1. Prophylactic Efficacy of Hyperimmune Bovine Colostral Antiadhesin Antibodies Against Enterotoxigenic Escherichia coli Diarrhea: A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Trial.
- Author
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Savarino, Stephen J., McKenzie, Robin, Tribble, David R., Porter, Chad K., O'Dowd, Aisling, Cantrell, Joyce A., Sincock, Stephanie A., Poole, Steven T., DeNearing, Barbara, Woods, Colleen M., Hye Kim, Grahek, Shannon L., Brinkley, Carl, Crabb, Joseph H., Bourgeois, A. Louis, and Kim, Hye
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IMMUNOGLOBULINS , *ENTEROBACTERIACEAE , *SUMMER diseases , *INTESTINAL diseases , *PHYSICAL education for the blind , *DEAFBLIND people , *CELL metabolism , *THERAPEUTIC use of immunoglobulins , *BACTERIAL antibodies , *ANIMAL experimentation , *BACTERIAL antigens , *BACTERIAL growth , *CATTLE , *CELLS , *COLOSTRUM , *COMPARATIVE studies , *DIARRHEA , *ESCHERICHIA coli , *ESCHERICHIA coli diseases , *RESEARCH methodology , *MEDICAL cooperation , *MEMBRANE proteins , *MICROBIOLOGICAL techniques , *ORAL drug administration , *RESEARCH , *EVALUATION research , *RANDOMIZED controlled trials , *BLIND experiment , *THERAPEUTICS ,RESEARCH evaluation - Abstract
Background: Tip-localized adhesive proteins of bacterial fimbriae from diverse pathogens confer protection in animal models, but efficacy in humans has not been reported. Enterotoxigenic Escherichia coli (ETEC) commonly elaborate colonization factors comprising a minor tip adhesin and major stalk-forming subunit. We assessed the efficacy of antiadhesin bovine colostral IgG (bIgG) antibodies against ETEC challenge in volunteers.Methods: Adults were randomly assigned (1:1:1) to take oral hyperimmune bIgG raised against CFA/I minor pilin subunit (CfaE) tip adhesin or colonization factor I (CFA/I) fimbraie (positive control) or placebo. Two days before challenge, volunteers began a thrice-daily, 7-day course of investigational product administered in sodium bicarbonate 15 minutes after each meal. On day 3, subjects drank 1 × 109 colony-forming units of colonization factor I (CFA/I)-ETEC strain H10407 with buffer. The primary efficacy endpoint was diarrhea within 120 hours of challenge.Results: After enrollment and randomization, 31 volunteers received product, underwent ETEC challenge, and were included in the per protocol efficacy analysis. Nine of 11 placebos developed diarrhea, 7 experiencing moderate to severe disease. Protective efficacy of 63% (P = .03) and 88% (P = .002) was observed in the antiadhesin bIgG and positive control groups, respectively.Conclusions: Oral administration of anti-CFA/I minor pilin subunit (CfaE) antibodies conferred significant protection against ETEC, providing the first clinical evidence that fimbrial tip adhesins function as protective antigens. [ABSTRACT FROM AUTHOR]- Published
- 2017
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