TY - JOUR
T1 - Development of a live, oral, attenuated vaccine against el tor cholera
AU - Taylor, David N.
AU - Killeen, Kevin P.
AU - Hack, Dallas C.
AU - Kenner, Julie R.
AU - Coster, Trinka S.
AU - Beattie, David T.
AU - Ezzell, John
AU - Hyman, Tracy
AU - Trofa, Andrew
AU - Sjogren, Maria H.
AU - Friedlander, Arthur
AU - Mekalanos, John J.
AU - Sadoff, Jerald C.
PY - 1994/12
Y1 - 1994/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0028117638&partnerID=8YFLogxK
U2 - 10.1093/infdis/170.6.1518
DO - 10.1093/infdis/170.6.1518
M3 - Article
C2 - 7995992
AN - SCOPUS:0028117638
SN - 0022-1899
VL - 170
SP - 1518
EP - 1523
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 6
ER -