Safety, immunogenicity, and efficacy of live attenuated Vibrio cholerae 0139 vaccine prototype

K. P. Killeen, D. T. Beattie, D. R. Spriggs, M. K. Waldor, J. J. Mekalanos, T. S. Coster, J. R. Kenner, A. Trofa, J. C. Sadoff, D. N. Taylor

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)949-952
Number of pages4
JournalThe Lancet
Volume345
Issue number8955
DOIs
StatePublished - Apr 15 1995

ASJC Scopus subject areas

  • Medicine(all)

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    Killeen, K. P., Beattie, D. T., Spriggs, D. R., Waldor, M. K., Mekalanos, J. J., Coster, T. S., Kenner, J. R., Trofa, A., Sadoff, J. C., & Taylor, D. N. (1995). Safety, immunogenicity, and efficacy of live attenuated Vibrio cholerae 0139 vaccine prototype. The Lancet, 345(8955), 949-952. https://doi.org/10.1016/S0140-6736(95)90698-3