Randomized, double-blind, placebo-controlled, multicentered trial of the efficacy of a single dose of live oral cholera vaccine CVD 103-HgR in preventing cholera following challenge with Vibrio cholerae O1 El Tor Inaba threemonths after vaccination

CVD 103-HgR is a Live oral cholera vaccine strain constructed by deleting 9 4% of the gene for the enzymatically active A subunit of cholera toxin from classical Inaba Vibrio cholerae O1 569B; the strain also contains a mercur y resistance gene as an identifying marker. This vaccine was well tolerated and immunogenic in double-blind, controlled studies and was protective in open-label studies of volunteers challenged with V. cholerae O1. A randomiz ed, double-blind, placebo-controlled, multicenter study of vaccine efficacy was designed to test longer-term protection of CVD 103-HgR against moderat e and severe El Tor cholera in U.S. volunteers. A total of 85 volunteers (5 0 at the University of Maryland and 35 at Children's Hospital Medical Cente r/University of Cincinnati) were recruited for vaccination and challenge wi th wild-type V: cholerae El Tor Inaba. Volunteers were randomized in a doub le-blind manner to receive, with buffer, a single oral dose of either CVD 1 03-HgR (2 x 10(8) to 8 x 10(8) CFU) or placebo (killed E. coli K-12). About 3 months after immunization, 51 of these volunteers,were orally challenged with 10(5) CFU of virulent V. cholerae O1 El Tor Inaba strain N16961, prep ared from a standardized frozen inoculum. Ninety-one percent of the vaccine es had a greater than or equal to 4-fold rise in serum vibriocidal antibodi es after vaccination. After challenge, 9 (39%) of the 23 placebo recipients and 1 (4%) of the 28 vaccinees had moderate or severe diarrhea (greater th an or equal to 3-liter diarrheal stool) (P < 0.01; protective efficacy, 91% ). A total of 21 (91%) of 23 placebo recipients and 5 (18%) of 28 vaccinees had any diarrhea (P < 0.001; protective efficacy, 80%). Peak stool V chole rae excretion among placebo recipients was 1.1 x 10(7) CFU/g and among vacc inees was 4.9 x 10(2) CFU/g (P < 0.001). This vaccine could therefore be a safe and effective tool to prevent cholera in travelers.