6533b7dafe1ef96bd126d954
RESEARCH PRODUCT
A trifunctional dextran-based nanovaccine targets and activates murine dendritic cells, and induces potent cellular and humoral immune responses in vivo.
Limei ShenTetsuya HiguchiIngrid TubbeNicole VoltzMathias KrummenStefanie PektorEvelyn MontermannKristin RauschManfred SchmidtHansjörg SchildStephan GrabbeMatthias Brossubject
CD4-Positive T-LymphocytesLipopolysaccharidesOvalbumin610 Medizinlcsh:MedicineBone Marrow CellsReceptors Cell SurfaceCD8-Positive T-LymphocytesMiceTh2 Cells610 Medical sciencesAnimalsLectins C-Typelcsh:ScienceCell ProliferationImmunity CellularVaccineslcsh:RDextransDendritic CellsImmunity HumoralMannose-Binding LectinsNanoparticleslcsh:QAdsorptionMannose ReceptorResearch Articledescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2013-12-01 | PLoS ONE |