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dc.contributor.author | Gilman, Morgan S A | |
dc.contributor.author | Moin, Syed M | |
dc.contributor.author | Mas-Lloret, Vicente | |
dc.contributor.author | Chen, Man | |
dc.contributor.author | Patel, Nita K | |
dc.contributor.author | Kramer, Kari | |
dc.contributor.author | Zhu, Qing | |
dc.contributor.author | Kabeche, Stephanie C | |
dc.contributor.author | Kumar, Azad | |
dc.contributor.author | Palomo-Sanz, Concepcion | |
dc.contributor.author | Beaumont, Tim | |
dc.contributor.author | Baxa, Ulrich | |
dc.contributor.author | Ulbrandt, Nancy D | |
dc.contributor.author | Melero, Jose Antonio | |
dc.contributor.author | Graham, Barney S | |
dc.contributor.author | McLellan, Jason S | |
dc.date.accessioned | 2020-05-07T07:14:24Z | |
dc.date.available | 2020-05-07T07:14:24Z | |
dc.date.issued | 2015-07 | |
dc.identifier.citation | PLoS Pathog. 2015 Jul 10;11(7):e1005035. | es_ES |
dc.identifier.issn | 1553-7374 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/9936 | |
dc.description.abstract | Prevention 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.sponsorship | Data 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.iso | eng | es_ES |
dc.publisher | Public Library of Science (PLOS) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | Antibodies, Neutralizing | es_ES |
dc.subject.mesh | Antibodies, Viral | es_ES |
dc.subject.mesh | Antigens, Viral | es_ES |
dc.subject.mesh | Cell Line | es_ES |
dc.subject.mesh | Chromatography, Gel | es_ES |
dc.subject.mesh | Crystallography, X-Ray | es_ES |
dc.subject.mesh | Enzyme-Linked Immunosorbent Assay | es_ES |
dc.subject.mesh | Epitope Mapping | es_ES |
dc.subject.mesh | Epitopes, B-Lymphocyte | es_ES |
dc.subject.mesh | Flow Cytometry | es_ES |
dc.subject.mesh | Glycoproteins | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Protein Structure, Quaternary | es_ES |
dc.subject.mesh | Respiratory Syncytial Viruses | es_ES |
dc.subject.mesh | Surface Plasmon Resonance | es_ES |
dc.title | Characterization of a Prefusion-Specific Antibody That Recognizes a Quaternary, Cleavage-Dependent Epitope on the RSV Fusion Glycoprotein | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 26161532 | es_ES |
dc.format.volume | 11 | es_ES |
dc.format.number | 7 | es_ES |
dc.format.page | e1005035 | es_ES |
dc.identifier.doi | 10.1371/journal.ppat.1005035 | es_ES |
dc.contributor.funder | Cancer Resarch Institute (Estados Unidos) | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | NIH - National Institute of Allergy and Infectious Diseases (NIAID) (Estados Unidos) | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1553-7374 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1371/journal.ppat.1005035 | es_ES |
dc.identifier.journal | PLoS pathogens | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Microbiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/DMR-1332208 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/NIGMS GM-103485 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/DE-AC02-06CH11357 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/HHSN261200800001E | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/SAF2012-31217 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/1R43AI112124 | es_ES |
dc.rights.accessRights | open access | es_ES |