Development of novel human monoclonal antibodies for botulinum neurotoxin type F subtype 1

Different types of Botulinum neurotoxins (BoNTs) cause human botulism. Among them, type F botulism, caused by genetically diverse BoNT/F subtypes, is rare and may be overlooked despite its clinical importance. Toxin-neutralizing human antibodies, which carry the minimum risks of inducing serum sickness or anaphylaxis, are ideal for the treatment of human botulism. In this study, we generated human monoclonal antibodies (mAb) against BoNT/F using trans-chromosomic monoclonal antibody (TC-mAb) mice. A recombinant toxin fragment consisting of the light chain and the heavy chain N-terminal domain (L-H_N) of BoNT/F subtype 1 was selected as the antigen because this subtype is used as the reference antigen for currently available antitoxin preparations. Three mAbs (126, 134, and 146) were obtained and reconstructed in a human IgG format. Although the mAbs did not significantly inhibit VAMP2 cleavage in primary cultured neurons, they exhibited partial neutralizing activities in mouse bioassays. In addition, we found that the combinatorial use of 126 and 146 enhanced neutralizing activity. These findings provide important information for the future development of human therapeutic mAbs against BoNT/F.