Deciphering antibody properties that lead to potent botulinum neurotoxin neutralization

Abstract

Monoclonal antibodies (mAbs) have been developed that bind to the toxin binding domain (H_C) of botulinum toxin type A. These mAbs recognize with high affinity nonoverlapping epitopes on native toxin. The potency of a combination of three of the mAbs is almost 100 times greater than that reported for human polyclonal botulinum immune globulin. Potency appears to result largely from a marked increase in binding affinity for toxin that results when antibodies are combined. Precise epitope, or even domain recognized, seems to be of much less importance. The very high affinity required for toxin neutralization suggests why single mAbs that potently neutralize toxin have not been reported. Such affinities are not typically generated by the immune response. © 2004 Movement Disorder Society