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从黄肥尾蝎中分离和鉴定针对 Ts1 毒素的人抗体片段。

Isolation and characterization of a human antibody fragment specific for Ts1 toxin from Tityus serrulatus scorpion.

机构信息

Department of Molecular Medicine and Bioprocesses, Instituto de Biotecnologia, Universidad Nacional Autónoma de México, Avenida Universidad, 2001, Col. Chamilpa 510-3, Cuernavaca 62210, Mexico.

出版信息

Immunol Lett. 2011 Sep 30;139(1-2):73-9. doi: 10.1016/j.imlet.2011.05.002. Epub 2011 May 19.

Abstract

Scorpion stings are a common event that occurs in tropical and subtropical areas of the world, being a public health problem in certain countries. In most places, medical treatment relays on antivenoms obtained from the sera of hyper-immunized horses, however some efforts are being made to prepare specific antibodies of human origin, using phage display methodology. This communication describes the strategy followed for obtaining a protective human single chain antibody (scFv) capable of partially neutralizing the effect of Ts1, the major toxin isolated from the venom of the Brazilian scorpion Tityus serrulatus. Phage display technique allowed the isolation of scFv 15e from a human library of antibodies, after four rounds of selection against Ts1. This clone codes for 124 amino acids belonging to the family VH6 and 114 amino acids of family VK4. This scFv also recognizes toxins from the scorpions Tityus packyurus and Tityus cambridgei from the Amazonian region. Mice challenged with a LD(50) of Ts1 in the presence of this scFv were substantially resistant to intoxication. ScFv 15e is a leading compound for the development of better anti-scorpion antidotes.

摘要

蝎子蜇伤是世界上热带和亚热带地区常见的事件,在某些国家是一个公共卫生问题。在大多数地方,医疗依赖于从高度免疫的马血清中获得的抗蛇毒血清,然而,人们正在努力使用噬菌体展示技术制备源自人源的特异性抗体。本通讯描述了一种从巴西蝎子 Tityus serrulatus 毒液中分离出的主要毒素 Ts1 中获得部分中和其效应的保护性人源单链抗体 (scFv) 的策略。噬菌体展示技术允许从人类抗体文库中分离出 scFv 15e,经过四轮针对 Ts1 的筛选。该克隆编码 124 个属于 VH6 家族的氨基酸和 114 个属于 VK4 家族的氨基酸。该 scFv 还识别来自亚马逊地区的 Tityus packyurus 和 Tityus cambridgei 蝎子的毒素。在存在这种 scFv 的情况下,用 LD(50) 剂量 Ts1 挑战的小鼠对中毒有很强的抵抗力。ScFv 15e 是开发更好的抗蝎毒解毒剂的先导化合物。

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