Efficacy of Urtoxazumab (TMA-15 Humanized Monoclonal Antibody Specific for Shiga Toxin 2) Against Post-Diarrheal Neurological Sequelae Caused by Escherichia coli O157:H7 Infection in the Neonatal Gnotobiotic Piglet Model

Authors

Rodney A. Moxley, University of Nebraska - LincolnFollow
David H. Francis, South Dakota State UniversityFollow
Mizuho Tamura, Teijin Pharma LimitedFollow
David B. Marx, University of Nebraska-LincolnFollow
Kristina Santiago-Mateo, Canadian Food Inspection AgencyFollow
Mojun Zhao, Valley Pathologists, Inc.Follow

Date of this Version

2017

Citation

Toxins 2017, 9, 49; doi:10.3390/toxins9020049.

Comments

Copyright © 2017, the authors. Licensee MDPI, Basel, Switzerland. Open access, Creative Commons Attribution license 4.0.

Abstract

Enterohemorrhagic Escherichia coli (EHEC) is the most common cause of hemorrhagic colitis and hemolytic uremic syndrome in human patients, with brain damage and dysfunction the main cause of acute death. We evaluated the efficacy of urtoxazumab (TMA-15, Teijin Pharma Limited), a humanized monoclonal antibody against Shiga toxin (Stx) 2 for the prevention of brain damage, dysfunction, and death in a piglet EHEC infection model. Forty-five neonatal gnotobiotic piglets were inoculated orally with 3 x 10⁹ colony-forming units of EHEC O157:H7 strain EDL933 (Stx1⁺, Stx2⁺) when 22–24 h old. At 24 h post-inoculation, piglets were intraperitoneally administered placebo or TMA-15 (0.3, 1.0 or 3.0 mg/kg body weight). Compared to placebo (n = 10), TMA-15 (n = 35) yielded a significantly greater probability of survival, length of survival, and weight gain (p