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dc.contributor.authorMas-Lloret, Vicente 
dc.contributor.authorRodriguez, Laura 
dc.contributor.authorOlmedillas, Eduardo 
dc.contributor.authorCano, Olga 
dc.contributor.authorPalomo-Sanz, Concepcion 
dc.contributor.authorTerrón, María C
dc.contributor.authorLuque, Daniel 
dc.contributor.authorMelero, Jose Antonio 
dc.contributor.authorMcLellan, Jason S
dc.date.accessioned2018-12-12T14:30:41Z
dc.date.available2018-12-12T14:30:41Z
dc.date.issued2016-09-09
dc.identifier.citationPLoS Pathog. 2016 Sep 9;12(9):e1005859.es_ES
dc.identifier.issn1553-7374es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6825
dc.description.abstractHuman metapneumovirus (hMPV) is a paramyxovirus that is a common cause of bronchiolitis and pneumonia in children less than five years of age. The hMPV fusion (F) glycoprotein is the primary target of neutralizing antibodies and is thus a critical vaccine antigen. To facilitate structure-based vaccine design, we stabilized the ectodomain of the hMPV F protein in the postfusion conformation and determined its structure to a resolution of 3.3 Å by X-ray crystallography. The structure resembles an elongated cone and is very similar to the postfusion F protein from the related human respiratory syncytial virus (hRSV). In contrast, significant differences were apparent with the postfusion F proteins from other paramyxoviruses, such as human parainfluenza type 3 (hPIV3) and Newcastle disease virus (NDV). The high similarity of hMPV and hRSV postfusion F in two antigenic sites targeted by neutralizing antibodies prompted us to test for antibody cross-reactivity. The widely used monoclonal antibody 101F, which binds to antigenic site IV of hRSV F, was found to cross-react with hMPV postfusion F and neutralize both hRSV and hMPV. Despite the cross-reactivity of 101F and the reported cross-reactivity of two other antibodies, 54G10 and MPE8, we found no detectable cross-reactivity in the polyclonal antibody responses raised in mice against the postfusion forms of either hMPV or hRSV F. The postfusion-stabilized hMPV F protein did, however, elicit high titers of hMPV-neutralizing activity, suggesting that it could serve as an effective subunit vaccine. Structural insights from these studies should be useful for designing novel immunogens able to induce wider cross-reactive antibody responses.es_ES
dc.description.sponsorshipThis work was supported in part by grants SAF2015-67033-RSAF2012-31217 (JAM) and BFU 2013-43149-R (DL) from Plan Nacional I+D+i and by grant P20GM113132 (JSM) from the National Institute of General Medical Sciences of the National Institutes of Health. Results shown in this report are derived from work performed at Argonne National Laboratory, Structural Biology Center at the Advanced Photon Source. Argonne is operated by UChicago Argonne, LLC, for the U.S. Department of Energy, Office of Biological and Environmental Research under contract DE-AC02-06CH11357. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.es_ES
dc.language.isoenges_ES
dc.publisherPublic Library of Sciencees_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshAmino Acid Sequence es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshAntibodies, Monoclonal es_ES
dc.subject.meshAntibodies, Neutralizing es_ES
dc.subject.meshAntibodies, Viral es_ES
dc.subject.meshAntigens, Viral es_ES
dc.subject.meshCross Reactions es_ES
dc.subject.meshCrystallography, X-Ray es_ES
dc.subject.meshFemale es_ES
dc.subject.meshGenetic Engineering es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMetapneumovirus es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Inbred BALB C es_ES
dc.subject.meshModels, Moleculares_ES
dc.subject.meshMolecular Conformation es_ES
dc.subject.meshRespiratory Syncytial Virus, Humanes_ES
dc.subject.meshSequence Alignment es_ES
dc.subject.meshViral Fusion Proteins es_ES
dc.titleEngineering, Structure and Immunogenicity of the Human Metapneumovirus F Protein in the Postfusion Conformationes_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID27611367es_ES
dc.format.volume12es_ES
dc.format.number9es_ES
dc.format.pagee1005859es_ES
dc.identifier.doi10.1371/journal.ppat.1005859es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderNational Institutes of Health (United States)es_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1553-7374es_ES
dc.relation.publisherversionhttps://doi.org/10.1371/journal.ppat.1005859es_ES
dc.identifier.journalPLoS pathogenses_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2015-67033-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2012-31217es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BFU 2013-43149-Res_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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Atribución 4.0 Internacional
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