title: A double-blind, placebo-controlled trial to evaluate the efficacy of PTL-003, an attenuated enterotoxigenic E. coli (ETEC) vaccine strain, in protecting against challenge with virulent ETEC.
abstract: Enterotoxigenic E. coli (ETEC) are an important cause of diarrhea in developing countries, especially among indigenous children and travelers. In this randomized, double-blind, placebo-controlled trial, a live, attenuated CS1/CS3 ETEC strain, PTL-003, was tested as a potential vaccine strain. Thirty-three subjects drank buffered solutions containing either PTL-003 or placebo on Days 0 and 10 and were challenged with virulent CS1/CS3 ETEC strain E24377A on Day 28. The vaccine did not protect against moderate to severe ETEC illness (the primary endpoint), but it did prime subjects for a rapid antibody response to CS1 and CS3 after challenge, suggesting that a dose of vaccine on Day 28 might improve the immune response to the vaccine. Higher serum anti-CS3 IgA titers at the time of challenge correlated with less severe diarrheal illness.
authors.affiliation: Division of Infectious Diseases, Johns Hopkins University, Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, Baltimore, MD 21224, United States. rmckenz@jhmi.edu
authors.forename: Robin
authors.initials: R
authors.lastname: McKenzie
authors.forename: Michael
authors.initials: M
authors.lastname: Darsley
authors.forename: Nicola
authors.initials: N
authors.lastname: Thomas
authors.forename: Roger
authors.initials: R
authors.lastname: Randall
authors.forename: Colleen
authors.initials: C
authors.lastname: Carpenter
authors.forename: Edrick
authors.initials: E
authors.lastname: Forbes
authors.forename: Mariel
authors.initials: M
authors.lastname: Finucane
authors.forename: R Bradley
authors.initials: RB
authors.lastname: Sack
authors.forename: Eric
authors.initials: E
authors.lastname: Hall
authors.forename: August L
authors.initials: AL
authors.lastname: Bourgeois
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D003906:Developing Countries; D003967:Diarrhea / Q000517:prevention & control; D004311:Double-Blind Method; D054307:Enterotoxigenic Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000517:prevention & control*; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D012720:Severity of Illness Index; D013223:Statistics as Topic; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D022361:Escherichia coli Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010919:Placebos; D014613:Vaccines, Attenuated