CHOLERA: PATHOGENESIS AND IMMUNOLOGY

霍乱：发病机制和免疫学

• 批准号: 3444528
• 负责人: Richard A. Finkelstein
• 金额: $ 15.38万
• 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/3444528
• 关键词: Vibrio cholerae; active immunization; antibacterial antibody; bacterial DNA; bacterial antigens; bacterial genetics; bactericidal immunity; biotechnology; cholera; cholera toxin; cholera vaccine; diarrhea; enterotoxins; gastrointestinal epithelium; gel electrophoresis; gene mutation; genetic manipulation; genetic mapping; genetic strain; human tissue; immunity; 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.

这项研究的目标是为完全理解做出贡献 霍乱的发病机理和免疫学在生物和 分子水平，期望这将导致 开发有效和有效的免疫预防手段。 作为 霍乱是扩展数量的肠毒性的原型 肠道疾病，观察结果与更大的全球问题有关 分泌性腹泻病。 显然，霍乱疾病是 一个有效的免疫过程，向人类主机呈现 由霍乱弧菌在体内生长的霍乱弧菌所阐述的产品财团。 其中包括：殖民化因素（尚未定义）；表面成分 例如脂多糖和外膜蛋白；这 ha/protease;其他酶；甘露糖敏感（El tor Biotype）和 其他血凝素蛋白；鞭毛；和肠毒素。 这个建议 专门解决：识别和表征 参与沃里奥霍乱遵循肠道的因子 上皮；外膜抗原（尤其是新型铁调节 蛋白质在体内表达）；以及抗原和抗体的定义 可能具有保护性[包括功能域和表位 免疫主导，结合，胆碱素（b-Subunit Pentamer）部分 霍乱肠毒素]。 技术包括：细菌结合研究； SDS-PAGE和免疫印迹的蛋白质分离和分析； 涉及母亲牛奶蛋白质成分的微抗细菌测定， 多克隆和单克隆抗菌抗体；和抗毒性 霍乱肠毒素的单克隆抗体和合成肽 目的是开发合成疫苗。