title: Mouse in vivo neutralization of Escherichia coli Shiga toxin 2 with monoclonal antibodies.
abstract: Shiga toxin-producing Escherichia coli (STEC) food contaminations pose serious health concerns, and have been the subject of massive food recalls. STEC has been identified as the major cause of the life-threatening complication of hemolytic uremic syndrome (HUS). Besides supportive care, there currently are no therapeutics available. The use of antibiotics for combating pathogenic E. coli is not recommended because they have been shown to stimulate toxin production. Clearing Stx2 from the circulation could potentially lessen disease severity. In this study, we tested the in vivo neutralization of Stx2 in mice using monoclonal antibodies (mAbs). We measured the biologic half-life of Stx2 in mice and determined the distribution phase or t(1/2) α to be 3 min and the clearance phase or t(1/2) β to be 40 min. Neutralizing mAbs were capable of clearing Stx2 completely from intoxicated mouse blood within minutes. We also examined the persistence of these mAbs over time and showed that complete protection could be passively conferred to mice 4 weeks before exposure to Stx2. The advent of better diagnositic methods and the availability of a greater arsenal of therapeutic mAbs against Stx2 would greatly enhance treatment outcomes of life threatening E. coli infections.
authors.affiliation: Western Regional Research Center, U.S. Department of Agriculture, Agricultural Research Service, 800 Buchanan Street, Albany, CA 94710, USA. xiaohua.he@ars.usda.gov.
authors.forename: Luisa W
authors.initials: LW
authors.lastname: Cheng
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Henderson
authors.forename: Stephanie
authors.initials: S
authors.lastname: Patfield
authors.forename: Larry H
authors.initials: LH
authors.lastname: Stanker
authors.forename: Xiaohua
authors.initials: X
authors.lastname: He
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004927:Escherichia coli Infections / Q000175:diagnosis; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000517:prevention & control; D051379:Mice; D022641:Shiga Toxin 2 / Q000097:blood* / Q000493:pharmacokinetics / Q000633:toxicity*; D054323:Shiga-Toxigenic Escherichia coli / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D022641:Shiga Toxin 2