SAFETY, IMMUNOGENICITY, AND EFFICACY OF LIVE ATTENUATED VIBRIO-CHOLERAE O139 VACCINE PROTOTYPE

New vaccines are needed to prevent cholera caused by Vibrio cholerae O 139. Attenuated V cholerae O139 vaccines were made by deleting multipl e copies of the cholera-toxin genetic element from two virulent strain s of the organism, MO10 and Al4456. The deletion mutants were further modified by insertion of a construct that encoded the B subunit of cho lera toxin, thus generating strains Bengal-3 and VRI-16, A stable spon taneous nonmotile derivative of Bengal-3 was isolated end designated B engal-15; VRI-16 is naturally non-motile. Bengal-3, Bengal-15, and VRI -16 were evaluated as oral single-dose cholera vaccine candidates in 4 volunteers each, and MO10 was given to 3 volunteers, 1 of 4 volunteer s who received Bengal-3 and all 3 who received MO10 had diarrhoea, VRI -16 caused no significant symptoms but was not immunogenic. Bengal-15 produced few symptoms and was nearly as immunogenic as MO10. Subsequen tly, Bengal-15 was given to 10 volunteers at a dose of 10(6) colony-fo rming units. No volunteers had diarrhoea, and other subjective symptom s were as common in vaccinees as in 3 buffer recipients. 1 month after vaccination, 7 vaccinees, the 3 buffer recipients, and 3 unimmunised subjects were challenged with 5x10(6) colony-forming units of V choler ae O139. 5 of 6 controls had cholera-like diarrhoea, By contrast, 1 of 7 vaccinees had diarrhoea, which was mild and had a long incubation p eriod. Vaccine protective efficacy was 83%. Our results indicate the B engal-15 is a safe live attenuated vaccine candidate for cholera cause d by the O139 serogroup.