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http://hdl.handle.net/20.500.12390/2874


Título: Development of Nanobodies Against Hemorrhagic and Myotoxic Components of Bothrops atrox Snake Venom
Autor(es): Calderon, Henri Bailon 
Coronel, Veronica Olga Yaniro 
Rey, Omar Alberto Caceres 
Alave, Elizabeth Gaby Colque 
Duran, Walter Jhon Leiva 
Rojas, Carlos Padilla 
Arevalo, Harrison Montejo 
Neyra, David Garcia 
Perez, Marco Galarza 
Bonilla, Cesar 
Tintaya, Benigno 
Ricciardi, Giulia 
Smiejkowska, Natalia 
Romao, Ema 
Vincke, Cecile 
Levano, Juan 
Celys, Mary 
Lomonte, Bruno 
Muyldermans, Serge 
Resumen: Snake envenoming is a globally neglected public health problem. Antivenoms produced using animal hyperimmune plasma remain the standard therapy for snakebites. Although effective against systemic effects, conventional antivenoms have limited efficacy against local tissue damage. In addition, potential hypersensitivity reactions, high costs for animal maintenance, and difficulties in obtaining batch-to-batch homogeneity are some of the factors that have motivated the search for innovative and improved therapeutic products against such envenoming. In this study, we have developed a set of nanobodies (recombinant single-domain antigen-binding fragments from camelid heavy chain-only antibodies) against Bothrops atrox snake venom hemorrhagic and myotoxic components. An immune library was constructed after immunizing a Lama glama with whole venom of B. atrox, from which nanobodies were selected by phage display using partially purified hemorrhagic and myotoxic proteins. Biopanning selections retrieved 18 and eight different nanobodies against the hemorrhagic and the myotoxic proteins, respectively. In vivo assays in mice showed that five nanobodies inhibited the hemorrhagic activity of the proteins; three neutralized the hemorrhagic activity of whole B. atrox venom, while four nanobodies inhibited the myotoxic protein. A mixture of the anti-hemorrhagic and anti-myotoxic nanobodies neutralized the local tissue hemorrhage and myonecrosis induced by the whole venom, although the nanobody mixture failed to prevent the venom lethality. Nevertheless, our results demonstrate the efficacy and usefulness of these nanobodies to neutralize important pathologies of the venom, highlighting their potential as innovative therapeutic agents against envenoming by B. atrox, a viperid species causing many casualties in South America.
Tema: Immunology;Immunology and Allergy
Editorial: Frontiers Media SA
Fecha de publicación: 2020
Publicado en: FRONTIERS IN IMMUNOLOGY 
Financiamiento: CONV-000188-2015-FONDECYT-DE 
Tipo de publicación: info:eu-repo/semantics/article
Identificador Handle: http://hdl.handle.net/20.500.12390/2874
DOI: 10.3389/fimmu.2020.00655
Nivel de acceso: info:eu-repo/semantics/closedAccess
Colección:6.1 Proyectos de investigación científica

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