Molecular bases of protective immune responses against botulinum neurotoxin A--how antitoxin antibodies block its action

Critical Reviews in Immunology
M Z AtassiK Roger Aoki

Abstract

In studies from this laboratory, we localized the regions on the H chain of botulinum neurotoxin A (BoNT/A) that are recognized by anti-BoNT/A antibodies (Abs) and block the activity of the toxin in vivo. These Abs were obtained from cervical dystonia patients who had been treated with BoNT/A and had become unresponsive to the treatment, as well as blocking Abs raised in mouse, horse, and chicken. We also localized the regions involved in BoNT/A binding to mouse brain synaptosomes (snp). Comparison of spatial proximities in the three-dimensional structure of the Ab-binding regions and the snp binding showed that except for one, the Ab-binding regions either coincide or overlap with the snp regions. It should be folly expected that protective Abs when bound to the toxin at sites that coincide or overlap with snp binding would prevent the toxin from binding to nerve synapse and therefore block toxin entry into the neuron. Thus, analysis of the locations of the Ab-binding and the snp-binding regions provides a molecular rationale for the ability of protecting Abs to block BoNT/A action in vivo.

Citations

Apr 7, 2015·Expert Opinion on Therapeutic Patents·Christopher D KaneSina Bavari
Sep 25, 2010·Scandinavian Journal of Medicine & Science in Sports·D M Wiese-Bjornstal
Mar 17, 2009·Toxicon : Official Journal of the International Society on Toxinology·M Zouhair Atassi

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