Safety, immunogenicity, and efficacy of live attenuated Vibrio cholerae O139 vaccine prototype.
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.
Coster
T S
TS
Clinical Studies Branch, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.
Killeen
K P
KP
Waldor
M K
MK
Beattie
D T
DT
Spriggs
D R
DR
Kenner
J R
JR
Trofa
A
A
Sadoff
J C
JC
Mekalanos
J J
JJ
Taylor
D N
DN
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
D000907:Antibodies, Bacterial; D022121:Cholera Vaccines; D014613:Vaccines, Attenuated