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Dendritic Cell-Mediated Cross-Priming by a Bispecific Neutralizing Antibody Boosts Cytotoxic T Cell Responses and Protects Mice against SARS-CoV-2.
dc.contributor.author | Lázaro-Gorines, Rodrigo | |
dc.contributor.author | Pérez, Patricia | |
dc.contributor.author | Heras-Murillo, Ignacio | |
dc.contributor.author | Rubio Pérez, Laura | |
dc.contributor.author | Álvarez-Vallina, Luis | |
dc.date.accessioned | 2024-02-14T10:59:46Z | |
dc.date.available | 2024-02-14T10:59:46Z | |
dc.date.issued | 2023 | |
dc.identifier.issn | 2198-3844 | spa |
dc.identifier.uri | https://hdl.handle.net/10641/3989 | |
dc.description.abstract | Administration of neutralizing antibodies (nAbs) has proved to be effective by providing immediate protection against SARS-CoV-2. However, dual strategies combining virus neutralization and immune response stimulation to enhance specific cytotoxic T cell responses, such as dendritic cell (DC) cross-priming, represent a promising field but have not yet been explored. Here, a broadly nAb, TNT, are first generated by grafting an anti-RBD biparatopic tandem nanobody onto a trimerbody scaffold. Cryo-EM data show that the TNT structure allows simultaneous binding to all six RBD epitopes, demonstrating a high-avidity neutralizing interaction. Then, by C-terminal fusion of an anti-DNGR-1 scFv to TNT, the bispecific trimerbody TNTDNGR-1 is generated to target neutralized virions to type 1 conventional DCs (cDC1s) and promote T cell cross-priming. Therapeutic administration of TNTDNGR-1, but not TNT, protects K18-hACE2 mice from a lethal SARS-CoV-2 infection, boosting virus-specific humoral responses and CD8+ T cell responses. These results further strengthen the central role of interactions with immune cells in the virus-neutralizing antibody activity and demonstrate the therapeutic potential of the Fc-free strategy that can be used advantageously to provide both immediate and long-term protection against SARS-CoV-2 and other viral infections. | spa |
dc.language.iso | eng | spa |
dc.publisher | Advanced Science | spa |
dc.rights | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.title | Dendritic Cell-Mediated Cross-Priming by a Bispecific Neutralizing Antibody Boosts Cytotoxic T Cell Responses and Protects Mice against SARS-CoV-2. | spa |
dc.type | journal article | spa |
dc.type.hasVersion | AM | spa |
dc.rights.accessRights | open access | spa |
dc.description.extent | 2527 KB | spa |
dc.identifier.doi | 10.1002/advs.202304818 | spa |
dc.relation.publisherversion | https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202304818 | spa |
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