Neutralization of Lethal Potency of Tetanus Toxin using Phage Display Produced scFv Antibody

E. Khalili, E. Abbasi, M. Aminian
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Abstract

Background and Aim: Phage display technology provides a new approach for making human antibody fragments that could be applicable in passive immune therapy. We applied the use of this technology to make human single-chain variable fragments (scFvs) specific for tetanus toxin. Tetanus toxin is a neurotoxin constituted by the association of two subunits, mediates its lethal action by blocking neuromuscular vesicle docking. Methods: We previously found that six Human scFv clones inhibit toxin binding to ganglioside GT1b. This is the final report of human tetanus scFvs (scFv 8 and scFv 13) isolated from an immunized library of more than 106 scFv clones with in vivo neutralizing activity. Results: Only scFv 13 can reduce the in vivo toxicity induced by tetanus toxin. Also, scFv 8 has a weak capability of reducing the in vivo toxicity of the toxin. Conclusion: These selected ScFvs can be considered as a possible option to substitute the human tetanus immunoglobulin (HTIG) which is extensively current immunotherapy for tetanus patients. Taken together, our results suggest that the use of human tetanus scFvs may lead to a less aggressive passive immune therapy against tetanus. *Corresponding Author: Mahdi Aminian; Email: amminian@tums.ac.ir Please cite this article as: Khalili E, Abbasi E, Aminian M. Neutralization of Lethal Potency of Tetanus Toxin using Phage Display Produced ScFv Antibody.Arch Med Lab Sci. 2021;7:(e3). https://doi.org/10.22037/amls.v7.33786
利用噬菌体展示产生的单链抗体中和破伤风毒素的致死效力
背景与目的:噬菌体展示技术为制备可用于被动免疫治疗的人抗体片段提供了新的途径。我们应用该技术制备了破伤风毒素特异性的人单链可变片段(scFvs)。破伤风毒素是一种由两个亚基结合而成的神经毒素,通过阻断神经肌肉囊泡对接来介导其致死性作用。方法:我们先前发现6个人类scFv克隆抑制毒素与神经节苷脂GT1b的结合。这是从超过106个具有体内中和活性的人破伤风单链病毒(scFv 8和scFv 13)免疫文库中分离得到的最终报告。结果:仅scfv13能降低破伤风毒素的体内毒性。同时,scfv8降低毒素体内毒性的能力较弱。结论:经筛选的ScFvs可作为替代目前广泛用于破伤风患者免疫治疗的人破伤风免疫球蛋白(HTIG)的可能选择。综上所述,我们的研究结果表明,使用人破伤风scFvs可能导致对破伤风的被动免疫治疗不那么积极。*通讯作者:Mahdi Aminian;电子邮件:amminian@tums.ac.ir请引用这篇文章:Khalili E, Abbasi E, Aminian M.利用噬菌体展示产生的ScFv抗体中和破伤风毒素致死效力。中华医学杂志,2021;7:(3)。https://doi.org/10.22037/amls.v7.33786
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