State Key Laboratory of Pathogens and Biosecurity, Institute of Microbiology and Epidemiology, No.20 Dongdajie, Fengtai District, Beijing 100071, PR China.
Microbes Infect. 2010 Nov;12(12-13):1012-8. doi: 10.1016/j.micinf.2010.07.002. Epub 2010 Aug 1.
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.
肉毒梭菌神经毒素（BoNTs）对人类构成生物危害，也是一种严重的潜在生物武器威胁。鉴于目前用于肉毒中毒的马抗毒素治疗存在安全问题，开发有效的结合抑制剂迫在眉睫。本研究旨在鉴定一种针对肉毒神经毒素 B（BoNtb）的新型中和抗体，该抗体识别与突触结合蛋白 II 结合的蛋白质受体结合位点。该抗体在腹腔内（i.p.）剂量为半致死剂量（LD50）的 10 倍时，对致死毒素攻击表现出显著的剂量依赖性保护作用。我们证明，SC12 的功效基于其对 BoNtb 与靶细胞识别和结合的拮抗作用，这是由于抗体与 BoNt 蛋白受体结合位点的高亲和力（KD：1.34 nM）结合所致，该抗体针对 Hcc 区域（残基 1253-1277）上的 25 个氨基酸优势抗原位点。该抗体靶向的位点结构与位于毒素分子远端尖端的类似口袋的蛋白质受体结合位点重叠。这项研究获得的信息将有助于开发有效的抑制剂，防止 BoNTs 与其受体结合。
