Development of a live, oral, attenuated vaccine against El Tor cholera.
Vibrio cholerae El Tor strains from Peru, Bangladesh, and Bahrain were attenuated by deletion of a genetic element that encodes virulence factors and RS1. 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 x 10(6) to 1 x 10(8) cfu. All strains colonized the gut. A > or = 4-fold rise in vibriocidal titer was observed in 14 volunteers, with titers of > or = 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-3, was well tolerated and colonized 18 of 21 volunteers at doses of 2 x 10(6) to 1 x 10(9) cfu. Also, when 8 Peru-3 or Peru-5 vaccinees, 5 Peru-14 vaccinees, and 8 controls were challenged with 2 x 10(6) cfu V. cholerae El Tor Inaba (N16961), 11 vaccinees were protected compared with no controls. Peru-14 shows promise as a safe, effective, single-dose oral vaccine against El Tor cholera.
Taylor
D N
DN
Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Washington, DC.
Killeen
K P
KP
Hack
D C
DC
Kenner
J R
JR
Coster
T S
TS
Beattie
D T
DT
Ezzell
J
J
Hyman
T
T
Trofa
A
A
Sjogren
M H
MH
D000293:Adolescent; D000328:Adult; D000818:Animals; D000833:Animals, Suckling; D000907:Antibodies, Bacterial / Q000097:blood; D002771:Cholera / Q000517:prevention & control*; D022121:Cholera Vaccines / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D005243:Feces / Q000382:microbiology; D005260:Female; D005798:Genes, Bacterial / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007422:Intestines / Q000382:microbiology; D008297:Male; D051379:Mice; D011995:Recombination, Genetic; D017384:Sequence Deletion; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014734:Vibrio cholerae / Q000235:genetics / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D014774:Virulence
D000907:Antibodies, Bacterial; D022121:Cholera Vaccines; D007074:Immunoglobulin G; D014613:Vaccines, Attenuated