Development of a live, oral, attenuated vaccine against el tor cholera

David N. Taylor, Kevin P. Killeen, Dallas C. Hack, Julie R. Kenner, Trinka S. Coster, David T. Beattie, John Ezzell, Tracy Hyman, Andrew Trofa, Maria H. Sjogren, Arthur Friedlander, John J. Mekalanos, Jerald C. Sadoff

Research output: Contribution to journalArticle

Abstract

Vibrio cholerae EI Tor strains from Peru, Bangladesh, and Bahrain were attenuated by deletion of a genetic element that encodes virulence factors and RSI. The B subunit of ctx (ctxB) was reintroduced into the recA gene of the deletion mutants, rendering them unable to recombine with exogenous genetic elements and generating Peru-3, Bang-3, and Bah-3. Fifteen volunteers received one dose of various vaccine strains at 4 × 106 to 1 × 108 cfu. All strains colonized the gut. A ≥ 4-fold rise in vibriocidal titer was observed in 14 volunteers, with titers of ≥ 1600 in 13. Peru-3 was the least reactogenic, but 2 of 6 volunteers had loose stools. Peru-14, a filamentous motility-deficient mutant of Peru-J, was well tolerated and colonized 18 of 21 volunteers at doses of 2 × 106 to 1 × 109 cfu. Also, when 8 Peru-3 or Peru-S vaccinees, 5 Peru-14 vaccinees, and 8 controls were challenged with 2 × 106 cfu V. cholerae EI Tor Inaba (NI6961), 11 vaccinees were protected compared with no controls. Peru-14 shows promise as a safe, effective, single-dose oral vaccine against EI Tor cholera.

Original languageEnglish (US)
Pages (from-to)1518-1523
Number of pages6
JournalJournal of Infectious Diseases
Volume170
Issue number6
DOIs
StatePublished - Dec 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Taylor, D. N., Killeen, K. P., Hack, D. C., Kenner, J. R., Coster, T. S., Beattie, D. T., Ezzell, J., Hyman, T., Trofa, A., Sjogren, M. H., Friedlander, A., Mekalanos, J. J., & Sadoff, J. C. (1994). Development of a live, oral, attenuated vaccine against el tor cholera. Journal of Infectious Diseases, 170(6), 1518-1523. https://doi.org/10.1093/infdis/170.6.1518