丹麦技术大学Andreas H. Laustsen研究小组宣布他们探明了基于纳米体的重组抗蛇毒血清用于眼镜蛇、曼巴和白鼬咬伤。该研究于2025年10月29日发表于国际一流学术期刊《自然》杂志上。

为了解决这一挑战，研究小组用18种不同蛇的毒液对羊驼和美洲驼进行了免疫，包括曼巴蛇、眼镜蛇和圆齿蛇，构建了噬菌体展示库，并鉴定了高亲和力的广泛中和纳米体。小组将其中的8个纳米体组合成一种确定的寡克隆混合物，从而产生一种实验性的多价重组抗蛇毒血清，该抗蛇毒血清能够中和7个毒素家族或亚家族。该抗蛇毒血清有效地预防了17种非洲蛇的体内毒素致死性，并显著减少了所有测试的细胞毒性毒液的毒素致皮肤坏死。重组抗蛇毒血清比目前主题的血浆衍生抗蛇毒血清表现更好，因此显示出相当大的希望，可以全面保护整个大陆免受所有医学上相关的非洲蛇咬伤。

据介绍，在撒哈拉以南非洲地区，毒蛇咬伤每年夺去许多人的生命，并给受害者造成严重伤害，其中许多人依赖从动物血浆中提取的抗蛇毒血清作为唯一的治疗选择。传统的抗蛇毒血清价格昂贵，可能引起不良的免疫反应，对局部组织损伤的疗效有限，而且通常对所有医学上相关的蛇类无效。他们迫切需要在蛇咬伤治疗方面进行创新。然而，开发广谱治疗是极具挑战性的，因为毒液蛇种类繁多，而且它们的毒液成分复杂多变。

附：英文原文

Title: Nanobody-based recombinant antivenom for cobra, mamba and rinkhals bites

Author: Ahmadi, Shirin, Burlet, Nick J., Benard-Valle, Melisa, Guadarrama-Martnez, Alid, Kerwin, Samuel, Cardoso, Iara A., Marriott, Amy E., Edge, Rebecca J., Crittenden, Edouard, Neri-Castro, Edgar, Fernandez-Quintero, Monica L., Nguyen, Giang T. T., OBrien, Carol, Wouters, Yessica, Kalogeropoulos, Konstantinos, Thumtecho, Suthimon, Ebersole, Tasja Wainani, Dahl, Camilla Holst, Glegg-Srensen, Emily U., Jansen, Tom, Boddum, Kim, Manousaki, Evangelia, Rivera-de-Torre, Esperanza, Ward, Andrew B., Morth, J. Preben, Alagn, Alejandro, Mackessy, Stephen P., Ainsworth, Stuart, Menzies, Stefanie K., Casewell, Nicholas R., Jenkins, Timothy P., Ljungars, Anne, Laustsen, Andreas H.

Issue&Volume: 2025-10-29

Abstract: Each year, snakebite envenoming claims thousands of lives and causes severe injury to victims across sub-Saharan Africa, many of whom depend on antivenoms derived from animal plasma as their sole treatment option1. Traditional antivenoms are expensive, can cause adverse immunological reactions, offer limited efficacy against local tissue damage and are often ineffective against all medically relevant snake species2. There is thus an urgent unmet medical need for innovation in snakebite envenoming therapy. However, developing broad-spectrum treatments is highly challenging owing to the vast diversity of venomous snakes and the complex and variable composition of their venoms3. Here we addressed this challenge by immunizing an alpaca and a llama with the venoms of 18 different snakes, including mambas, cobras and a rinkhals, constructing phage display libraries, and identifying high-affinity broadly neutralizing nanobodies. We combined eight of these nanobodies into a defined oligoclonal mixture, resulting in an experimental polyvalent recombinant antivenom that was capable of neutralizing seven toxin families or subfamilies. This antivenom effectively prevented venom-induced lethality in vivo across 17 African elapid snake species and markedly reduced venom-induced dermonecrosis for all tested cytotoxic venoms. The recombinant antivenom performed better than a currently used plasma-derived antivenom and therefore shows considerable promise for comprehensive, continent-wide protection against snakebites by all medically relevant African elapids.

DOI: 10.1038/s41586-025-09661-0

Source: https://www.nature.com/articles/s41586-025-09661-0