Journal Article

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

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

2007

Overview

Background An enterotoxigenicEscherichia 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 50μg 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 6x108cfu 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 (840g versus 1147g,p<0.05), a decreased need for intravenous fluids (14% versus 40%,p=0.03) and a delayed onset of diarrhea (30h versus 22h,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.

• Publisher: Elsevier Limited
• Subject: Antibiotics / Antitoxins / Developing countries / Diarrhea / E coli / Family medical history / Hepatitis / Illnesses / Immunization / Laboratories / LDCs / Studies / Toxins / Tropical diseases / Vaccines