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：
9438996
负责人：
Nicholas J. Mantis
金额：
$ 4.68万
依托单位：
WADSWORTH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-20 至 2019-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9438996
关键词：
Acute Affect Agglutination Anabolism Antibodies Antibody Response Appearance Bacteria Bacterial Physiology Bangladesh Binding Biological Assay Bulla Cell Membrane Permeability Cells Chlorides Cholera Cholera Toxin Cholera Vaccine Communities Complex Development Diarrhea Dimerization Disease Enterocytes Epithelial Epitopes Fab Immunoglobulins Flagella Gene Expression Gene Expression Regulation Genetic Transcription 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 Periodicity 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 Stress Surface Technology Testing Time Up-Regulation Vaccines Vibrio cholerae Virulence Virulence Factors Work base biological adaptation to stress cell motility dimer enteric pathogen epidemiology study experience extracellular gene repression inhibitor/antagonist innovation intestinal epithelium mouse model oral vaccine pathogen prevent programs protective effect public health relevance response transcriptome sequencing virtual

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更有效的口服霍乱病原体，这是一种威胁性腹泻疾病，在发展中国家的许多地方仍然是典型的。针对针对双脂肪糖（LPS）的IgA抗体的流行病学研究，对霍乱弧菌的免疫力的可能性决定因素，关于三只疗法的虚拟离开会影响细菌的能力。 - 特异性IgA（和IgG）直接在细菌和病毒性上直接在细菌上。 ES还触发细菌毒力基因表达和信号转导途径的变化。人员在霍乱生理学和毒力方面具有专业知识。