CHOLERA: PATHOGENESIS AND IMMUNOLOGY

这项研究的长期目标是为完成 对霍乱发病机制和免疫机制的认识 生物体和分子水平。预计这一理解 将导致制定合理有效的方法 免疫预防以及药物干预和 在疾病确实发生的时候进行治疗。因为霍乱是一种 肠毒性肠病的数量不断扩大，观察到的将是 与分泌性腹泻病这一更大的全球问题有关。我们的 具体的当务之急是了解(S)参与的机制 病毒攻击后产生的坚固而持久的免疫力 疾病本身，以及活着的人诱导的实质性免疫力 减毒A-B+霍乱弧菌候选疫苗株，德克萨斯州 STAR-SR(由我们之前制作)，在志愿者研究中揭示。它 我们的论点是，殖民因素(S)[粘附素(S)] 霍乱弧菌与肠毒素一样重要 霍乱的发病机制、康复和免疫学。因此，我们建议 继续研究丹参的作用性质和作用机制 血凝素/蛋白水解酶/“霍乱凝集素”，我们已经描述过了 与其他血凝素一样(定植因子？)由霍乱产生 弧菌。我们希望确定对定植的抗体 S因子在免疫中起着重要作用。我们还建议研究 霍乱病毒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 德克萨斯州Star-SR突变体TO A基因的遗传损伤性质 确定是否产生了缺失，以便突变体可能是 预计在基因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.