title: 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 three months after vaccination.
abstract: CVD 103-HgR is a live oral cholera vaccine strain constructed by deleting 94% of the gene for the enzymatically active A subunit of cholera toxin from classical Inaba Vibrio cholerae O1 569B; the strain also contains a mercury 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 randomized, double-blind, placebo-controlled, multicenter study of vaccine efficacy was designed to test longer-term protection of CVD 103-HgR against moderate and severe El Tor cholera in U.S. volunteers. A total of 85 volunteers (50 at the University of Maryland and 35 at Children's Hospital Medical Center/University of Cincinnati) were recruited for vaccination and challenge with wild-type V. cholerae El Tor Inaba. Volunteers were randomized in a double-blind manner to receive, with buffer, a single oral dose of either CVD 103-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, prepared from a standardized frozen inoculum. Ninety-one percent of the vaccinees had a >/=4-fold rise in serum vibriocidal antibodies after vaccination. After challenge, 9 (39%) of the 23 placebo recipients and 1 (4%) of the 28 vaccinees had moderate or severe diarrhea (>/=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. cholerae excretion among placebo recipients was 1.1 x 10(7) CFU/g and among vaccinees 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.
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. ctacket@medicine.umaryland.edu
authors.forename: C O
authors.initials: CO
authors.lastname: Tacket
authors.forename: M B
authors.initials: MB
authors.lastname: Cohen
authors.forename: S S
authors.initials: SS
authors.lastname: Wasserman
authors.forename: G
authors.initials: G
authors.lastname: Losonsky
authors.forename: S
authors.initials: S
authors.lastname: Livio
authors.forename: K
authors.initials: K
authors.lastname: Kotloff
authors.forename: R
authors.initials: R
authors.lastname: Edelman
authors.forename: J B
authors.initials: JB
authors.lastname: Kaper
authors.forename: S J
authors.initials: SJ
authors.lastname: Cryz
authors.forename: R A
authors.initials: RA
authors.lastname: Giannella
authors.forename: G
authors.initials: G
authors.lastname: Schiff
authors.forename: M M
authors.initials: MM
authors.lastname: Levine
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D002771:Cholera / Q000517:prevention & control*; D022121:Cholera Vaccines / Q000008:administration & dosage / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D014611:Vaccination; D014734:Vibrio cholerae / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D000907:Antibodies, Bacterial; D022121:Cholera Vaccines