title: Prevention and treatment of Clostridium perfringens epsilon toxin intoxication in mice with a neutralizing monoclonal antibody (c4D7) produced in Nicotiana benthamiana.
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.
authors.affiliation: California Animal Health and Food Safety Laboratory System, San Bernardino Branch, School of Veterinary Medicine, University of California, Davis, San Bernardino, CA 92408, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Garcia
authors.affiliation: California Animal Health and Food Safety Laboratory System, San Bernardino Branch, School of Veterinary Medicine, University of California, Davis, San Bernardino, CA 92408, USA.
authors.forename: J
authors.initials: J
authors.lastname: Beingesser
authors.affiliation: Mapp Biopharmaceutical, Inc., San Diego, CA, USA.
authors.forename: O
authors.initials: O
authors.lastname: Bohorov
authors.affiliation: Mapp Biopharmaceutical, Inc., San Diego, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Bohorova
authors.affiliation: Mapp Biopharmaceutical, Inc., San Diego, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Goodman
authors.affiliation: Mapp Biopharmaceutical, Inc., San Diego, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Kim
authors.affiliation: Mapp Biopharmaceutical, Inc., San Diego, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Pauly
authors.affiliation: Mapp Biopharmaceutical, Inc., San Diego, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Velasco
authors.affiliation: Mapp Biopharmaceutical, Inc., San Diego, CA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Whaley
authors.affiliation: Mapp Biopharmaceutical, Inc., San Diego, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zeitlin
authors.affiliation: Microbiology Division, Tulane National Primate Research Center, Covington, LA, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Roy
authors.affiliation: California Animal Health and Food Safety Laboratory System, San Bernardino Branch, School of Veterinary Medicine, University of California, Davis, San Bernardino, CA 92408, USA. Electronic address: fuzal@cahfs.ucdavis.edu.
authors.forename: F A
authors.initials: FA
authors.lastname: Uzal
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D001427:Bacterial Toxins / Q000276:immunology / Q000506:poisoning*; D016207:Cytokines / Q000097:blood; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014026:Nicotiana / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D001427:Bacterial Toxins; C039811:Clostridium perfringens epsilon-toxin; D016207:Cytokines
keywords: Epsilon toxin; Monoclonal antibody; Nicotiana benthamiana; Preventive; Therapeutic