A Trifunctional Dextran-Based Nanovaccine Targets and Activates Murine Dendritic Cells, and Induces Potent Cellular and Humoral Immune Responses In Vivo

作者：Shen Limei; Higuchi Tetsuya; Tubbe Ingrid; Voltz Nicole; Krummen Mathias; Pektor Stefanie; Montermann Evelyn; Rausch Kristin; Schmidt Manfred; Schild Hansjoerg; Grabbe Stephan^*; Bros Matthias

来源：PLos One, 2013, 8(12): e80904.

DOI：10.1371/journal.pone.0080904

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%26gt;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.

• 出版日期2013-12-5