Randomized, controlled study of the safety and immunogenicity of Peru-15, a live attenuated oral vaccine candidate for cholera, in adult volunteers in Bangladesh.
A live oral Vibrio cholerae O1 El Tor vaccine candidate, Peru-15, was studied for safety, immunogenicity, and excretion in phase 1 (inpatient) and phase 2 (outpatient) studies of Bangladeshi adults.METHODs. The study was conducted among adults, by use of a double-blind, randomized, placebo-controlled design. A single dose of Peru-15 (approximately 2 x 108 cfu) or placebo (buffer only) was given in standard bicarbonate and ascorbic acid buffer.RESULTS. Study treatment did not elicit any major adverse events in the volunteers, during either the inpatient or the outpatient phases, and there were no reports of diarrhea. V. cholerae was isolated from the stool of only 1 volunteer and was found to be genetically identical to the vaccine strain. Vibriocidal antibody responses were seen in 30 (75%) of 40 vaccine recipients and in 3 (10%) of 30 placebo recipients. Peripheral blood immunoglobulin (Ig) A and IgM antibody-secreting cell responses to lipopolysaccharide were seen in the majority of vaccine recipients (response rate, 78%--88%). Seroconversion for lipopolysaccharide-specific IgA antibodies was seen in 88% of vaccine recipients. The response in vaccine recipients was significantly higher than that in placebo recipients, in all of the immunological assays (P=.036 to <.001). A lower immunological response against cholera toxin B subunit was detected.CONCLUSIONS. The safety and immunogenicity of this Peru-15 vaccine candidate indicates the usefulness of future studies in Bangladesh, where cholera is endemic.
Qadri
Firdausi
F
International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B): Centre for Health and Population Research, Dhaka, Bangladesh. fqadri@icddrb.org
Chowdhury
Mohiul I
MI
Faruque
Shah M
SM
Salam
Mohammed A
MA
Ahmed
Tanvir
T
Begum
Yasmin A
YA
Saha
Amit
A
Alam
Mohammed S
MS
Zaman
K
K
Seidlein
Lorenz V
LV
Park
Eunsik
E
Killeen
Kevin P
KP
Mekalanos
John J
JJ
Clemens
John D
JD
Sack
David A
DA
D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D001459:Bangladesh; D022121:Cholera Vaccines / Q000009:adverse effects* / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008875:Middle Aged; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000276:immunology; D014734:Vibrio cholerae / Q000276:immunology*
D000907:Antibodies, Bacterial; D022121:Cholera Vaccines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014613:Vaccines, Attenuated