A Human Monoclonal Antibody that Binds Serotype A Botulinum Neurotoxin

摘要

Monoclonal antibodies have demonstrated significant potential as therapeutics for botulinum neurotoxin exposures.nWe previously described a hybridoma method for cloning native human antibodies that uses a murinenmyeloma cell line that ectopically expresses the human telomerase catalytic subunit gene (hTERT) and thenmurine interleukin-6 gene (mIL-6). Here we describe a heterohybridoma cell line that ectopically expressesnmIL-6 and hTERT and has improved stability of hTERT expression. We fused this cell line to human peripheralnblood B cells from a subject who had received the botulinum toxoid vaccine, cloning a high-affinitynantibody (13A) specific for serotype A botulinum neurotoxin (BoNT/A). The 13A antibody is an affinity-matured,npost-germinal center IgG1 lambda antibody that has partial neutralization activity in vivo. 13A bindsnan epitope on BoNT/A that overlaps the binding epitope of an IgG antibody previously shown to fully neutralizena lethal dose of BoNT/A in vivo. The 13A antibody may be useful for diagnostic testing or for incorporationninto an oligoclonal therapeutic to counteract BoNT/A exposure.