TBI, Université de Toulouse, CNRS, INRAE, INSA, Toulouse, France.
Laboratoire Des Venins Et Molécules Thérapeutiques, Institut Pasteur de Tunis, Université de Tunis El Manar, 13 Place Pasteur BP74, 1002, Tunis, Tunisia.
Appl Microbiol Biotechnol. 2023 Jul;107(13):4133-4152. doi: 10.1007/s00253-023-12578-1. Epub 2023 May 18.
Scorpion envenomation is a serious health problem in tropical and subtropical zones. The access to scorpion antivenom is sometimes limited in availability and specificity. The classical production process is cumbersome, from the hyper-immunization of the horses to the IgG digestion and purification of the F(ab)' antibody fragments. The production of recombinant antibody fragments in Escherichia coli is a popular trend due to the ability of this microbial host to produce correctly folded proteins. Small recombinant antibody fragments, such as single-chain variable fragments (scFv) and nanobodies (VH), have been constructed to recognize and neutralize the neurotoxins responsible for the envenomation symptoms in humans. They are the focus of interest of the most recent studies and are proposed as potentially new generation of pharmaceuticals for their use in immunotherapy against scorpion stings of the Buthidae family. This literature review comprises the current status on the scorpion antivenom market and the analyses of cross-reactivity of commercial scorpion anti-serum against non-specific scorpion venoms. Recent studies on the production of new recombinant scFv and nanobodies will be presented, with a focus on the Androctonus and Centruroides scorpion species. Protein engineering-based technology could be the key to obtaining the next generation of therapeutics capable of neutralizing and cross-reacting against several types of scorpion venoms. KEY POINTS: • Commercial antivenoms consist of predominantly purified equine F(ab)'fragments. • Nanobody-based antivenom can neutralize Androctonus venoms and have a low immunogenicity. • Affinity maturation and directed evolution are used to obtain potent scFv families against Centruroides scorpions.
蝎螫伤是热带和亚热带地区严重的健康问题。蝎毒抗血清的获取有时在供应和特异性方面受到限制。经典的生产过程繁琐，从对马的超免疫化到 IgG 的消化和 F(ab)’抗体片段的纯化。由于微生物宿主能够生产正确折叠的蛋白质，因此在大肠杆菌中生产重组抗体片段成为一种流行趋势。构建了小的重组抗体片段，如单链可变片段(scFv)和纳米抗体(VH)，以识别和中和导致人类螫伤症状的神经毒素。它们是最近研究的关注焦点，并被提议作为新一代药物，用于对抗 Buthidae 家族的蝎螫免疫治疗。本文综述了蝎毒抗血清市场的现状，以及对商业蝎毒抗血清对非特异性蝎毒交叉反应性的分析。将介绍新的重组 scFv 和纳米抗体生产的最新研究，重点是 Androctonus 和 Centruroides 蝎种。基于蛋白质工程的技术可能是获得能够中和和交叉反应几种类型蝎毒的下一代治疗药物的关键。关键点：• 商业抗血清主要由纯化的马 F(ab)’片段组成。• 基于纳米抗体的抗血清可以中和 Androctonus 毒液，且免疫原性低。• 亲和力成熟和定向进化用于获得针对 Centruroides 蝎子的有效 scFv 家族。
