Validation and characterization of a human volunteer challenge model for cholera by using frozen bacteria of the new Vibrio cholerae epidemic serotype, O139

Until recently, all epidemic strains of Vibrio cholerae were of the O1 sero type. Current epidemics have also been caused by a new serotype, Vibrio cho lerae O139. Although the pathogenesis and clinical features of O139 cholera are similar to those of O1 cholera, immunity to serotype O1 does not confe r immunity to serotype O139, Therefore, prior to beginning vaccine efficacy studies, we sought to validate the use of a large standardized frozen inoc ulum of virulent V. cholerae O139 4260B for use in a human volunteer challe nge model. Healthy volunteers (n = 25) were recruited for an Internal Revie w Board-approved inpatient dose-escalation challenge, Our goal was to ident ify a dose at which the cholera attack rate and the geometric mean purge we re sufficient for determining vaccine efficacy against moderate and severe disease. At a dose of 10(5) CFU 8 of 10 volunteers experienced purging and had a positive stool culture far V. cholerae. However, at this dose, the ge ometric mean stool volume of 2,175 g was insufficient by study criteria, At a dose of 10(6) CFU, 14 of 15 volunteers experienced purging, with a geome tric mean stool volume of 5,621 g, Disease severity was significantly great er in volunteers with blood group O than those with non-O blood types (10,3 53 g versus 3,555 g, P < 0.001), Following challenge, all volunteers demons trated a significant rise in antitoxin antibodies but the serum vibriocidal titer nas attenuated compared to that seen after challenge dth an O1 strai n. This model provides a reproducible illness of sufficient severity for te sting the efficacies of new O139 or combined O1-O139 vaccines.