CHOLERA: PATHOGENESIS AND IMMUNOLOGY

这项研究的长期目标是为完成 了解霍乱的发病机制和免疫力， 有机体和分子水平。 预计这一谅解 将导致合理和有效的方法， 免疫预防以及药物干预方法， 当疾病发生时进行治疗。 因为霍乱是一种 扩大肠中毒性肠病的数量，观察结果将是 与分泌性腹泻这一更大的全球性问题有关。 我们 具体的直接问题是了解所涉及的机制， 免疫力是一种持久的免疫力，它是在一种疾病的攻击后产生的。 疾病本身，以及由活体诱导的实质性免疫力 减毒A-B+突变霍乱弧菌候选疫苗株，德克萨斯州 Star-SR（由我们生产，以前），如志愿者研究所示。 它 我们的论点是， 霍乱弧菌与肠毒素同样重要， 霍乱的发病机制、康复和免疫学。 因此，我们建议 继续研究药物的性质和作用机制， 血凝素/蛋白酶/“霍乱凝集素”，我们已经描述过，以及 作为其他血凝素（定植因子？）由霍乱引起的 弧菌 我们希望确定是否有抗体的殖民 因子在免疫中起重要作用。 我们还建议研究 霍乱菌结构和抗原性的异同 在体外和体内生长的弧菌。 我们希望进一步定义 德克萨斯星-SR突变体A基因中遗传损伤的性质， 确定是否产生了缺失，以便突变体可以 预计在基因上和操作上都是稳定的。

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.