MI010-06 Egg-Derived Antibody to E. coli Heat Stable Enterotoxin - Completed

Antimicrobials are still the major tools for treating many infectious diseases.  However,
the emergence of multidrug resistant bacterial pathogens and the observation that antibiotic treatment might actually icnrease the produciton of some bacterial-derived toxins, limit the usefulness of this therapeutic approach.  moreover, the fact that several bacterial agents cause diarrheal diseases through non-immunogenic toxins complicates the treatment of these diseases.  An example is the Enterotoxigenic Escherichia coli, (ETEC) strains that produce heat stable enterotoxin (STa) and are a common cause of acute watery diarrhea, which results in rapid dehydration,  and traveler’s diarrhea, the leading bacterial cause of outbreaks of gastroenteritis on cruise ships, and also the cause of acute watery diarrhea, which results in rapid dehydration and death in human neonates.  STa-producing ETEC are highly virulent and the protein toxin, in contrast to heat labile enterotoxin (Lt), is poorly immunogenic in humans.  Due to the phylogenetic differences between the avian and mammalian species, the immune response increases when a bird is immunized with certain immunogens from a different source.  Therefore, we propose that chickens are more promising candidate animals for producing high titer antibodies against ST than rabbits and other mammalian species.  As a model for this novel approach, we intend to purify ETEC-STa and immunize egg-laying hens to produce a highly specific egg yolk-derived antibody in partnership with Dr. Marcela Pasetti from the Maryland Immunology Research Unit.  The proposed immunotherapeutic reagent will be characterized for levels of antibody and avidity, as well as evaluated for its neutralization capacity against the toxin using an established mouse assay.

Publicatiions:

Interaction of Escherichia coli heat-stable enterotoxin(STa) with its putative receptoron the intestinal tract of newborn kids