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dc.contributor.authorKumar, Suresh
dc.contributor.authorKoenig, Johannes
dc.contributor.authorSchneider, Andreas
dc.contributor.authorWermeling, Fredrik
dc.contributor.authorBoddul, Sanjaykumar
dc.contributor.authorTheobald, Sebastian J
dc.contributor.authorVollmer, Miriam
dc.contributor.authorKloos, Doreen
dc.contributor.authorLachmann, Nico
dc.contributor.authorKlawonn, Frank
dc.contributor.authorLienenklaus, Stefan
dc.contributor.authorTalbot, Steven R
dc.contributor.authorBleich, André
dc.contributor.authorWenzel, Nadine
dc.contributor.authorvon Kaisenberg, Constantin
dc.contributor.authorKeck, James
dc.contributor.authorStripecke, Renata
dc.date.accessioned2021-09-15T13:16:30Z
dc.date.available2021-09-15T13:16:30Z
dc.date.issued2021-08-05
dc.identifier.citationBiomedicines. 2021 Aug 5;9(8):961. doi: 10.3390/biomedicines9080961.en_US
dc.identifier.issn2227-9059
dc.identifier.pmid34440166
dc.identifier.doi10.3390/biomedicines9080961
dc.identifier.urihttp://hdl.handle.net/10033/623033
dc.description.abstractHumanized mouse models generated with human hematopoietic stem cells (HSCs) and reconstituting the human immune system (HIS-mice) are invigorating preclinical testing of vaccines and immunotherapies. We have recently shown that human engineered dendritic cells boosted bonafide human T and B cell maturation and antigen-specific responses in HIS-mice. Here, we evaluated a cell-free system based on in vivo co-delivery of lentiviral vectors (LVs) for expression of a human leukocyte antigen (HLA-DRA*01/ HLA-DRB1*0401 functional complex, "DR4"), and a LV vaccine expressing human cytokines (GM-CSF and IFN-α) and a human cytomegalovirus gB antigen (HCMV-gB). Humanized NOD/Rag1null/IL2Rγnull (NRG) mice injected by i.v. with LV-DR4/fLuc showed long-lasting (up to 20 weeks) vector distribution and expression in the spleen and liver. In vivo administration of the LV vaccine after LV-DR4/fLuc delivery boosted the cellularity of lymph nodes, promoted maturation of terminal effector CD4+ T cells, and promoted significantly higher development of IgG+ and IgA+ B cells. This modular lentigenic system opens several perspectives for basic human immunology research and preclinical utilization of LVs to deliver HLAs into HIS-mice.en_US
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectB cell maturationen_US
dc.subjectHLA matchen_US
dc.subjectIgGen_US
dc.subjectclass-switchen_US
dc.subjectcytomegalovirusen_US
dc.subjecthumanized miceen_US
dc.subjectlentiviral vectoren_US
dc.subjectstem cell transplantationen_US
dc.subjectvaccineen_US
dc.titleIn Vivo Lentiviral Gene Delivery of HLA-DR and Vaccination of Humanized Mice for Improving the Human T and B Cell Immune Reconstitution.en_US
dc.typeArticleen_US
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalBiomedicinesen_US
dc.source.volume9
dc.source.issue8
refterms.dateFOA2021-09-15T13:16:31Z
dc.source.journaltitleBiomedicines
dc.source.countrySwitzerland


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International