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

Toxicon. 2014 Sep;88:93-8. doi: 10.1016/j.toxicon.2014.06.012. Epub 2014 Jun 17.

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.

Keywords: Epsilon toxin; Monoclonal antibody; Nicotiana benthamiana; Preventive; Therapeutic.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Neutralizing / therapeutic use*
  • Bacterial Toxins / immunology
  • Bacterial Toxins / poisoning*
  • Cytokines / blood
  • Female
  • Lethal Dose 50
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Tobacco / genetics*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Bacterial Toxins
  • Clostridium perfringens epsilon-toxin
  • Cytokines