Diagnostic and Possible Therapeutic Application of a Monoclonal Antibody (14G8) Directed Against botulinum Type C Neurotoxin

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.