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 greater than or equal to 4-fold rise in vibriocidal titer was observed in 14 volunteers, with titers of greater than or equal to 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.