Deciphering antibody properties that lead to potent botulinum neurotoxin neutralization.
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.
Marks
James D
JD
Department of Anesthesia and Pharmaceutical Chemistry, University of California, San Francisco General Hospital, San Francisco, California 94110, USA. marksj@anesthesia.ucsf.edu
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions / Q000502:physiology*; D019274:Botulinum Toxins, Type A / Q000276:immunology* / Q000494:pharmacology; D001906:Botulism / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018604:Epitope Mapping; D006801:Humans; D007928:Lethal Dose 50; D009465:Neuromuscular Agents / Q000276:immunology* / Q000494:pharmacology; D009498:Neurotoxins / Q000378:metabolism; D009500:Neutralization Tests / Q000379:methods
D000911:Antibodies, Monoclonal; D009465:Neuromuscular Agents; D009498:Neurotoxins; D019274:Botulinum Toxins, Type A