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 and Andreas Hougaard Laustsen ()
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Melisa Benard-Valle: Technical University of Denmark
Yessica Wouters: Technical University of Denmark
Anne Ljungars: Technical University of Denmark
Giang Thi Tuyet Nguyen: Technical University of Denmark
Shirin Ahmadi: Technical University of Denmark
Tasja Wainani Ebersole: Technical University of Denmark
Camilla Holst Dahl: Technical University of Denmark
Alid Guadarrama-Martínez: Universidad Nacional Autónoma de México
Frederikke Jeppesen: Technical University of Denmark
Helena Eriksen: Technical University of Denmark
Gibran Rodríguez-Barrera: Universidad Nacional Autónoma de México
Kim Boddum: Sophion Bioscience
Timothy Patrick Jenkins: Technical University of Denmark
Sara Petersen Bjørn: Technical University of Denmark
Sanne Schoffelen: Technical University of Denmark
Bjørn Gunnar Voldborg: Technical University of Denmark
Alejandro Alagón: Universidad Nacional Autónoma de México
Andreas Hougaard Laustsen: Technical University of Denmark

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-48539-z

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