title: A trifunctional dextran-based nanovaccine targets and activates murine dendritic cells, and induces potent cellular and humoral immune responses in vivo.
abstract: Dendritic cells (DCs) constitute an attractive target for specific delivery of nanovaccines for immunotherapeutic applications. Here we tested nano-sized dextran (DEX) particles to serve as a DC-addressing nanocarrier platform. Non-functionalized DEX particles had no immunomodulatory effect on bone marrow (BM)-derived murine DCs in vitro. However, when adsorbed with ovalbumine (OVA), DEX particles were efficiently engulfed by BM-DCs in a mannose receptor-dependent manner. A DEX-based nanovaccine containing OVA and lipopolysaccharide (LPS) as a DC stimulus induced strong OVA peptide-specific CD4(+) and CD8(+) T cell proliferation both in vitro and upon systemic application in mice, as well as a robust OVA-specific humoral immune response (IgG1>IgG2a) in vivo. Accordingly, this nanovaccine also raised both a more pronounced delayed-type hypersensitivity response and a stronger induction of cytotoxic CD8(+) T cells than obtained upon administration of OVA and LPS in soluble form. Therefore, DEX-based nanoparticles constitute a potent, versatile and easy to prepare nanovaccine platform for immunotherapeutic approaches.
authors: Department of Dermatology, University Medical Center Mainz, Mainz, Germany.
authors: Limei
authors: L
authors: Shen
authors: Tetsuya
authors: T
authors: Higuchi
authors: Ingrid
authors: I
authors: Tubbe
authors: Nicole
authors: N
authors: Voltz
authors: Mathias
authors: M
authors: Krummen
authors: Stefanie
authors: S
authors: Pektor
authors: Evelyn
authors: E
authors: Montermann
authors: Kristin
authors: K
authors: Rausch
authors: Manfred
authors: M
authors: Schmidt
authors: Hansjörg
authors: H
authors: Schild
authors: Stephan
authors: S
authors: Grabbe
authors: Matthias
authors: M
authors: Bros
mesh_terms: D000327:Adsorption; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D003911:Dextrans / Q000737:chemistry / Q000276:immunology*; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D037181:Lectins, C-Type / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles; D010047:Ovalbumin / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology; D014612:Vaccines / Q000737:chemistry* / Q000276:immunology*
chemical_list: D003911:Dextrans; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D014612:Vaccines; D010047:Ovalbumin