Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Department of Laboratory Medicine, School of Allied Medical Sciences, Kashan University of Medical Sciences, Kashan, Iran.
Neurotox Res. 2020 Feb;37(2):239-249. doi: 10.1007/s12640-019-00096-w. Epub 2019 Aug 13.
Tetanus as a life-threatening disease is characterized by muscle spasm. The disease is caused by the neurotoxin of Clostridium tetani. Active form of tetanus neurotoxin is composed of the light chain (fragment A) and the heavy chain. Fragment A is a zinc metalloprotease, which cleaves the neuronal soluble N-ethylmaleimide-sensitive attachment receptor (SNARE) protein, leading to the blockade of inhibitory neurotransmitter release and subsequent generalized muscular spasm. Two functional domains of the heavy chain are fragment C, which is required for neuronal cell binding of the toxin and subsequent endocytosis into the vesicles, and fragment B, which is important for fragment A translocation across the vesicular membrane into the neuronal cytosol. Currently, polyclonal immunoglobulins against tetanus neurotoxin obtained from human plasma of hyper-immunized donors are utilized for passive immunotherapy of tetanus; however, these preparations have many disadvantages including high lot-to-lot heterogeneity, possibility of transmitting microbial agents, and the adverse reactions to the other proteins in the plasma. Neutralizing anti-tetanus neurotoxin monoclonal antibodies (MAbs) lack these drawbacks and could be considered as a suitable alternative for passive immunotherapy of tetanus. In this review, we provide an overview of the literature discussing epitope mapping of the published neutralizing MAbs against tetanus toxin.
破伤风是一种危及生命的疾病，其特征为肌肉痉挛。该病由破伤风梭菌产生的神经毒素引起。破伤风神经毒素的活性形式由轻链（片段 A）和重链组成。片段 A 是一种锌金属蛋白酶，可切割神经元可溶性 N-乙基马来酰亚胺敏感的附着受体（SNARE）蛋白，导致抑制性神经递质释放受阻，随后出现全身肌肉痉挛。重链的两个功能域为片段 C，其对于毒素与神经元的细胞结合以及随后的内吞作用至关重要，片段 B 对于片段 A 穿过囊泡膜转运到神经元胞质溶胶也很重要。目前，从高免疫供体的人类血浆中获得的针对破伤风神经毒素的多克隆免疫球蛋白用于破伤风的被动免疫疗法；然而，这些制剂存在许多缺点，包括批次间高度不均一性、传播微生物制剂的可能性以及对血浆中其他蛋白质的不良反应。中和抗破伤风神经毒素单克隆抗体（MAb）缺乏这些缺点，可被视为破伤风被动免疫疗法的合适替代品。在这篇综述中，我们提供了对已发表的中和抗破伤风毒素 MAb 表位作图文献的概述。
