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dc.contributor.authorOlmedillas Cela, Eduardo 
dc.contributor.authorCano, Olga 
dc.contributor.authorMartinez, Isidoro 
dc.contributor.authorLuque, Daniel 
dc.contributor.authorTerron-Orellana, Maria Carmen 
dc.contributor.authorMcLellan, Jason S
dc.contributor.authorMelero, Jose Antonio 
dc.contributor.authorMas-Lloret, Vicente
dc.identifier.citationEMBO Mol Med. 2018 Feb;10(2):175-187.es_ES
dc.description.abstractHuman respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV), two members of the Pneumoviridae family, account for the majority of severe lower respiratory tract infections worldwide in very young children. They are also a frequent cause of morbidity and mortality in the elderly and immunocompromised adults. High levels of neutralizing antibodies, mostly directed against the viral fusion (F) glycoprotein, correlate with protection against either hRSV or hMPV However, no cross-neutralization is observed in polyclonal antibody responses raised after virus infection or immunization with purified F proteins. Based on crystal structures of hRSV F and hMPV F, we designed chimeric F proteins in which certain residues of well-characterized antigenic sites were swapped between the two antigens. The antigenic changes were monitored by ELISA with virus-specific monoclonal antibodies. Inoculation of mice with these chimeras induced polyclonal cross-neutralizing antibody responses, and mice were protected against challenge with the virus used for grafting of the heterologous antigenic site. These results provide a proof of principle for chimeric fusion proteins as single immunogens that can induce cross-neutralizing antibody and protective responses against more than one human pneumovirus.es_ES
dc.description.sponsorshipWe would like to thank the personnel of the Genomics and the Animal House facilities at Instituto de Salud Carlos III for their help in part of the work here presented. This work was supported in part by grants SAF2015‐67033‐R (JAM), PI15CIII/00024 (IM) from Instituto de Salud Carlos III, BFU 2013‐43149‐R (DL) from Plan Nacional I+D+I,c, and P20GM113132 (JSM) from the National Institute of General Medical Sciences of the National Institutes of Health.es_ES
dc.publisherWiley es_ES
dc.subjectNeutralizing antibodieses_ES
dc.subjectStructure‐based designes_ES
dc.subjectUniversal vaccineses_ES
dc.subject.meshAnimals es_ES
dc.subject.meshAntibodies, Neutralizing es_ES
dc.subject.meshHumans es_ES
dc.subject.meshImmunization es_ES
dc.subject.meshMice es_ES
dc.subject.meshModels, Animal es_ES
dc.subject.meshRecombinant Fusion Proteins es_ES
dc.subject.meshVaccines, Synthetic es_ES
dc.subject.meshViral Fusion Proteins es_ES
dc.subject.meshViral Vaccines es_ES
dc.subject.meshMetapneumovirus es_ES
dc.subject.meshParamyxoviridae Infections es_ES
dc.subject.meshRespiratory Syncytial Virus Infections es_ES
dc.subject.meshRespiratory Syncytial Virus, Humanes_ES
dc.titleChimeric Pneumoviridae fusion proteins as immunogens to induce cross-neutralizing antibody responseses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderInstituto de Salud Carlos III 
dc.identifier.journalEMBO molecular medicinees_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/BFU 2013‐43149‐Res_ES
dc.rights.accessRightsopen accesses_ES

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Atribución 4.0 Internacional
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