Transcutaneous immunization with the heat-labile toxin (LT) of enterotoxigenic Escherichia coli (ETEC): Protective efficacy in a double-blind, placebo-controlled challenge study

Robin McKenzie, A. Louis Bourgeois, Sarah A. Frech, David C. Flyer, Arlene Bloom, Kazem Kazempour, Gregory M. Glenn

Research output: Contribution to journalArticle

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 μg 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 6 × 108 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.

Original languageEnglish (US)
Pages (from-to)3684-3691
Number of pages8
JournalVaccine
Volume25
Issue number18
DOIs
StatePublished - May 4 2007

Keywords

  • Diarrhea
  • Enterotoxigenic E. coli
  • Transcutaneous immunization

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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