In Vivo Lentiviral Gene Delivery of HLA-DR and Vaccination of Humanized Mice for Improving the Human T and B Cell Immune Reconstitution.
dc.contributor.author | Kumar, Suresh | |
dc.contributor.author | Koenig, Johannes | |
dc.contributor.author | Schneider, Andreas | |
dc.contributor.author | Wermeling, Fredrik | |
dc.contributor.author | Boddul, Sanjaykumar | |
dc.contributor.author | Theobald, Sebastian J | |
dc.contributor.author | Vollmer, Miriam | |
dc.contributor.author | Kloos, Doreen | |
dc.contributor.author | Lachmann, Nico | |
dc.contributor.author | Klawonn, Frank | |
dc.contributor.author | Lienenklaus, Stefan | |
dc.contributor.author | Talbot, Steven R | |
dc.contributor.author | Bleich, André | |
dc.contributor.author | Wenzel, Nadine | |
dc.contributor.author | von Kaisenberg, Constantin | |
dc.contributor.author | Keck, James | |
dc.contributor.author | Stripecke, Renata | |
dc.date.accessioned | 2021-09-15T13:16:30Z | |
dc.date.available | 2021-09-15T13:16:30Z | |
dc.date.issued | 2021-08-05 | |
dc.identifier.citation | Biomedicines. 2021 Aug 5;9(8):961. doi: 10.3390/biomedicines9080961. | en_US |
dc.identifier.issn | 2227-9059 | |
dc.identifier.pmid | 34440166 | |
dc.identifier.doi | 10.3390/biomedicines9080961 | |
dc.identifier.uri | http://hdl.handle.net/10033/623033 | |
dc.description.abstract | Humanized 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.iso | en | en_US |
dc.publisher | MDPI | en_US |
dc.rights | Attribution 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | B cell maturation | en_US |
dc.subject | HLA match | en_US |
dc.subject | IgG | en_US |
dc.subject | class-switch | en_US |
dc.subject | cytomegalovirus | en_US |
dc.subject | humanized mice | en_US |
dc.subject | lentiviral vector | en_US |
dc.subject | stem cell transplantation | en_US |
dc.subject | vaccine | en_US |
dc.title | In 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.type | Article | en_US |
dc.contributor.department | HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. | en_US |
dc.identifier.journal | Biomedicines | en_US |
dc.source.volume | 9 | |
dc.source.issue | 8 | |
refterms.dateFOA | 2021-09-15T13:16:31Z | |
dc.source.journaltitle | Biomedicines | |
dc.source.country | Switzerland |