A new neutralizing antibody against botulinum neurotoxin B recognizes the protein receptor binding sites for synaptotagmins II

Microbes and Infection
Hui WangXiang Gao

Abstract

Botulinum neurotoxins (BoNts) pose a biological hazard to humans and a serious potential bioweapon threat. Given the safety concern regarding the currently used equine antitoxin therapy for botulism, it is imperative to develop agents that are effective binding inhibitors. The aim of this study was to identify a novel neutralizing antibody against botulinum neurotoxin B (BoNtb) that recognizes the protein receptor binding sites for synaptotagmins II. This antibody showed significant dose-dependent protection against lethal toxin challenge in vivo at an intraperitoneal (i.p.) dose 10 times the half lethal dose (LD50). We proved that the efficacy of SC12 was based on its counteraction on the recognition and binding of BoNtb to target cells, resulting from the combination of antibody with the high affinity (KD: 1.34 nM) to protein receptor binding sites of BoNt by targeting a 25-mer dominant antigenic site on Hcc region (residues 1253-1277). The structure of the site targeted by this antibody overlaps the pocket-like protein receptor binding sites located at the distal tip of toxin molecule. Information gained from this study will facilitate the development of potent inhibitors that prevent the binding of BoNts with its receptors.

References

Oct 12, 2001·Toxicon : Official Journal of the International Society on Toxinology·E A Johnson, M Bradshaw
Aug 7, 2002·Revista Do Instituto De Medicina Tropical De São Paulo·Juliano BordignonCarlos Roberto Zanetti
Jun 10, 2003·Journal of Applied Toxicology : JAT·Brian M Paddle
Sep 25, 2003·The Journal of Cell Biology·Min DongEdwin R Chapman
Oct 7, 2004·Proceedings of the National Academy of Sciences of the United States of America·Min DongEdwin R Chapman
Oct 7, 2004·The Journal of Biological Chemistry·Diana R LazzellRoger Janz
Mar 26, 2005·Current Medicinal Chemistry·Rickey P HicksDonald R Skillman
Apr 2, 2005·Nature Reviews. Drug Discovery·James C BurnettSina Bavari
May 24, 2005·Current Opinion in Pharmacology·Cesare Montecucco, Jordi Molgó
Aug 23, 2005·Journal of the American Academy of Dermatology·Timothy R CotéM Miles Braun
Sep 7, 2005·Protein Expression and Purification·Sapna SharmaBal Ram Singh
Jan 26, 2006·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·Christine M ChengRosalie P Patel
Mar 18, 2006·Science·Min DongEdwin R Chapman
Feb 22, 2007·Biochemistry·Michael R Baldwin, Joseph T Barbieri
Sep 1, 2007·Chembiochem : a European Journal of Chemical Biology·Brett HelmsE W Meijer
Sep 21, 2007·The Journal of Allergy and Clinical Immunology·Chunsheng JinFriedrich Altmann

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