Observations on the Texas Star-SR avirulent A-B+ mutant candidate cholera vaccine

Comprehensive controlled vaccine trials have revealed that neither conventional cholera vaccines nor cholera toxoid administered parenterally are effective in inducing durable immunity against cholera. The only truly effective means of immunization against cholera as yet demonstrated conclusively only in volunteers, are (a) recovery from the disease itself and (b) that observed following oral administration of living attenuated mutants. In both instances, the host is presented with a consortium of vibrio products at the important local level. Studies in our laboratory have resulted in the isolation from cholera vibrios of a soluble haemagglutinin (HA), which has inherent protease activity, and which appears to participate in adherence of the vibrios to the intestinal epithelium. Current observations indicate that this HA/lectin/protease (a) is produced in both a cell-associated and a soluble form in vivo and (b) that it hydrolyzes fibronectin, secretory immunoglobulin A (sIgA), and mucin, three host proteins which may be significant in specific and non-specific resistance. The Texas Star-SR mutant has been shown to have a mild side effect in volunteers in that, independent of the dose administered about 20% of the recipients manifest one or a few non-inconveniencing loose movements. It is possible that the mere act of intestinal colonization may alter fluid transport in the gut and that this could be a model for other diarrheal disease.