Submitted to: Infection and Immunity
Publication Type: Peer reviewed journal
Publication Acceptance Date: 10/11/2013
Publication Date: 10/22/2013
Publication URL: http://handle.nal.usda.gov/10113/59076
Citation: Cheng, L.W., Henderson II, T.D., Patfield, S.A., Stanker, L.H., He, X. 2013. Mouse in vivo neutralization of Escherichia coli Shiga toxin 2 with monoclonal antibodies. Infection and Immunity. 5:1845-1858. DOI: 10.3390/toxins5101845. Interpretive Summary: Shiga toxin (Stx)-producing Escherichia coli (STEC) are frequent causes of severe human diseases ranging from bloody diarrhea to life-threatening hemolytic uremic syndrome (HUS). Shiga toxin 2 (Stx2) is the primary virulence factor of STEC. Currently there are no specific protective measures against STEC infection other than supportive therapy. This manuscript investigated the effects of monoclonal antibodies (mAbs) on neutralization of Stx2 in mice. Our results indicate that the three mAbs produced in our laboratory are good candidates for antibody-based therapy against Stx2-associated HUS.
Technical Abstract: Escherichia coli (E. coli) food contaminations pose serious health and food safety concerns, and have been the subject of massive food recalls. Shiga toxin 2 (Stx2)-producing E. coli has been identified as the major cause of hemorrhagic colitis and hemolytic uremic syndrome (HUS), the most severe disease manifestations. Besides supportive care, there are currently no therapeutics available. The use of antibiotics for combating pathogenic E. coli is not recommended because they have been shown to stimulate toxin production. Thus, 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 t1/2 a to be 3 min and the clearance phase or t1/2 ß to be 40 min. Neutralizing mAbs were capable of clearing Stx2 completely from intoxicated mice blood within minutes. We also examined the persistence of these mAbs over time and showed that complete protection could be passively conferred to mice at least 4 weeks before exposure to Stx2. The advent of better diagnosis methods and the availability of a greater arsenal of therapeutic mAbs against Stx2 would greatly enhance treatment outcomes of life threatening E. coli infections.