Research Project
2148351
E. coli Ol57:H7 is an emerging food-borne pathogen with substantial morbidity and mortality. There are an estimated 20,000 cases of E. coli 0157:H7 infection per year in the United States. However, only 11 states require reporting of the cases to the State Health Department; hence, the actual number of cases is likely to be much higher. Twenty-two percent of children acquiring E. coli Ol57:H7 infection develop potentially fatal complications, such as hemolytic uremic syndrome (HUS). Patients who develop complications must be hospitalized for long periods, and often require life-long kidney dialysis or kidney transplants. HUS is believed to be caused by verotoxins produced by the offending bacterium, and there are no antitoxins available for clinical use. Ophidian Pharmaceuticals herein proposes to develop E. coli Ol57:H7 antiverotoxin using proprietary methods for the large-scale production of therapeutic polyclonal antibodies from eggs of hyperimmune hens. High-purity avian antitoxins have been shown to have superior toxin- neutralizing potency when used in either a parenteral or enteral dosing regimen. Hens will be immunized with pure E. coli O157:H7 verotoxins, followed by preparation of yolk immunoglobulin fractions. The resulting antibodies will be characterized in vitro by immunochemical analysis and by toxin neutralization in a vero cell assay. The therapeutic efficacy of antiverotoxin will be assessed in vivo in a mouse HUS model using either enteral or parenteral antiverotoxin administration. These studies will i) provide experimental evidence for the therapeutic utility of antiverotoxin antibodies in E. coli O157:H7 disease, such as HUS, and ii) determine if disease progression can be arrested by antiverotoxin enterally administered and/or whether antiverotoxin is effective when given parenterally.
