Karim-Silva Sabrina, Moura Juliana de, Noiray Magali, Minozzo Joao Carlos, Aubrey Nicolas, Alvarenga Larissa M, Billiald Philippe
Universidade Federal do Parana, Departamento de Patologia Basica, Laboratorio de Imunoquimica, Curitiba, PR, Brazil.
University Paris-Sud, School of Pharmacy, UMS IPSIT, 5 rue J.-B. Clément, 92296 Châtenay-Malabry, France.
Immunol Lett. 2016 Aug;176:90-6. doi: 10.1016/j.imlet.2016.05.019. Epub 2016 Jun 7.
Loxosceles spider bites often lead to serious envenomings and no definite therapy has yet been established. In such a context, it is of interest to consider an antibody-based targeted therapy. We have previously prepared a murine monoclonal IgG (LiMab7) that binds to 32-35kDa components of Loxosceles intermedia venom and neutralizes the dermonecrotic activity of the venom. Here, we re-engineered LiMab7 into a recombinant diabody. The protein was produced in bacteria and then it was functionally characterized. It proved to be efficient at neutralizing sphingomyelinase and hemolytic activities of the crude venom despite the slightly altered binding kinetic constants and the limited stability of the dimeric configuration. This is the first report of a specific recombinant antibody for a next-generation of Loxosceles antivenoms.
巴西游走蛛叮咬常常导致严重的中毒反应，目前尚未确立明确的治疗方法。在此背景下，考虑基于抗体的靶向治疗很有意义。我们之前制备了一种鼠单克隆IgG（LiMab7），它能结合巴西中间游走蛛毒液的32 - 35 kDa成分，并中和毒液的皮肤坏死活性。在此，我们将LiMab7改造为重组双抗体。该蛋白在细菌中产生，然后对其进行功能表征。尽管结合动力学常数略有改变且二聚体构型稳定性有限，但它在中和粗毒液的鞘磷脂酶和溶血活性方面证明是有效的。这是关于新一代巴西游走蛛抗蛇毒血清特异性重组抗体的首次报道。
