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dc.contributor.author | Hsieh, Ching-Lin | |
dc.contributor.author | Rush, Scott A | |
dc.contributor.author | Palomo-Sanz, Concepcion | |
dc.contributor.author | Chou, Chia-Wei | |
dc.contributor.author | Pickens, Whitney | |
dc.contributor.author | Mas-Lloret, Vicente | |
dc.contributor.author | McLellan, Jason S | |
dc.date.accessioned | 2022-05-24T06:51:58Z | |
dc.date.available | 2022-05-24T06:51:58Z | |
dc.date.issued | 2022-03-14 | |
dc.identifier.citation | Nat Commun. 2022 Mar 14;13(1):1299. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/14467 | |
dc.description.abstract | The human metapneumovirus (hMPV) fusion (F) protein is essential for viral entry and is a key target of neutralizing antibodies and vaccine development. The prefusion conformation is thought to be the optimal vaccine antigen, but previously described prefusion F proteins expressed poorly and were not well stabilized. Here, we use structures of hMPV F to guide the design of 42 variants containing stabilizing substitutions. Through combinatorial addition of disulfide bonds, cavity-filling substitutions, and improved electrostatic interactions, we describe a prefusion-stabilized F protein (DS-CavEs2) that expresses at 15 mg/L and has a melting temperature of 71.9 °C. Crystal structures of two prefusion-stabilized hMPV F variants reveal that antigenic surfaces are largely unperturbed. Importantly, immunization of mice with DS-CavEs2 elicits significantly higher neutralizing antibody titers against hMPV A1 and B1 viruses than postfusion F. The improved properties of DS-CavEs2 will advance the development of hMPV vaccines and the isolation of therapeutic antibodies. | es_ES |
dc.description.sponsorship | This work was funded in part by Welch Foundation grant number F-0003-19620604 (J.S.M). Argonne is operated by UChicago Argonne, LLC, for the US Department of Energy (DOE), Office of Biological and Environmental Research under Contract DE-AC02-06CH11357. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing Group | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Protein vaccines | es_ES |
dc.subject | Virology | es_ES |
dc.subject | X-ray crystallography | es_ES |
dc.title | Structure-based design of prefusion-stabilized human metapneumovirus fusion proteins | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 35288548 | es_ES |
dc.format.volume | 13 | es_ES |
dc.format.number | 1 | es_ES |
dc.format.page | 1299 | es_ES |
dc.identifier.doi | 10.1038/s41467-022-28931-3 | es_ES |
dc.contributor.funder | Welch Foundation | es_ES |
dc.contributor.funder | United States Department of Energy | es_ES |
dc.contributor.funder | University of Chicago (Estados Unidos) | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2041-1723 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1038/s41467-022-28931-3 | es_ES |
dc.identifier.journal | Nature Communications | es_ES |
dc.repisalud.centro | ISCIII | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.rights.accessRights | open access | es_ES |