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ISSN Print: 1040-8401
ISSN Online: 2162-6472
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Molecular Bases of Protective Immune Responses against BotuIInum Neurotoxin AHow Antitoxin Antibodies Block Its Action
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.
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Atassi M. Zouhair, Immune recognition of BoNTs A and B: How anti-toxin antibodies that bind to the heavy chain obstruct toxin action, Toxicon, 54, 5, 2009. Crossref
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Dolimbek Behzod Z., Aoki K. Roger, Atassi M. Zouhair, Reduction of antibody response against botulinum neurotoxin A by synthetic monomethoxypolyethylene glycol–peptide conjugates, Immunology Letters, 137, 1-2, 2011. Crossref
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Atassi M.Z., Molecular basis of immunogenicity to botulinum neurotoxins and uses of the defined antigenic regions, Toxicon, 107, 2015. Crossref
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Kane Christopher D, Nuss Jonathan E, Bavari Sina, Novel therapeutic uses and formulations of botulinum neurotoxins: a patent review (2012 – 2014), Expert Opinion on Therapeutic Patents, 25, 6, 2015. Crossref
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Pickett Andy, Botulinum Toxin as a Clinical Product: Manufacture and Pharmacology, in Clinical Applications of Botulinum Neurotoxin, 2014. Crossref
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Li Zhen, Lu Jiansheng, Tan Xiao, Wang Rong, Xu Qing, Yu Yunzhou, Yang Zhixin, Functional EL-HN Fragment as a Potent Candidate Vaccine for the Prevention of Botulinum Neurotoxin Serotype E, Toxins, 14, 2, 2022. Crossref
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Uibel Stefanie, Groneberg David A., Clostridium botulinum und seine Toxine: Krankheitserreger und potentielle Biowaffe?, Zentralblatt für Arbeitsmedizin, Arbeitsschutz und Ergonomie, 61, 4, 2011. Crossref