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dc.contributor.authorTheobald, Sebastian J
dc.contributor.authorKreer, Christoph
dc.contributor.authorKhailaie, Sahamoddin
dc.contributor.authorBonifacius, Agnes
dc.contributor.authorEiz-Vesper, Britta
dc.contributor.authorFigueiredo, Constanca
dc.contributor.authorMach, Michael
dc.contributor.authorBackovic, Marija
dc.contributor.authorBallmaier, Matthias
dc.contributor.authorKoenig, Johannes
dc.contributor.authorOlbrich, Henning
dc.contributor.authorSchneider, Andreas
dc.contributor.authorVolk, Valery
dc.contributor.authorDanisch, Simon
dc.contributor.authorGieselmann, Lutz
dc.contributor.authorErcanoglu, Meryem Seda
dc.contributor.authorMesserle, Martin
dc.contributor.authorKaisenberg, Constantin von
dc.contributor.authorWitte, Torsten
dc.contributor.authorKlawonn, Frank
dc.contributor.authorMeyer-Hermann, Michael
dc.contributor.authorKlein, Florian
dc.contributor.authorStripecke, Renata
dc.date.accessioned2020-10-22T09:33:34Z
dc.date.available2020-10-22T09:33:34Z
dc.date.issued2020-07-15
dc.identifier.citationPLoS Pathog. 2020 Jul 15;16(7):e1008560. doi: 10.1371/journal.ppat.1008560.en_US
dc.identifier.pmid32667948
dc.identifier.doi10.1371/journal.ppat.1008560
dc.identifier.urihttp://hdl.handle.net/10033/622527
dc.description.abstractHuman cytomegalovirus (HCMV) causes serious complications to immune compromised hosts. Dendritic cells (iDCgB) expressing granulocyte-macrophage colony-stimulating factor, interferon-alpha and HCMV-gB were developed to promote de novo antiviral adaptive responses. Mice reconstituted with a human immune system (HIS) were immunized with iDCgB and challenged with HCMV, resulting into 93% protection. Immunization stimulated the expansion of functional effector memory CD8+ and CD4+ T cells recognizing gB. Machine learning analyses confirmed bone marrow T/CD4+, liver B/IgA+ and spleen B/IgG+ cells as predictive biomarkers of immunization (≈87% accuracy). CD8+ and CD4+ T cell responses against gB were validated. Splenic gB-binding IgM-/IgG+ B cells were sorted and analyzed at a single cell level. iDCgB immunizations elicited human-like IgG responses with a broad usage of various IgG heavy chain V gene segments harboring variable levels of somatic hypermutation. From this search, two gB-binding human monoclonal IgGs were generated that neutralized HCMV infection in vitro. Passive immunization with these antibodies provided proof-of-concept evidence of protection against HCMV infection. This HIS/HCMV in vivo model system supported the validation of novel active and passive immune therapies for future clinical translation.en_US
dc.language.isoenen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleRepertoire characterization and validation of gB-specific human IgGs directly cloned from humanized mice vaccinated with dendritic cells and protected against HCMV.en_US
dc.typeArticleen_US
dc.identifier.eissn1553-7374
dc.contributor.departmentBRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalPLoS pathogensen_US
dc.source.volume16
dc.source.issue7
dc.source.beginpagee1008560
dc.source.endpage
refterms.dateFOA2020-10-22T09:33:37Z
dc.source.journaltitlePLoS pathogens
dc.source.countryUnited States


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