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

• Published in: Nature communications Vol. 15; no. 1; p. 4310
• Main Authors: Benard-Valle, Melisa, Wouters, Yessica, Ljungars, Anne, Nguyen, Giang Thi Tuyet, Ahmadi, Shirin, Ebersole, Tasja Wainani, Dahl, Camilla Holst, Guadarrama-Martínez, Alid, Jeppesen, Frederikke, Eriksen, Helena, Rodríguez-Barrera, Gibran, Boddum, Kim, Jenkins, Timothy Patrick, Bjørn, Sara Petersen, Schoffelen, Sanne, Voldborg, Bjørn Gunnar, Alagón, Alejandro, Laustsen, Andreas Hougaard
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.05.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 49/1; 49/23; 631/250/2520; 631/61; 64/60; 692/308/1426; 692/308/153; 82/1; 82/16; 82/80; 82/83; 9/74; Animal diseases; Animal models; Animals; Antibodies; Antibodies, Neutralizing - immunology; Antigens; Antivenins - immunology; Cell Surface Display Techniques; Coral Snakes - immunology; Disease Models, Animal; Display devices; Elapid Venoms - immunology; Epitopes; Epitopes - immunology; Female; Health services; Humanities and Social Sciences; Infectious diseases; Lethality; Mice; Mice, Inbred BALB C; Mixtures; multidisciplinary; Nanobodies; Neutralization; Neutralizing; Phage display; Predation; Science; Science (multidisciplinary); Single-Domain Antibodies - immunology; Snake bites; Snake Bites - immunology; Snake Bites - therapy; Snakes; Toxins; Venom; Venom toxins
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-48539-z

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. Oligoclonal mixtures of neutralising antibodies can target multiple antigen components and represent a potential therapeutic solution for the treatment of envenomation. Here, the authors generate mixtures of nanobodies against coral snake venom toxins and demonstrate they can prevent lethality of coral snake venoms in pre-clinical animal models.