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dc.contributor.authorGilman, Morgan S A
dc.contributor.authorMoin, Syed M
dc.contributor.authorMas-Lloret, Vicente 
dc.contributor.authorChen, Man
dc.contributor.authorPatel, Nita K
dc.contributor.authorKramer, Kari
dc.contributor.authorZhu, Qing
dc.contributor.authorKabeche, Stephanie C
dc.contributor.authorKumar, Azad
dc.contributor.authorPalomo-Sanz, Concepcion 
dc.contributor.authorBeaumont, Tim
dc.contributor.authorBaxa, Ulrich
dc.contributor.authorUlbrandt, Nancy D
dc.contributor.authorMelero, Jose Antonio 
dc.contributor.authorGraham, Barney S
dc.contributor.authorMcLellan, Jason S
dc.date.accessioned2020-05-07T07:14:24Z
dc.date.available2020-05-07T07:14:24Z
dc.date.issued2015-07
dc.identifier.citationPLoS Pathog. 2015 Jul 10;11(7):e1005035.es_ES
dc.identifier.issn1553-7374es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/9936
dc.description.abstractPrevention efforts for respiratory syncytial virus (RSV) have been advanced due to the recent isolation and characterization of antibodies that specifically recognize the prefusion conformation of the RSV fusion (F) glycoprotein. These potently neutralizing antibodies are in clinical development for passive prophylaxis and have also aided the design of vaccine antigens that display prefusion-specific epitopes. To date, prefusion-specific antibodies have been shown to target two antigenic sites on RSV F, but both of these sites are also present on monomeric forms of F. Here we present a structural and functional characterization of human antibody AM14, which potently neutralized laboratory strains and clinical isolates of RSV from both A and B subtypes. The crystal structure and location of escape mutations revealed that AM14 recognizes a quaternary epitope that spans two protomers and includes a region that undergoes extensive conformational changes in the pre- to postfusion F transition. Binding assays demonstrated that AM14 is unique in its specific recognition of trimeric furin-cleaved prefusion F, which is the mature form of F on infectious virions. These results demonstrate that the prefusion F trimer contains potent neutralizing epitopes not present on monomers and that AM14 should be particularly useful for characterizing the conformational state of RSV F-based vaccine antigens.es_ES
dc.description.sponsorshipData collection at CHESS is supported by the NSF & NIH/NIGMS via NSF award DMR-1332208, and the MacCHESS resource is supported by NIH/NIGMS award GM-103485. Results shown in this report were also 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. Work performed by UB was funded in part with Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract HHSN261200800001E. NKP, KK, QZ and NDU were employed by MedImmune Inc, which funded the data collection and analysis of their experiments (neutralization assays, MARM isolation and affinity of D25 for peptide). JAM received funding from “Plan Nacional I+D+I” (Ministerio de Economía y Competitividad), grant SAF2012-31217. BSG was supported by funding from the intramural program of the National Institute of Allergy and Infectious Diseases. JSM received funding from the National Institutes of Health, grant 1R43AI112124. With the exception of MedImmune’s involvement stated above, 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 Science (PLOS) es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshAntibodies, Neutralizing es_ES
dc.subject.meshAntibodies, Viral es_ES
dc.subject.meshAntigens, Viral es_ES
dc.subject.meshCell Line es_ES
dc.subject.meshChromatography, Gel es_ES
dc.subject.meshCrystallography, X-Ray es_ES
dc.subject.meshEnzyme-Linked Immunosorbent Assay es_ES
dc.subject.meshEpitope Mapping es_ES
dc.subject.meshEpitopes, B-Lymphocyte es_ES
dc.subject.meshFlow Cytometry es_ES
dc.subject.meshGlycoproteins es_ES
dc.subject.meshHumans es_ES
dc.subject.meshProtein Structure, Quaternary es_ES
dc.subject.meshRespiratory Syncytial Viruses es_ES
dc.subject.meshSurface Plasmon Resonance es_ES
dc.titleCharacterization of a Prefusion-Specific Antibody That Recognizes a Quaternary, Cleavage-Dependent Epitope on the RSV Fusion Glycoproteines_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID26161532es_ES
dc.format.volume11es_ES
dc.format.number7es_ES
dc.format.pagee1005035es_ES
dc.identifier.doi10.1371/journal.ppat.1005035es_ES
dc.contributor.funderCancer Resarch Institute (Estados Unidos) 
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderNIH - National Institute of Allergy and Infectious Diseases (NIAID) (Estados Unidos) 
dc.description.peerreviewedes_ES
dc.identifier.e-issn1553-7374es_ES
dc.relation.publisherversionhttps://doi.org/10.1371/journal.ppat.1005035es_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/DMR-1332208es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/NIGMS GM-103485es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/DE-AC02-06CH11357es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/HHSN261200800001Ees_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/SAF2012-31217es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/1R43AI112124es_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