Repertoire characterization and validation of gB-specific human IgGs directly cloned from humanized mice vaccinated with dendritic cells and protected against HCMV
Theobald SJ, Kreer C, Khailaie S, Bonifacius A, Eiz-Vesper B, Figueiredo C, Mach M, Backovic M, Ballmaier M, Koenig J, Olbrich H, Schneider A, Volk V, Danisch S, Gieselmann L, Ercanoglu MS, Messerle M, Kaisenberg Cv, Witte T, Klawonn F, Meyer-Hermann M, Klein F, Stripecke R (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 16
Pages Range: e1008560-
Journal Issue: 7
DOI: 10.1371/journal.ppat.1008560
Abstract
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.
Authors with CRIS profile
Additional Organisation(s)
Involved external institutions
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Germany (DE)
Universitätsklinikum Köln
Germany (DE)
Deutsches Zentrum für Infektionsforschung (DZIF)
Germany (DE)
Helmholtz-Zentrum für Infektionsforschung (HZI)
Germany (DE)
National Center for Scientific Research / Centre national de la recherche scientifique (CNRS)
France (FR)
Germany (DE)
Universitätsklinikum Köln
Germany (DE)
Deutsches Zentrum für Infektionsforschung (DZIF)
Germany (DE)
Helmholtz-Zentrum für Infektionsforschung (HZI)
Germany (DE)
National Center for Scientific Research / Centre national de la recherche scientifique (CNRS)
France (FR)
How to cite
APA:
Theobald, S.J., Kreer, C., Khailaie, S., Bonifacius, A., Eiz-Vesper, B., Figueiredo, C.,... Stripecke, R. (2020). Repertoire characterization and validation of gB-specific human IgGs directly cloned from humanized mice vaccinated with dendritic cells and protected against HCMV. PLoS Pathogens, 16(7), e1008560-. https://doi.org/10.1371/journal.ppat.1008560
MLA:
Theobald, Sebastian J., et al. "Repertoire characterization and validation of gB-specific human IgGs directly cloned from humanized mice vaccinated with dendritic cells and protected against HCMV." PLoS Pathogens 16.7 (2020): e1008560-.
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