Universität zu Köln

Kumar, Suresh, Koenig, Johannes, Schneider, Andreas, Wermeling, Fredrik ORCID: 0000-0001-9633-677X, Boddul, Sanjaykumar, Theobald, Sebastian J., Vollmer, Miriam, Kloos, Doreen, Lachmann, Nico ORCID: 0000-0002-4245-1497, Klawonn, Frank ORCID: 0000-0001-9613-182X, Lienenklaus, Stefan, Talbot, Steven R., Bleich, Andre, Wenzel, Nadine, von Kaisenberg, Constantin, Keck, James and Stripecke, Renata ORCID: 0000-0001-7756-8460 (2021). In Vivo Lentiviral Gene Delivery of HLA-DR and Vaccination of Humanized Mice for Improving the Human T and B Cell Immune Reconstitution. Biomedicines, 9 (8). BASEL: MDPI. ISSN 2227-9059

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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-alpha) and a human cytomegalovirus gB antigen (HCMV-gB). Humanized NOD/Ragl(null)/Th2R gamma(null) (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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kumar, Suresh UNSPECIFIED UNSPECIFIED UNSPECIFIED Koenig, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Wermeling, Fredrik UNSPECIFIED orcid.org/0000-0001-9633-677X UNSPECIFIED Boddul, Sanjaykumar UNSPECIFIED UNSPECIFIED UNSPECIFIED Theobald, Sebastian J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vollmer, Miriam UNSPECIFIED UNSPECIFIED UNSPECIFIED Kloos, Doreen UNSPECIFIED UNSPECIFIED UNSPECIFIED Lachmann, Nico UNSPECIFIED orcid.org/0000-0002-4245-1497 UNSPECIFIED Klawonn, Frank UNSPECIFIED orcid.org/0000-0001-9613-182X UNSPECIFIED Lienenklaus, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Talbot, Steven R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bleich, Andre UNSPECIFIED UNSPECIFIED UNSPECIFIED Wenzel, Nadine UNSPECIFIED UNSPECIFIED UNSPECIFIED von Kaisenberg, Constantin UNSPECIFIED UNSPECIFIED UNSPECIFIED Keck, James UNSPECIFIED UNSPECIFIED UNSPECIFIED Stripecke, Renata UNSPECIFIED orcid.org/0000-0001-7756-8460 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-597534
DOI:	10.3390/biomedicines9080961
Journal or Publication Title:	Biomedicines
Volume:	9
Number:	8
Date:	2021
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2227-9059
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MOUSE; MODEL; INDUCTION; VECTORS; SYSTEM Multiple languages Biochemistry & Molecular Biology; Medicine, Research & Experimental; Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59753