CHOLERA: PATHOGENESIS AND IMMUNOLOGY

霍乱：发病机制和免疫学

• 批准号: 3444527
• 负责人: Richard A. Finkelstein
• 金额: $ 12.62万
• 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 1986-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3444527
• 关键词: Vibrio cholerae; active immunization; antibacterial antibody; antibody formation; attenuated microorganism; bacterial genetics; bactericidal immunity; cholera; cholera toxin; cholera vaccine; diarrhea; enterotoxins; gastrointestinal epithelium; gene mutation; genetic strain; hemolysin; host organism interaction; immunity; microorganism culture; mutant; serotyping; virulence

The long range goals of this research are to contribute to the complete understanding of the pathogenesis and immunity of cholera at both the organismal and molecular levels. It is expected that this understanding will lead to the development of rational and effective methods of immunoprophylaxis as well as methods of pharmacologic intervention and treatment when the disease does occur. As cholera is the prototype of an expanding number of enterotoxic enteropathies, the observations will be pertinent to the larger global problem of secretory dirrheal disease. Our specific immediate concerns are to understand the mechanism(s) involved in the solid and lasting immunity which is produced following an attack of the disease itself, and the substantial immunity which is induced by the living attenuated A-B+ mutant Vibrio cholerae candidate vaccine strain, Texas Star-SR (produced by us, previously), as revealed in volunteer studies. It is our contention that the colonization factor(s) [adhesin(s)] of the cholera vibrios are equally as important as the enterotoxin in the pathogenesis, recovery from and immunology of cholera. Thus we propose to continue our studies on the nature and mechanism of action of the hemagglutinin/protease/"cholera lectin", which we have described, as well as the other hemagglutinins (colonization factors?) produced by cholera vibrios. We wish to determine whether antibody to the colonization factor(s) plays a significant role in immunity. We also propose to study the similarities and differences in structure and antigenicity of cholera vibrios grown in vitro and in vivo. And we wish to define further the nature of the genetic lesion in the A gene of the Texas Star-SR mutant to determine whether deletions were produced so that the mutant may be predicted to be genetically, as well as operationally, stable.

这项研究的长期目标是为完整的研究做出贡献 了解霍乱的发病机制和免疫 有机体和分子水平。 预计这种理解 将导致合理有效的方法的发展 免疫预防以及药物干预方法 当疾病确实发生时进行治疗。 由于霍乱是一种疾病的原型 随着肠毒性肠病的数量不断增加，观察结果将是 与更大的全球性分泌性腹泻病问题相关。 我们的 具体的直接关注点是了解涉及的机制 受到病毒攻击后产生的牢固而持久的免疫力 疾病本身，以及由活体诱导的大量免疫力 减毒 A-B+ 霍乱弧菌候选疫苗株，德克萨斯州 Star-SR（之前由我们制作），如志愿者研究所示。 它 我们的论点是定植因子[粘附素] 霍乱弧菌与肠毒素同样重要 霍乱的发病机制、恢复和免疫学。 因此我们建议 继续研究其性质和作用机制 血凝素/蛋白酶/“霍乱凝集素”，我们也已经描述过 霍乱产生的其他血凝素（定植因子？） 弧菌。 我们希望确定是否有针对定植的抗体 因子在免疫中起着重要作用。 我们也建议学习 霍乱的结构和抗原性的异同 体外和体内生长的弧菌。 我们希望进一步定义 Texas Star-SR 突变体 A 基因中遗传损伤的性质 确定是否产生缺失，以便突变体可能是 预计在遗传上和操作上都是稳定的。