In vivo neutralization of coral snake venoms with an oligoclonal nanobody mixture in a murine challenge model

Melisa Benard-Valle, Yessica Wouters, Anne Ljungars, Giang Thi Tuyet Nguyen, Shirin Ahmadi, Tasja Wainani Ebersole, Camilla Holst Dahl, Alid Guadarrama-Martínez, Frederikke Jeppesen, Helena Eriksen, Gibran Rodríguez-Barrera, Kim Boddum, Timothy Patrick Jenkins, Sara Petersen Bjørn, Sanne Schoffelen, Bjørn Gunnar Voldborg, Alejandro Alagón, Andreas Hougaard Laustsen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Oligoclonal mixtures of broadly-neutralizing antibodies can neutralize complex compositions of similar and dissimilar antigens, making them versatile tools for the treatment of e.g., infectious diseases and animal envenomations. However, these biotherapeutics are complicated to develop due to their complex nature. In this work, we describe the application of various strategies for the discovery of cross-neutralizing nanobodies against key toxins in coral snake venoms using phage display technology. We prepare two oligoclonal mixtures of nanobodies and demonstrate their ability to neutralize the lethality induced by two North American coral snake venoms in mice, while individual nanobodies fail to do so. We thus show that an oligoclonal mixture of nanobodies can neutralize the lethality of venoms where the clinical syndrome is caused by more than one toxin family in a murine challenge model. The approaches described may find utility for the development of advanced biotherapeutics against snakebite envenomation and other pathologies where multi-epitope targeting is beneficial.
Original languageEnglish
Article number4310
JournalNature Communications
Volume15
Number of pages13
ISSN2041-1723
DOIs
Publication statusPublished - 2024

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