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Development of nanobodies against hemorrhagic and myotoxic components of Bothrops atrox snake venom

dc.creatorBailon Calderon, Henri
dc.creatorYaniro Coronel, Verónica Olga
dc.creatorCáceres Rey, Omar Alberto
dc.creatorColque Alave, Elizabeth Gaby
dc.creatorLeiva Duran, Walter Jhon
dc.creatorPadilla Rojas, Carlos
dc.creatorMontejo Arevalo, Harrison
dc.creatorGarcía Neyra, David
dc.creatorGalarza Pérez, Marco
dc.creatorBonilla, César
dc.creatorTintaya, Benigno
dc.creatorRicciardi, Giulia
dc.creatorSmiejkowska, Natalia
dc.creatorRomão, Ema
dc.creatorVincke, Cécile
dc.creatorLévano, Juan
dc.creatorCelys, Mary
dc.creatorLomonte, Bruno
dc.creatorMuyldermans, Serge
dc.date.accessioned2021-03-09T15:01:58Z
dc.date.available2021-03-09T15:01:58Z
dc.date.issued2020
dc.description.abstractSnake 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.es_ES
dc.description.procedenceUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)es_ES
dc.description.sponsorshipNational Council of Science and Technology/[188-2015-FONDECYT]/CONCYTEC-FONDECYT/Perúes_ES
dc.identifier.citationhttps://www.frontiersin.org/articles/10.3389/fimmu.2020.00655/full
dc.identifier.doihttps://doi.org/10.3389/fimmu.2020.00655
dc.identifier.urihttps://hdl.handle.net/10669/82988
dc.language.isoenges_ES
dc.rightsacceso abierto
dc.sourceFrontiers in Immunology (2020) 11, 655es_ES
dc.subjectnanobodieses_ES
dc.subjectmyotoxines_ES
dc.subjecthemorrhagees_ES
dc.subjectBothropses_ES
dc.subjectsnake venomes_ES
dc.titleDevelopment of nanobodies against hemorrhagic and myotoxic components of Bothrops atrox snake venomes_ES
dc.typeartículo original

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