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.
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