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

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Ahmadi, Shirin, Burlet, Nick J ORCID: 0009-0002-5099-3971, Benard-Valle, Melisa ORCID: 0000-0002-0042-6592, Guadarrama-Martínez, Alid ORCID: 0009-0007-6378-0859, Kerwin, Samuel, Cardoso, Iara A ORCID: 0000-0002-0288-4706, Marriott, Amy E, Edge, Rebecca J ORCID: 0000-0001-8574-3724, Crittenden, Edouard ORCID: 0000-0003-1676-5457, Neri-Castro, Edgar et al (show 23 more authors) , Fernandez-Quintero, Monica L, Nguyen, Giang TT ORCID: 0000-0002-3536-9903, O'Brien, Carol, Wouters, Yessica, Kalogeropoulos, Konstantinos ORCID: 0000-0003-3907-9281, Thumtecho, Suthimon ORCID: 0000-0002-8853-6568, Ebersole, Tasja Wainani, Dahl, Camilla Holst, Glegg-Sørensen, Emily U, Jansen, Tom ORCID: 0000-0001-8006-8627, Boddum, Kim ORCID: 0000-0002-1588-9055, Manousaki, Evangelia, Rivera-de-Torre, Esperanza ORCID: 0000-0002-0272-6150, Ward, Andrew B ORCID: 0000-0001-7153-3769, Morth, J Preben ORCID: 0000-0003-4077-0192, Alagón, Alejandro ORCID: 0000-0003-1721-3726, Mackessy, Stephen P ORCID: 0000-0003-4515-2545, Ainsworth, Stuart ORCID: 0000-0002-0199-6482, Menzies, Stefanie K ORCID: 0000-0002-9273-9296, Casewell, Nicholas R ORCID: 0000-0002-8035-4719, Jenkins, Timothy P ORCID: 0000-0003-2979-5663, Ljungars, Anne ORCID: 0000-0002-2158-0601 and Laustsen, Andreas H ORCID: 0000-0001-6918-5574 (2025) Nanobody-based recombinant antivenom for cobra, mamba and rinkhals bites. Nature, 647 (8090). pp. 716-725. ISSN 0028-0836, 1476-4687

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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.

Item Type:	Article
Uncontrolled Keywords:	Animals, Antivenins, Snake Bites, Single-Domain Antibodies, Camelids, New World, Antibodies, Neutralizing, Recombinant Proteins, Female, Male, Elapid Venoms, Humans, Neutralization Tests, Camelidae, Peptide Library, Mice
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Infection, Vet & Ecological Sciences Faculty of Health & Life Sciences > Inst. Infection, Vet & Ecological Sciences > Infection Biology & Microbiomes Faculty of Health & Life Sciences > Inst. Infection, Vet & Ecological Sciences > Inst. Infection, Vet & Ecological Sciences (T&R Staff) Faculty of Health & Life Sciences > Tech, Infrastructure & Env Directorate Faculty of Health & Life Sciences > Tech, Infrastructure & Env Directorate > Liverpool Shared Research Facilities
Depositing User:	Symplectic Admin
Date Deposited:	31 Oct 2025 10:45
Last Modified:	27 Nov 2025 13:36
DOI:	10.1038/s41586-025-09661-0
Open Access URL:	https://www.nature.com/articles/s41586-025-09661-0
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3195121
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