Safety, Immunogenicity, and Protective Efficacy of the Whole‐Cell/Recombinant B Subunit (WC/rBS) Oral Cholera Vaccine Against Travelers' Diarrhea

Background: A prospective, randomized, double‐blind, placebo‐controlled trial of WC/rBS oral cholera vaccine was conducted in 502 U.S. college students attending summer educational programs in Mexico. Methods: Two doses of vaccine (or placebo) were administered 10 days apart immediately after arrival in Mexico. Results: The vaccine was free of significant adverse side effects. Anticholera toxin seroconversion was demonstrated in 86.7% of vaccinees compared to 8.2% of controls (p < .001). Postvaccination titers varied according to disease status (travelers' diarrhea) and enteropathogen isolated when disease developed. Protective efficacy (PE) against enterotoxigenic Escherichia coli (ETEC) diarrhea was 50% (95% Cl, 14–71 %), beginning 7 days after the second dose of WC/rBS. However, 74% of ETEC cases occurred within 7 days of the second dose, when no efficacy was demonstrated. Conclusions: Vaccines employed to prevent travelers' diarrhea will likely need to be administered before arrival in a developing country to be predictably beneficial. An unexpected finding was that infection with LT‐ETEC after primary oral cholera immunization appears to augment the antitoxin response to WC/rBS vaccine.