Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México - UNAM, Apartado Postal 510-3, Cuernavaca Morelos, 61500, Mexico.
The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, M5S3E1, Canada.
Nat Commun. 2019 Aug 13;10(1):3642. doi: 10.1038/s41467-019-11639-2.
Antivenoms are fundamental in the therapy for snakebites. In elapid venoms, there are toxins, e.g. short-chain α-neurotoxins, which are quite abundant, highly toxic, and consequently play a major role in envenomation processes. The core problem is that such α-neurotoxins are weakly immunogenic, and many current elapid antivenoms show low reactivity towards them. We have previously developed a recombinant consensus short-chain α-neurotoxin (ScNtx) based on sequences from the most lethal elapid venoms from America, Africa, Asia, and Oceania. Here we report that an antivenom generated by immunizing horses with ScNtx can successfully neutralize the lethality of pure recombinant and native short-chain α-neurotoxins, as well as whole neurotoxic elapid venoms from diverse genera such as Micrurus, Dendroaspis, Naja, Walterinnesia, Ophiophagus and Hydrophis. These results provide a proof-of-principle for using recombinant proteins with rationally designed consensus sequences as universal immunogens for developing next-generation antivenoms with higher effectiveness and broader neutralizing capacity.
抗蛇毒血清是蛇伤治疗的基础。在眼镜蛇毒液中，存在着大量的毒素，如短链α-神经毒素，它们具有高度的毒性，因此在蛇伤过程中起着主要作用。核心问题是，这些α-神经毒素的免疫原性较弱，许多现有的眼镜蛇抗蛇毒血清对其反应性较低。我们之前基于来自美洲、非洲、亚洲和大洋洲最致命的眼镜蛇毒液的序列，开发了一种重组的短链α-神经毒素（ScNtx）的共识序列。在这里，我们报告了一种通过用 ScNtx 免疫马而产生的抗蛇毒血清，能够成功中和纯重组和天然短链α-神经毒素以及来自各种属的全神经毒性眼镜蛇毒液的致死性，如 Micrurus、Dendroaspis、Naja、Walterinnesia、Ophiophagus 和 Hydrophis。这些结果为使用具有合理设计的共识序列的重组蛋白作为通用免疫原，开发具有更高有效性和更广泛中和能力的下一代抗蛇毒血清提供了原理上的证明。
