Department of Biotechnology and Biomedicine, Technical University of Denmark, DK-2800, Kongens Lyngby, Denmark.
Sophion Bioscience, DK-2750, Ballerup, Denmark.
Nat Commun. 2023 Feb 8;14(1):682. doi: 10.1038/s41467-023-36393-4.
Snakebite envenoming continues to claim many lives across the globe, necessitating the development of improved therapies. To this end, broadly-neutralizing human monoclonal antibodies may possess advantages over current plasma-derived antivenoms by offering superior safety and high neutralization capacity. Here, we report the establishment of a pipeline based on phage display technology for the discovery and optimization of high affinity broadly-neutralizing human monoclonal antibodies. This approach yielded a recombinant human antibody with superior broadly-neutralizing capacities in vitro and in vivo against different long-chain α-neurotoxins from elapid snakes. This antibody prevents lethality induced by Naja kaouthia whole venom at an unprecedented low molar ratio of one antibody per toxin and prolongs the survival of mice injected with Dendroaspis polylepis or Ophiophagus hannah whole venoms.
蛇伤中毒仍然在全球范围内夺走许多生命，因此需要开发改进的治疗方法。为此，广泛中和的人源单克隆抗体可能比目前的血浆来源抗蛇毒血清具有优势，因为它们具有更高的安全性和更高的中和能力。在这里，我们报告了一个基于噬菌体展示技术的发现和优化高亲和力广泛中和人源单克隆抗体的管道的建立。这种方法产生了一种重组人抗体，它对来自眼镜蛇科的不同长链α-神经毒素具有优越的体外和体内广泛中和能力。该抗体以前所未有的每毒素一个抗体的低摩尔比预防 Naja kaouthia 全毒液引起的致死性，并延长注射 Dendroaspis polylepis 或 Ophiophagus hannah 全毒液的小鼠的存活时间。
