Safety and immunogenicity of a single oral dose of recombinant double mutant heat-labile toxin derived from enterotoxigenic Escherichia coli.
Enterotoxigenic Escherichia coli (ETEC) is a primary cause of traveler's diarrhea for which there is no licensed vaccine. This phase 1 trial determined the safety and immunogenicity of a recombinantly produced double mutant heat-labile enterotoxin (dmLT) of ETEC. It was administered as a single oral dose of dmLT in escalating doses of 5 μg, 25 μg, 50 μg, and 100 μg, followed by a 72-h inpatient observation, outpatient visits at 8, 14, and 28 days, and telephone calls at 2 and 6 months postvaccination. Safety was assessed by frequency of adverse events, and immune responses determined after immunization included dmLT-specific serum IgA and IgG, fecal IgA, antibody-secreting cells (ASC), and antibodies in lymphocyte supernatant (ALS) responses. All doses were well tolerated by the 36 healthy adults enrolled. Immune responses were limited in the 5- and 25-μg dose recipients. The 50-μg dose recipients trended toward stronger responses than the 100-μg dose recipients by serum IgA (67% versus 33%, P = 0.22), serum IgG (58% versus 33%, P = 0.41), and fecal IgA (58% versus 33%, P = 0.41). By day 14 postvaccination, there were significantly more positive responders (≥4-fold increase from baseline) among the 50- versus 100-μg dose recipients for serum IgA (P = 0.036) but not serum IgG (P = 0.21). In conclusion, a single oral dose of dmLT was well tolerated and immunogenic, with immune responses plateauing at the 50-μg dose. (This clinical trial is registered at www.clinicaltrials.gov, registration number NCT01147445.).
Department of Epidemiology and Public Health.
Samer S
SS
El-Kamary
Mitchell B
MB
Cohen
A Louis
AL
Bourgeois
Lillian
L
Van De Verg
Nicole
N
Bauers
Mardi
M
Reymann
Marcela F
MF
Pasetti
Wilbur H
WH
Chen
D000284:Administration, Oral; D000328:Adult; D000907:Antibodies, Bacterial / Q000032:analysis / Q000097:blood; D000921:Antibody-Producing Cells / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D054307:Enterotoxigenic Escherichia coli / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000276:immunology*; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D005243:Feces / Q000737:chemistry; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis / Q000097:blood; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D008297:Male; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C027538:heat-labile enterotoxin, E coli