In Vivo Lentiviral Gene Delivery of HLA-DR and Vaccination of Humanized Mice for Improving the Human T and B Cell Immune Reconstitution.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Theobald, Sebastian J
Talbot, Steven R
von Kaisenberg, Constantin
MetadataShow full item record
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.
CitationBiomedicines. 2021 Aug 5;9(8):961. doi: 10.3390/biomedicines9080961.
AffiliationHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
The following license files are associated with this item:
- Creative Commons
- Expression of HLA class II molecules in humanized NOD.Rag1KO.IL2RgcKO mice is critical for development and function of human T and B cells.
- Authors: Danner R, Chaudhari SN, Rosenberger J, Surls J, Richie TL, Brumeanu TD, Casares S
- Issue date: 2011
- Integrase-defective lentiviral vectors encoding cytokines induce differentiation of human dendritic cells and stimulate multivalent immune responses in vitro and in vivo.
- Authors: Daenthanasanmak A, Salguero G, Borchers S, Figueiredo C, Jacobs R, Sundarasetty BS, Schneider A, Schambach A, Eiz-Vesper B, Blasczyk R, Weissinger EM, Ganser A, Stripecke R
- Issue date: 2012 Jul 20
- Visualization of the human CD4⁺ T-cell response in humanized HLA-DR4-expressing NOD/Shi-scid/γc(null) (NOG) mice by retrogenic expression of the human TCR gene.
- Authors: Takahashi T, Katano I, Ito R, Ito M
- Issue date: 2015 Jan 2
- Signatures of T and B Cell Development, Functional Responses and PD-1 Upregulation After HCMV Latent Infections and Reactivations in Nod.Rag.Gamma Mice Humanized With Cord Blood CD34(+) Cells.
- Authors: Theobald SJ, Khailaie S, Meyer-Hermann M, Volk V, Olbrich H, Danisch S, Gerasch L, Schneider A, Sinzger C, Schaudien D, Lienenklaus S, Riese P, Guzman CA, Figueiredo C, von Kaisenberg C, Spineli LM, Glaesener S, Meyer-Bahlburg A, Ganser A, Schmitt M, Mach M, Messerle M, Stripecke R
- Issue date: 2018
- Multidimensional Analysis Integrating Human T-Cell Signatures in Lymphatic Tissues with Sex of Humanized Mice for Prediction of Responses after Dendritic Cell Immunization.
- Authors: Volk V, Reppas AI, Robert PA, Spineli LM, Sundarasetty BS, Theobald SJ, Schneider A, Gerasch L, Deves Roth C, Klöss S, Koehl U, von Kaisenberg C, Figueiredo C, Hatzikirou H, Meyer-Hermann M, Stripecke R
- Issue date: 2017