Author/Authors :
K. P. Killeen، نويسنده , , D. T. Beattie، نويسنده , , D. R. Spriggs، نويسنده , , M. K. Waldor، نويسنده , , J. J. Mekalanos، نويسنده , , T. S. Coster، نويسنده , , J. R. Kenner، نويسنده , , A. Trofa، نويسنده , , J. C. Sadoff، نويسنده , , D. N. Taylor، نويسنده ,
Abstract :
New vaccines are needed to prevent cholera caused by Vibrio cholerae 0139. Attenuated V cholerae 0139 vaccines were made by deleting multiple copies of the cholera-toxin genetic element from two virulent strains of the organism, M010 and A14456. The deletion mutants were further modified by insertion of a construct that encoded the B subunit of cholera toxin, thus generating strains Bengal-3 and VRI-16. A stable spontaneous non-motile derivative of Bengal-3 was isolated and designated Bengal-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 M010 was given to 3 volunteers. 1 of 4 volunteers who received Bengal-3 and all 3 who received M010 had diarrhoea. VRI-16 caused no significant symptoms but was not immunogenic. Bengal-15 produced few symptoms and was nearly as immunogenic as M010. Subsequently, Bengal-15 was given to 10 volunteers at a dose of 108 colony-forming units. No volunteers had diarrhoea, and other subjective symptoms 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 5×106 colony-forming units of V cholerae 0139. 5 of 6 controls had cholera-like diarrhoea. By contrast, 1 of 7 vaccinees had diarrhoea, which was mild and had a long incubation period. Vaccine protective efficacy was 83%. Our results indicate the Bengal-15 is a safe live attenuated vaccine candidate for cholera caused by the 0139 serogroup.
