title: Transcutaneous immunization with the heat-labile toxin (LT) of enterotoxigenic Escherichia coli (ETEC): protective efficacy in a double-blind, placebo-controlled challenge study.
abstract: BACKGROUND
  An enterotoxigenic Escherichia coli (ETEC) vaccine could reduce diarrhea among children in developing countries and travelers to these countries. The heat-labile toxin (LT) of ETEC is immunogenic but too toxic for oral or nasal vaccines.
  
  
  METHODS
  In a double-blind, placebo-controlled trial, 59 adults were randomized to receive 50 microg of LT or placebo in a patch applied to alternating arms on days 0, 21, and 42. On day 56, 27 vaccinees and 20 controls were challenged orally with 6x10(8) cfu of LT+/ST+ ETEC.
  
  
  RESULTS
  100 and 97% of vaccinees had 4-fold increases in anti-LT IgG and IgA, and 100 and 90% developed IgG- and IgA-antibody-secreting cell responses. The study did not meet the primary endpoint: 82% of vaccinees and 75% of controls had moderate to severe ETEC illness. However, vaccinees with ETEC illness had lower numbers (6.8 versus 9.7, p=0.04) and weights of loose stools (840 g versus 1147 g, p<0.05), a decreased need for intravenous fluids (14% versus 40%, p=0.03) and a delayed onset of diarrhea (30 h versus 22 h, p=0.01).
  
  
  CONCLUSIONS
  Transcutaneous LT vaccination induced anti-toxin immune responses that did not prevent but mitigated illness following a high-dose challenge with a virulent LT+/ST+ ETEC strain.
authors.affiliation: Division of Infectious Diseases, Johns Hopkins University, Johns Hopkins Bayview Medical Center, 4940 Eastern Ave., Baltimore, MD 21224, United States. rmckenz@jhmi.edu
authors.forename: Robin
authors.initials: R
authors.lastname: McKenzie
authors.forename: A Louis
authors.initials: AL
authors.lastname: Bourgeois
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Frech
authors.forename: David C
authors.initials: DC
authors.lastname: Flyer
authors.forename: Arlene
authors.initials: A
authors.lastname: Bloom
authors.forename: Kazem
authors.initials: K
authors.lastname: Kazempour
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Glenn
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D003967:Diarrhea / Q000382:microbiology / Q000517:prevention & control; D004311:Double-Blind Method; D004768:Enterotoxins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology* / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000382:microbiology / Q000517:prevention & control*; D029968:Escherichia coli Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D006801:Humans; D007114:Immunization; D007070:Immunoglobulin A / Q000032:analysis; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; D007070:Immunoglobulin A; C027538:heat-labile enterotoxin, E coli