title: Safety, immunogenicity, and efficacy of live attenuated Vibrio cholerae O139 vaccine prototype.
abstract: New vaccines are needed to prevent cholera caused by Vibrio cholerae O139. Attenuated V cholerae O139 vaccines were made by deleting multiple copies of the cholera-toxin genetic element from two virulent strains of the organism, MO10 and AI4456. 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 MO10 was given to 3 volunteers. 1 of 4 volunteers 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. Subsequently, Bengal-15 was given to 10 volunteers at a dose of 10(8) 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 x 10(6) colony-forming units of V cholerae 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 period. Vaccine protective efficacy was 83%. Our results indicate the Bengal-15 is a safe live attenuated vaccine candidate for cholera caused by the O139 serogroup.
authors.affiliation: Clinical Studies Branch, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.
authors.forename: T S
authors.initials: TS
authors.lastname: Coster
authors.forename: K P
authors.initials: KP
authors.lastname: Killeen
authors.forename: M K
authors.initials: MK
authors.lastname: Waldor
authors.forename: D T
authors.initials: DT
authors.lastname: Beattie
authors.forename: D R
authors.initials: DR
authors.lastname: Spriggs
authors.forename: J R
authors.initials: JR
authors.lastname: Kenner
authors.forename: A
authors.initials: A
authors.lastname: Trofa
authors.forename: J C
authors.initials: JC
authors.lastname: Sadoff
authors.forename: J J
authors.initials: JJ
authors.lastname: Mekalanos
authors.forename: D N
authors.initials: DN
authors.lastname: Taylor
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D002771:Cholera / Q000517:prevention & control; D022121:Cholera Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D004311:Double-Blind Method; D006801:Humans; D014613:Vaccines, Attenuated; D014734:Vibrio cholerae / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D022121:Cholera Vaccines; D014613:Vaccines, Attenuated