Immunologic response to oral cholera vaccination in a crossover study: a novel placebo effect

The authors conducted a two-period crossover study of the reactogenicity and immunogenicity of live oral cholera vaccine CVD 103-HgR among US university students. Subjects ingested 5 x 10(8) colony forming units of either killed Escherichia coli K12 placebo or vaccine, followed by the opposite treatment one week later. Surprisingly, the dynamics of the immunologic response were influenced by prior ingestion of placebo. Subjects who received placebo first showed stronger vibriocidal antibody responses 2 weeks after vaccination compared with subjects who received vaccine first; this same pattern was seen for antitoxin titers. The authors suggest that ingestion of E. coli K12 one week prior to immunization boosts the immunologic response to vaccine by an unknown mechanism. Future crossover studies that examine immunologic outcomes might be designed to explore the ubiquity of such an effect.