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dc.creatorCardoso, Francisco Miguel-
dc.creatorIbañez, Lorena Itatí-
dc.creatorVan Den Hoecke, Silvie-
dc.creatorDe Baets, Sarah-
dc.creatorSmet, Anouk-
dc.creatorRoose, Kenny-
dc.creatorSchepens, Bert-
dc.creatorDescamps, Francis J.-
dc.creatorFiers, Walter-
dc.creatorMuyldermans, Serge-
dc.creatorDepicker, Ann-
dc.creatorSaelens, Xavier-
dc.date2016-02-11T19:52:31Z-
dc.date2016-02-11T19:52:31Z-
dc.date2014-05-
dc.date2016-03-30 10:35:44.97925-03-
dc.date.accessioned2019-04-29T15:51:40Z-
dc.date.available2019-04-29T15:51:40Z-
dc.date.issued2014-05-
dc.identifierCardoso, Francisco Miguel; Ibañez, Lorena Itatí; Van Den Hoecke, Silvie; De Baets, Sarah; Smet, Anouk; et al.; Single domain antibodies targeting neuraminidase protect against an H5N1 influenza virus challenge; American Society for Microbiology; Journal of Virology; 88; 15; 5-2014; 8278-8296-
dc.identifier0022-538X-
dc.identifierhttp://hdl.handle.net/11336/4154-
dc.identifier.urihttp://rodna.bn.gov.ar:8080/jspui/handle/bnmm/303965-
dc.descriptionInfluenza virus neuraminidase (NA) is an interesting target of small-molecule antiviral drugs. We isolated a set of H5N1 NAspecific single-domain antibodies (N1-VHHm) and evaluated their in vitro and in vivo antiviral potential. Two of them inhibited the NA activity and in vitro replication of clade 1 and 2 H5N1 viruses. We then generated bivalent derivatives of N1-VHHm by two methods. First, we made N1-VHHb by genetically joining two N1-VHHm moieties with a flexible linker. Second, bivalent N1-VHH-Fc proteins were obtained by genetic fusion of the N1-VHHm moiety with the crystallizable region of mouse IgG2a (Fc). The in vitro antiviral potency against H5N1 of both bivalent N1-VHHb formats was 30- to 240-fold higher than that of their monovalent counterparts, with 50% inhibitory concentrations in the low nanomolar range. Moreover, single-dose prophylactic treatment with bivalent N1-VHHb or N1-VHH-Fc protected BALB/c mice against a lethal challenge with H5N1 virus, including an oseltamivir-resistant H5N1 variant. Surprisingly, an N1-VHH-Fc fusion without in vitro NA-inhibitory or antiviral activity also protected mice against an H5N1 challenge. Virus escape selection experiments indicated that one amino acid residue close to the catalytic site is required for N1-VHHm binding. We conclude that single-domain antibodies directed against influenza virus NA protect against H5N1 virus infection, and when engineered with a conventional Fc domain, they can do so in the absence of detectable NA-inhibitory activity.-
dc.descriptionFil: Cardoso, Francisco Miguel. VIB Inflammation Research Center; Bélgica. Ghent University. Department for Biomedical Molecular Biology; Bélgica-
dc.descriptionFil: Ibañez, Lorena Itatí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencias y Tecnología "Dr. Cesar Milstein"; Argentina. VIB Inflammation Research Center; Bélgica. Ghent University. Department for Biomedical Molecular Biology; Bélgica-
dc.descriptionFil: Van Den Hoecke, Silvie. VIB Inflammation Research Center; Bélgica. Ghent University. Department for Biomedical Molecular Biology; Bélgica-
dc.descriptionFil: De Baets, Sarah. VIB Inflammation Research Center; Bélgica. Ghent University. Department for Biomedical Molecular Biology; Bélgica-
dc.descriptionFil: Smet, Anouk. VIB Inflammation Research Center; Bélgica. Ghent University. Department for Biomedical Molecular Biology; Bélgica-
dc.descriptionFil: Roose, Kenny. VIB Inflammation Research Center; Bélgica. Ghent University. Department for Biomedical Molecular Biology; Bélgica-
dc.descriptionFil: Schepens, Bert. VIB Inflammation Research Center; Bélgica. Ghent University. Department for Biomedical Molecular Biology; Bélgica-
dc.descriptionFil: Descamps, Francis J.. VIB Inflammation Research Center; Bélgica. Ghent University. Department for Biomedical Molecular Biology; Bélgica-
dc.descriptionFil: Fiers, Walter. VIB Inflammation Research Center; Bélgica. Ghent University. Department for Biomedical Molecular Biology; Bélgica-
dc.descriptionFil: Muyldermans, Serge. Structural Biology Research Center; Bélgica. Vrije Universiteit Brussel. Laboratory of Cellular and Molecular Immunology; Bélgica-
dc.descriptionFil: Depicker, Ann. VIB. Department of Plant Systems Biology; Bélgica. Department of Biotechnology and Bioinformatics; Bélgica-
dc.descriptionFil: Saelens, Xavier. VIB Inflammation Research Center; Bélgica. Ghent University. Department for Biomedical Molecular Biology; Bélgica-
dc.formatapplication/pdf-
dc.formatapplication/pdf-
dc.languageeng-
dc.publisherAmerican Society for Microbiology-
dc.relationinfo:eu-repo/semantics/altIdentifier/url/http://jvi.asm.org/content/88/15/8278.long-
dc.relationinfo:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135927/-
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1128%2FJVI.03178-13-
dc.relationinfo:eu-repo/semantics/altIdentifier/issn/0022-538X-
dc.rightsinfo:eu-repo/semantics/restrictedAccess-
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/-
dc.sourcereponame:CONICET Digital (CONICET)-
dc.sourceinstname:Consejo Nacional de Investigaciones Científicas y Técnicas-
dc.sourceinstacron:CONICET-
dc.subjectINFLUENZA A-
dc.subjectNANOBODY VHH-
dc.subjectNEURAMINIDASE-
dc.subjectANTIVIRAL-
dc.subjectVirología-
dc.subjectCiencias Biológicas-
dc.subjectCIENCIAS NATURALES Y EXACTAS-
dc.titleSingle domain antibodies targeting neuraminidase protect against an H5N1 influenza virus challenge-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.typeinfo:ar-repo/semantics/articulo-
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