Laboratory of Synthetic Biology and Biomimetics, Insituto de Ciências Biológicas, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Colégio Técnico (Coltec), Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Vaccine. 2018 Nov 19;36(48):7324-7330. doi: 10.1016/j.vaccine.2018.10.035. Epub 2018 Oct 21.
Accidents with venomous animals pose a health issue in Brazil, and those involving brown spiders (Loxosceles sp.) figure between the most frequent ones. The accidental envenomation by brown spiders causes a strong local dermonecrotic effect, which can be followed by systemic manifestations that in some cases lead to death. The production of antivenoms for the treatments of such accidents relies on a variety of animal experiments, from the spider venom extraction to the production of antivenom in horses. In the present work, there is an attempt to reduce and optimize animal experiments with the construction and production of a chimeric protein, named Lil, containing immunodominant epitopes previously mapped from the main proteins of the Loxosceles venom, the Sphingomyelinases D. The Lil protein contains epitopes from Sphinomyelinases D of the three-main species found in Brazil and this chimeric protein was found capable of inducing antibodies with the potential to partially neutralize the toxic effects of Loxosceles intermedia venom in an animal model. Therefore, in order to reduce spider usage and to improve the lifespan of the horses used for immunization we suggest the Lil protein as a potential candidate to replace the venom usage in the antivenom production protocols.
巴西存在因接触毒液动物而产生的健康问题，其中涉及棕色蜘蛛（Loxosceles sp.）的事故较为常见。棕色蜘蛛的意外螫伤会导致强烈的局部皮肤坏死效应，并可能伴有全身性表现，在某些情况下会导致死亡。针对此类事故的抗蛇毒血清的生产依赖于各种动物实验，从蜘蛛毒液提取到马抗蛇毒血清的生产。在本工作中，我们尝试通过构建和生产一种嵌合蛋白 Lil 来减少和优化动物实验，该蛋白包含先前从 Loxosceles 毒液的主要蛋白（鞘磷脂酶 D）中映射出的免疫显性表位。Lil 蛋白包含来自巴西三种主要蜘蛛的 Sphingomyelinases D 的表位，该嵌合蛋白能够诱导产生潜在中和 Loxosceles intermedia 毒液毒性作用的抗体，在动物模型中具有中和作用。因此，为了减少蜘蛛的使用并延长用于免疫的马的寿命，我们建议使用 Lil 蛋白作为替代毒液的潜在候选物，用于抗蛇毒血清生产方案。
