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The venom of the scorpion Centruroides limpidus, which causes the highest number of stings in Mexico, is neutralized by two recombinant antibody fragments
Molecular Immunology ( IF 3.2 ) Pub Date : 2021-07-20 , DOI: 10.1016/j.molimm.2021.07.010
Guillermo Fernández-Taboada 1 , Lidia Riaño-Umbarila 2 , Alejandro Olvera-Rodríguez 1 , Ilse Viridiana Gómez-Ramírez 1 , Luis Fernando Losoya-Uribe 1 , Baltazar Becerril 1
Affiliation  

Phage display and directed evolution have made it possible to generate recombinant antibodies in the format of single chain variable fragments (scFvs) capable of neutralizing different toxins and venoms of Mexican scorpions. Despite having managed to neutralize a significant number of venoms, some others have not yet been completely neutralized, due to the diversity of the toxic components present in them. An example is the venom of the scorpion Centruroides limpidus, which contains three toxins of medical importance, called Cll1, Cll2 and Cl13. The first two are neutralized by scFv 10FG2, while Cl13, due to its sequence divergence, was not even recognized. For this reason, the aim of the present work was the generation of a new scFv capable of neutralizing Cl13 toxin and thereby helping to neutralize the whole venom of this scorpion. By hybridoma technology, a monoclonal antibody (mAb B7) was generated, which was able to recognize and partially neutralize Cl13 toxin. From mAb B7, its scFv format was obtained, named scFv B7 and subjected to three cycles of directed evolution. At the end of these processes, scFv 11F which neutralized Cl13 toxin was obtained. This scFv, administered in conjunction with scFv 10FG2, allowed to fully neutralize the whole venom of Centruroides limpidus scorpion.



中文翻译:

在墨西哥造成最多蜇伤的蝎子 Centruroides limpidus 的毒液被两个重组抗体片段中和

噬菌体展示和定向进化使产生单链可变片段 (scFvs) 形式的重组抗体成为可能,能够中和墨西哥蝎子的不同毒素和毒液。尽管已经设法中和了大量毒液,但由于其中存在的有毒成分的多样性,其他一些毒液尚未完全中和。一个例子是蝎子Centruroides limpidus的毒液,其中包含三种具有医学重要性的毒素,称为 Cll1、Cll2 和 Cl13。前两个被 scFv 10FG2 中和,而 Cl13 由于其序列差异,甚至未被识别。出于这个原因,目前工作的目的是产生一种能够中和 Cl13 毒素的新 scFv,从而帮助中和这只蝎子的整个毒液。通过杂交瘤技术,产生了单克隆抗体(mAb B7),能够识别并部分中和Cl13毒素。从 mAb B7 中获得了它的 scFv 形式,命名为 scFv B7 并经过三个循环的定向进化。在这些过程结束时,获得了中和 Cl13 毒素的 scFv 11F。该 scFv 与 scFv 10FG2 联合给药,可以完全中和Centruroides limpidus的整个毒液 蝎。

更新日期:2021-07-21
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