EVALUATION OF A BIVALENT (CVD-103-HGR CVD-111) LIVE ORAL CHOLERA VACCINE IN ADULT VOLUNTEERS FROM THE UNITED-STATES AND PERU

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 (class ical, Inaba) and CVD 111 (El Tor, Ogawa), The vaccines were formulated in a double-chamber sachet; one chamber contained lyophilized bacteri a, and the other contained buffer, In the first study, 23 U.S. adult v olunteers received CVD 103-HgR at 10(8) CFU plus CVD 111 at 10(8), 10( 7), or 10(6) CFU, CVD 111 alone at 10(7) CFU, or placebo, In the secon d study, 275 Peruvian adults were randomized to receive CVD 103-HgR at 10(9) CFU plus CVD 111 at 10(9) or 10(8) CFU, CVD 111 alone at 10(9) CFU, CVD 103-HgR alone at 10(9) CFU, or placebo, Three of 15 U.S. volu nteers who received CVD 111 at 10(7) or 10(8) CFU developed mild diarr hea, compared to none of 4 who received CVD 111 at 10(6) 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 Og awa and Inaba vibriocidal antibody titers, Volunteers who received CVD 111 at 10(7) CFU had geometric mean Ogawa titers four to five times h igher than those of volunteers who received the lower dose, In the sec ond 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 det ected in the stools of two placebo recipients, neither of whom had sym ptoms or seroconverted. In all vaccine groups, 69 to 76% developed fou rfold rises in Inaba vibriocidal antibodies, Among those who received the bivalent vaccine, 53 to 75% also developed significant rises in Og awa vibriocidal antibodies, We conclude that it is feasible to produce a single dose, oral bivalent vaccine that is safe and immunogenic aga inst both biotypes (El Tor and classical) and both serotypes (Inaba an d Ogawa) of cholera for populations in both developed and developing D arts of the world.