CHOLERA: PATHOGENESIS AND IMMUNOLOGY

霍乱：发病机制和免疫学

• 批准号: 3565455
• 负责人: Richard A. Finkelstein
• 金额: $ 15.68万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-04-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3565455
• 关键词: Vibrio cholerae; active immunization; antibacterial antibody; bacterial DNA; bacterial antigens; bacterial genetics; bacterial proteins; bactericidal immunity; biotechnology; cholera; cholera toxin; cholera vaccine; cow; diarrhea; enterotoxins; gastrointestinal epithelium; gel electrophoresis; gene mutation; genetic manipulation; genetic mapping; genetic strain; human tissue; immunity; laboratory mouse; laboratory rabbit; microorganism culture; microorganism hemagglutinin; microorganism immunology; monoclonal antibody; mutant; nucleic acid sequence; peptide chemical synthesis; serotyping; structural genes; surface antigens; synthetic peptide; synthetic vaccines; virulence

The goals of this research are to contribute to the complete understanding of the pathogenesis and immunology of cholera at both the organismal and the molecular levels with the expectation that this will lead to the development of rational and effective means of immunoprophylaxis. As cholera is the prototype of an expanding number of enterotoxic enteropathies, the observations are pertinent to the larger global problem of secretory diarrheal disease. It is clear that the disease, cholera, is an effective immunizing process which presents to the human host a consortium of products elaborated by the cholera vibrios growing in vivo. These include: colonization factors (as yet undefined); surface components such as the lipopolysaccharide and outer membrane proteins; the HA/protease; other enzymes; the mannose-sensitive (El Tor biotype) and other hemagglutinins; the flagellum; and the enterotoxin. This proposal specifically addresses: the identification and characterization of factor(s) participating in adherence of Vibrio cholerae to intestinal epithelium; outer membrane antigens (particularly novel iron-regulated proteins expressed in vivo); and the definition of antigens and antibodies which may be protective [including functional domains and epitopes on the immunodominant, binding, choleragenoid (B-subunit pentamer) portion of the cholera enterotoxin]. Technology includes: bacterial binding studies; protein separation and analysis with SDS-PAGE and immunoblotting; micro-antibacterial assays involving protein components of mothers' milk, polyclonal and monoclonal antibacterial antibodies; and antitoxic monoclonal antibodies and synthetic peptides of the cholera enterotoxin with the objective of developing a synthetic vaccine.

这项研究的目标是促进全面理解 霍乱的发病机制和免疫学在机体和免疫学方面的研究 分子水平，预计这将导致 开发合理有效的免疫预防手段。 作为 霍乱是越来越多的肠毒素的原型 肠病，观察结果与更大的全球问题相关 分泌性腹泻病。 显然，霍乱这种疾病是 一种有效的免疫过程，向人类宿主提供 由体内生长的霍乱弧菌精心制作的产品联盟。 其中包括： 定植因素（尚未定义）；表面成分 如脂多糖和外膜蛋白；这 透明质酸/蛋白酶；其他酶；甘露糖敏感（El Tor 生物型）和 其他血凝素；鞭毛；和肠毒素。 这个提议 具体解决：识别和表征 参与霍乱弧菌粘附肠道的因素 上皮；外膜抗原（特别是新型铁调节抗原） 体内表达的蛋白质）；以及抗原和抗体的定义 这可能是保护性的[包括功能域和表位 免疫显性、结合性、类利胆素（B 亚基五聚体）部分 霍乱肠毒素]。 技术包括：细菌结合研究； 使用 SDS-PAGE 和免疫印迹进行蛋白质分离和分析； 涉及母乳蛋白质成分的微量抗菌测定， 多克隆和单克隆抗菌抗体；和抗毒 霍乱肠毒素的单克隆抗体和合成肽 目的是开发合成疫苗。