae

IgA 介导的霍乱弧菌免疫机制

基本信息

批准号：
9054307
负责人：
Nicholas J. Mantis
金额：
$ 22.03万
依托单位：
WADSWORTH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-02-18 至 2018-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9054307
关键词：
Acute Affect Agglutination Anabolism Antibodies Antibody Response Appearance Bacteria Bacterial Physiology Bangladesh Binding Biological Assay Bulla Cell Membrane Permeability Cells Chloride Ion Chlorides Cholera Cholera Toxin Cholera Vaccine Communities Complex Development Diarrhea Disease Enterocytes Epidemiologic Studies Epithelial Epitopes Fab Immunoglobulins Flagella Gene Expression Genes Goals Gram-Negative Bacteria Guanosine Monophosphate Human Human Resources Immune system Immunity Immunoglobulin A Immunoglobulin G In Vitro Individual Infection Intestines Laboratories Lead Life Lipopolysaccharides Measures Mediating Membrane Membrane Potentials Microbial Biofilms Morphology Mucosal Immunity Mucous body substance Mus Neonatal Permeability Physiology Principal Investigator Production Reporting Research Research Project Grants Resistance Rural Second Messenger Systems Secretory Immunoglobulin A Series Serotyping Signal Transduction Pathway Small Intestines Staging Stress Surface Technology Testing Time Up-Regulation Vaccines Vibrio cholerae Virulence Virulence Factors Work base biological adaptation to stress cell motility enteric pathogen experience extracellular flagellum motility gene repression inhibitor/antagonist innovation intestinal epithelium mouse model oral vaccine pathogen prevent programs protective effect public health relevance response second messenger transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): The long-term goal of this research project is to develop more effective oral vaccines against Vibrio cholerae, the causative agent of cholera, a life threatening diarrheal disease that remains endemic in many parts of the developing world. While there is mounting evidence from epidemiological studies to suggest that IgA antibodies directed against bacterial lipopolysaccharide (LPS) are the primary determinants of immunity to V. cholerae, virtually nothing is known about how these antibodies affect the bacterium's capacity to colonize the intestinal epithelium. This proposal will test the hypothesis that the binding of LPS-specific IgA (and IgG) antibodies to the surface of V. cholerae has direct impact on bacterial physiology and virulence. Aim 1 will test the hypothesis that LPS-specific IgA (and IgG) antibodies induce changes in V. cholerae membrane potential, permeability and ultrastructure. Aim 2 will test the hypothesis that LPS-specific IgA (and IgG) antibodies also trigger changes in the bacterial virulence gene expression and signal transduction pathways. The principal investigator is a leading expert in the field of IgA-pathogen interactions, while key personnel have expertise in V. cholerae physiology and virulence.

描述（由申请人提供）：该研究项目的长期目标是开发针对霍乱弧菌的更有效的口服疫苗，霍乱弧菌是一种威胁生命的腹泻病，在发展中国家的许多地区仍然流行。流行病学研究中有越来越多的证据表明，针对细菌脂多糖 (LPS) 的 IgA 抗体是霍乱弧菌免疫的主要决定因素，但实际上对此一无所知关于这些抗体如何影响细菌定植肠上皮的能力，该提案将检验 LPS 特异性 IgA（和 IgG）抗体与霍乱弧菌表面的结合对细菌生理学和毒力有直接影响的假设。 1 将检验 LPS 特异性 IgA（和 IgG）抗体诱导霍乱弧菌膜电位、通透性和超微结构变化的假设目标 2 将检验该假设。 LPS 特异性 IgA（和 IgG）抗体也会引发细菌毒力基因表达和信号转导途径的变化，主要研究者是 IgA-病原体相互作用领域的领先专家，同时也是关键。工作人员拥有霍乱弧菌生理学和毒力方面的专业知识。