Journal Article

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

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

2007

Overview

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. 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 × 10 8 cfu of LT +/ST + ETEC. 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). 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.

• Publisher: Elsevier Ltd,Elsevier
• Subject: Administration, Cutaneous / Adolescent / Adult / Allergy and Immunology / Antibodies, Bacterial - blood / Applied microbiology / Bacterial Toxins - administration & dosage / Bacterial Toxins - adverse effects / Bacterial Toxins - immunology / Bacteriology / Biological and medical sciences / Diarrhea / Diarrhea - microbiology / Diarrhea - prevention & control / Double-Blind Method / Enterotoxigenic E. coli / Enterotoxins - administration & dosage / Enterotoxins - adverse effects / Enterotoxins - immunology / Escherichia coli / Escherichia coli - immunology / Escherichia coli - pathogenicity / Escherichia coli Infections - microbiology / Escherichia coli Infections - prevention & control / Escherichia coli Proteins - administration & dosage / Escherichia coli Proteins - adverse effects / Escherichia coli Proteins - immunology / Escherichia coli Vaccines - administration & dosage / Escherichia coli Vaccines - adverse effects / Escherichia coli Vaccines - immunology / Feces - chemistry / Feces - microbiology / Fundamental and applied biological sciences. Psychology / Humans / Immunization / Immunoglobulin A - analysis / Microbiology / Middle Aged / Miscellaneous / Transcutaneous immunization / Treatment Outcome / Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)