title: Diagnostic and possible therapeutic application of a monoclonal antibody (14G8) directed against botulinum type C neurotoxin.
abstract: A monoclonal antibody, designated 14G8, detected Clostridium botulinum type C neurotoxin in immunoassays requiring native confirmation of the analyte. 14G8 bound to the light chain of the type C neurotoxin, which is conserved between strains of C. botulinum type C and C/d mosaic neurotoxins. 14G8 did not react to any other serotypes of C. botulinum neurotoxins. In mouse phrenic nerve-hemidiaphragm assays, 14G8, when combined with a second antibody (5D9-H9-A9, which reacts to epitopes on the carboxy terminus of the heavy chain), was able to protect the mouse myoneural junction from intoxication with C. botulinum type C neurotoxin. When used individually, both 14G8 and 5D9-H9-G9 antibodies slowed the loss of twitch tension in the mouse phrenic nerve-hemidiaphragm assays, but did not completely protect the phrenic nerve from paralysis. In in vivo mouse botulinum neurotoxin type C challenge studies, the combination of 14G8 and 5D9-H9-A9 significantly increased mean time-to-death and survival when compared to toxin controls and mice receiving only one of the monoclonal antibodies. These results suggest that the 14G8 monoclonal antibody could have useful therapeutic applications.
authors.affiliation: Division of Integrated Toxicology, U.S. Army Research Institute of Infectious Diseases, Frederick, Maryland 21702, USA. vicki.montgomery@amedd.army.mil
authors.forename: Vicki A
authors.initials: VA
authors.lastname: Montgomery
authors.forename: Leonard A
authors.initials: LA
authors.lastname: Smith
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism* / Q000627:therapeutic use; D000918:Antibody Specificity; D015153:Blotting, Western; D001905:Botulinum Toxins / Q000276:immunology / Q000378:metabolism*; D003964:Diaphragm / Q000294:innervation / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D008807:Mice, Inbred BALB C; D009469:Neuromuscular Junction / Q000378:metabolism*; D010791:Phrenic Nerve / Q000166:cytology / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D001905:Botulinum Toxins; C096324:botulinum toxin type C