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dc.contributor.authorGilman, Morgan S A
dc.contributor.authorCastellanos, Carlos A
dc.contributor.authorChen, Man
dc.contributor.authorNgwuta, Joan O
dc.contributor.authorGoodwin, Eileen
dc.contributor.authorMoin, Syed M
dc.contributor.authorMas-Lloret, Vicente 
dc.contributor.authorMelero, Jose Antonio 
dc.contributor.authorWright, Peter F
dc.contributor.authorGraham, Barney S
dc.contributor.authorMcLellan, Jason S
dc.contributor.authorWalker, Laura M
dc.date.accessioned2020-05-07T07:11:59Z
dc.date.available2020-05-07T07:11:59Z
dc.date.issued2016-12-16
dc.identifier.citationSci Immunol. 2016 Dec 16;1(6). pii: eaaj1879.es_ES
dc.identifier.issn2470-9468es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/9935
dc.description.abstractRespiratory syncytial virus (RSV) causes substantial morbidity and mortality in young children and the elderly. There are currently no licensed RSV vaccines, and passive prophylaxis with the monoclonal antibody palivizumab is restricted to high-risk infants in part due to its modest efficacy. Although it is widely agreed that an effective RSV vaccine will require the induction of a potent neutralizing antibody response against the RSV fusion (F) glycoprotein, little is known about the specificities and functional activities of RSV F-specific antibodies induced by natural infection. Here, we have comprehensively profiled the human antibody response to RSV F by isolating and characterizing 364 RSV F-specific monoclonal antibodies from the memory B cells of three healthy adult donors. In all donors, the antibody response to RSV F is comprised of a broad diversity of clones that target several antigenic sites. Nearly half of the most potent antibodies target a previously undefined site of vulnerability near the apex of the prefusion conformation of RSV F (preF), providing strong support for the development of RSV vaccine candidates that preserve the membrane-distal hemisphere of the preF protein. Additionally, the antibodies targeting this new site display convergent sequence features, thus providing a future means to rapidly detect the presence of these antibodies in human vaccine samples. Many of the antibodies that bind preF-specific surfaces are over 100 times more potent than palivizumab, and several cross-neutralize human metapneumovirus (HMPV). Taken together, the results have implications for the design and evaluation of RSV vaccine candidates and offer new options for passive prophylaxis.es_ES
dc.description.sponsorshipWe thank Tushar Jain for guidance on statistical analyses, Todd Boland for assistance with antibody sequence analysis, Emilie Shipman for assistance with protein expression, Wen Li for technical assistance, Cody Williams and S.M. Eagol for assistance with figure preparation, and Margaret Ackerman for use of the magnetic microplate washer (BioTek) and the FLEXMAP 3D flow cytometer (Luminex). PBMC processing was carried out in DartLab, the Immune Monitoring and Flow Cytometry Shared Resource, supported by a National Cancer Institute Cancer Center Support Grant to the Norris Cotton Cancer Center (P30CA023108-37) and an Immunology COBRE Grant (P30GM103415-15) from the National Institute of General Medical Sciences. All the IgGs were sequenced by Adimab's Molecular Core and produced by the High Throughput Expression group. Biolayer interferometry binding experiments were performed by Adimab's protein analytics group. Funding: Support for this work was provided by the National Institute of General Medical Sciences of the National Institutes of Health award T32GM008704 (M.S.A.G.) and P20GM113132 (J.S.M.) and intramural funding from the National Institute of Allergy and Infectious Diseases to support work at the Vaccine Research Center (B.S.G.). This work was partially supported by grant SAF2015-67033-R to J.A.M. from Plan Nacional I+D+i.es_ES
dc.language.isoenges_ES
dc.publisherAmerican Association for the Advancement of Science (AAAS) es_ES
dc.type.hasVersionAMes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleRapid profiling of RSV antibody repertoires from the memory B cells of naturally infected adult donorses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID28111638es_ES
dc.format.volume1es_ES
dc.format.number6es_ES
dc.format.pageeaaj1879es_ES
dc.identifier.doi10.1126/sciimmunol.aaj1879es_ES
dc.contributor.funderNIH - National Cancer Institute (NCI) (Estados Unidos) 
dc.contributor.funderNIH - National Institute of General Medical Sciences (NIGMS) (Estados Unidos) 
dc.contributor.funderNIH - National Institute of Allergy and Infectious Diseases (NIAID) (Estados Unidos) 
dc.description.peerreviewedes_ES
dc.relation.publisherversionhttps://doi.org/10.1126/sciimmunol.aaj1879es_ES
dc.identifier.journalScience immunologyes_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/P30CA023108-37es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/P30GM103415-15es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/T32GM008704es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/ P20GM113132es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/SAF2015-67033-Res_ES
dc.rights.accessRightsopen accesses_ES


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