To provide optimum protection against classical and El Tor biotypes of Vibrio cholerae O1, a single-dose, oral cholera vaccine was developed by combining two live, attenuated vaccine strains, CVD 103-HgR (classical, Inaba) and CVD 111 (El Tor, Ogawa). The vaccines were formulated in a double-chamber sachet; one chamber contained lyophilized bacteria, and the other contained buffer. In the first study, 23 U.S. adult volunteers received CV 103-HgR at 108 CFU plus CVD 111 at 108, 107, or 106 CFU, CVD 111 alone at 107 CFU, or placebo. In the second study, 275 Peruvian adults were randomized to receive CVD 103-HgR at 109 CFU plus CVD 111 at 109 or 108 CFU, CVD 111 alone at 109 CFU, CVD 103-HgR alone at 109 CFU, or placebo. Three of 15 U.S. volunteers who received CVD 111 at 107 or 108 CFU developed mild diarrhea, compared to none of 4 who received CVD 111 at 106 CFU and 1 of 4 who received placebo. Twelve (63%) of 19 vaccine recipients shed the El Tor vaccine strain. All but one volunteer developed significant Ogawa and Inaba vibriocidal antibody titers. Volunteers who received CVD 111 at 107 CFU had geometric mean Ogawa titers four to five times higher than those of volunteers who received the lower dose. In the second study, all dosage regimens were well tolerated in Peruvians. About 20% of volunteers who received CVD 111 at the high dose excreted the El Tor organism, compared to 7% in the low-dose group. CVD 111 was detected in the stools of two placebo recipients, neither of whom had symptoms or seroconverted. In all vaccine groups 69 to 76% developed fourfold rises in Inaba vibriocidal antibodies. Among those who received the bivalent vaccine, 53 to 75% also developed significant rises in Ogawa vibriocidal antibodies. We conclude that it is feasible to produce a single-dose, oral bivalent vaccine that is safe and immunogenic against both biotypes (El Tor and classical) and both serotypes (Inaba and Ogawa) of cholera for populations in both developed and developing parts of the world.
ASJC Scopus subject areas
- Infectious Diseases