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dc.contributor.authorHsieh, Ching-Lin
dc.contributor.authorRush, Scott A
dc.contributor.authorPalomo-Sanz, Concepcion 
dc.contributor.authorChou, Chia-Wei
dc.contributor.authorPickens, Whitney
dc.contributor.authorMas-Lloret, Vicente 
dc.contributor.authorMcLellan, Jason S
dc.date.accessioned2022-05-24T06:51:58Z
dc.date.available2022-05-24T06:51:58Z
dc.date.issued2022-03-14
dc.identifier.citationNat Commun. 2022 Mar 14;13(1):1299.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/14467
dc.description.abstractThe 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.sponsorshipThis 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.isoenges_ES
dc.publisherNature Publishing Group es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectProtein vaccineses_ES
dc.subjectVirologyes_ES
dc.subjectX-ray crystallographyes_ES
dc.titleStructure-based design of prefusion-stabilized human metapneumovirus fusion proteinses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID35288548es_ES
dc.format.volume13es_ES
dc.format.number1es_ES
dc.format.page1299es_ES
dc.identifier.doi10.1038/s41467-022-28931-3es_ES
dc.contributor.funderWelch Foundation es_ES
dc.contributor.funderUnited States Department of Energy es_ES
dc.contributor.funderUniversity of Chicago (Estados Unidos)es_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn2041-1723es_ES
dc.relation.publisherversionhttps://doi.org/10.1038/s41467-022-28931-3es_ES
dc.identifier.journalNature Communicationses_ES
dc.repisalud.centroISCIIIes_ES
dc.repisalud.institucionISCIIIes_ES
dc.rights.accessRightsopen accesses_ES


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Atribución 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Atribución 4.0 Internacional