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

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 option<sup>1</sup>. 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 species<sup>2</sup>. 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 venoms<sup>3</sup>. 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.

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Publication Details

Journal
Nature
Published
2025-10-29
DOI
https://doi.org/10.1038/s41586-025-09661-0
Citations
12
Primary Topic
Venomous Animal Envenomation and Studies
Type
article
Field-Weighted Citation Impact
21.81
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article

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

Amy E. Marriott, Alid Guadarrama-Martínez, Tom G. T. Jansen, Suthimon Thumtecho et al.
12 citations
Nature
Venomous Animal Envenomation and Studies
21.81
article

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

Amy E. Marriott, Alid Guadarrama-Martínez, Tom G. T. Jansen, Suthimon Thumtecho, Stefanie K. Menzies, Melisa Bénard-Valle, Édgar Neri-Castro, Tasja Wainani Ebersole, Yessica Wouters, Monica L. Fernández‐Quintero, Jens Preben Morth, Anne Ljungars, Iara Aimê Cardoso, Carol O’Brien, Andreas H. Laustsen, Stephen P. Mackessy, Timothy P. Jenkins, Kim Boddum, Shirin Ahmadi, Konstantinos Kalogeropoulos, Edouard Crittenden, Rebecca J. Edge, Giang Thi Tuyet Nguyen, Esperanza Rivera‐de‐Torre, Nicholas R. Casewell, Stuart Ainsworth, Nick J. Burlet, Alejandro Alagón, Camilla Holst Dahl, Samuel R Kerwin, Emily U. Glegg-Sørensen, Evangelia Manousaki
article en
12 citations

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 option<sup>1</sup>. 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 species<sup>2</sup>. 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 venoms<sup>3</sup>. 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.

NatureVol. 647(8090)
Scripps Research Institute (US), Thai Red Cross Society (TH), University of Liverpool (GB), Chulalongkorn University (TH), Liverpool School of Tropical Medicine (GB), King Chulalongkorn Memorial Hospital (TH), University of Bristol (GB), Lancaster University (GB), University of Northern Colorado (US), Universidad Nacional Autónoma de México (MX), Technical University of Denmark (DK)
Openalex Percentile: Top 0%
Venomous Animal Envenomation and Studies
21.81
DOIOpen Access PDFOpenAlex
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