Repertoire characterization and validation of gB-specific human IgGs directly cloned from humanized mice vaccinated with dendritic cells and protected against HCMV.
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Authors
Theobald, Sebastian JKreer, Christoph
Khailaie, Sahamoddin
Bonifacius, Agnes
Eiz-Vesper, Britta
Figueiredo, Constanca
Mach, Michael
Backovic, Marija
Ballmaier, Matthias
Koenig, Johannes
Olbrich, Henning
Schneider, Andreas
Volk, Valery
Danisch, Simon
Gieselmann, Lutz
Ercanoglu, Meryem Seda
Messerle, Martin
Kaisenberg, Constantin von
Witte, Torsten
Klawonn, Frank

Meyer-Hermann, Michael

Klein, Florian
Stripecke, Renata
Issue Date
2020-07-15
Metadata
Show full item recordAbstract
Human 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.Citation
PLoS Pathog. 2020 Jul 15;16(7):e1008560. doi: 10.1371/journal.ppat.1008560.Affiliation
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.Journal
PLoS pathogensPubMed ID
32667948Type
ArticleLanguage
enEISSN
1553-7374ae974a485f413a2113503eed53cd6c53
10.1371/journal.ppat.1008560
Scopus Count
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- Creative Commons
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