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Infection and Immunity, December 1999, p. 6341-6345, Vol. 67, No. 12
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

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

Carol O. Tacket,1,* Mitchell B. Cohen,2 Steven S. Wasserman,1 Genevieve Losonsky,1 Sofie Livio,1 Karen Kotloff,1 Robert Edelman,1 James B. Kaper,1 Stanley J. Cryz,3 Ralph A. Giannella,2 Gilbert Schiff,2 and Myron M. Levine1

Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland 212011; Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 452292; and Swiss Serum and Vaccine Institute, Berne, Switzerland3

Received 28 June 1999/Returned for modification 25 August 1999/Accepted 8 September 1999

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 × 108 to 8 × 108 CFU) or placebo (killed E. coli K-12). About 3 months after immunization, 51 of these volunteers were orally challenged with 105 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 × 107 CFU/g and among vaccinees was 4.9 × 102 CFU/g (P < 0.001). This vaccine could therefore be a safe and effective tool to prevent cholera in travelers.

* Corresponding author. Mailing address: Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore St., Baltimore, MD 21201. Phone: (410) 706-5328. Fax: (410) 706-4171. E-mail: ctacket{at}medicine.umaryland.edu.

Infection and Immunity, December 1999, p. 6341-6345, Vol. 67, No. 12
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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