Prevention and treatment of Clostridium perfringens epsilon toxin intoxication in mice with a neutralizing monoclonal antibody (c4D7) produced in Nicotiana benthamiana

J. P. Garcia, J. Beingesser, O. Bohorov, N. Bohorova, C. Goodman, D. Kim, M. Pauly, J. Velasco, K. Whaley, L. Zeitlin, C. J. Roy, Francisco A Uzal

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Epsilon toxin (ETX), produced by Clostridium perfringens types B and D, is among the most lethal toxins known. ETX is a potential bioterrorism threat that was listed as a Category B agent by the U.S. Centers for Disease Control until 2012 and it still remains a toxin of interest for several government agencies. We produced a monoclonal antibody (MAb) against ETX (ETX MAb c4D7) in Nicotiana benthamiana and characterized its preventive and therapeutic efficacy in mice. The ETX preparation used was highly lethal for mice (LD50 = 1.6 μg/kg) and resulted in a mean time from inoculation to death of 18 and 180 min when administered intravenously or intraperitoneally, respectively. High lethal challenge resulted in dramatic increases of a variety of pro-inflammatory cytokines in serum, while lower, but still lethal doses, did not elicit such responses. ETX MAb c4D7 was highly effective prophylactically (ED50 = 0.3 mg/kg; ED100 = 0.8 mg/kg) and also provided protection when delivered 15-30 min post-ETX intoxication. These data suggest that ETX MAb c4D7 may have use as a pre- and post-exposure treatment for ETX intoxication.

Original languageEnglish (US)
Pages (from-to)93-98
Number of pages6
JournalToxicon
Volume88
DOIs
StatePublished - Sep 15 2014

Keywords

  • Epsilon toxin
  • Monoclonal antibody
  • Nicotiana benthamiana
  • Preventive
  • Therapeutic

ASJC Scopus subject areas

  • Toxicology

Fingerprint Dive into the research topics of 'Prevention and treatment of Clostridium perfringens epsilon toxin intoxication in mice with a neutralizing monoclonal antibody (c4D7) produced in Nicotiana benthamiana'. Together they form a unique fingerprint.

Cite this