Shen Limei, Higuchi Tetsuya, Tubbe Ingrid, Voltz Nicole, Krummen Mathias, Pektor Stefanie, Montermann Evelyn, Rausch Kristin, Schmidt Manfred, Schild Hansjörg, Grabbe Stephan, Bros Matthias
Department of Dermatology, University Medical Center Mainz, Mainz, Germany.
PLoS One. 2013 Dec 5;8(12):e80904. doi: 10.1371/journal.pone.0080904. eCollection 2013.
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.
树突状细胞（DCs）是免疫治疗应用中纳米疫苗特异性递送的一个有吸引力的靶点。在此，我们测试了纳米级葡聚糖（DEX）颗粒作为一种靶向DC的纳米载体平台。未功能化的DEX颗粒在体外对源自骨髓（BM）的小鼠DCs没有免疫调节作用。然而，当吸附卵清蛋白（OVA）时，DEX颗粒以甘露糖受体依赖性方式被BM-DCs有效吞噬。一种基于DEX的纳米疫苗，包含OVA和脂多糖（LPS）作为DC刺激物，在体外以及在小鼠全身应用后均能诱导强烈的OVA肽特异性CD4(+)和CD8(+) T细胞增殖，并且在体内引发强大的OVA特异性体液免疫反应（IgG1>IgG2a）。因此，与以可溶形式给予OVA和LPS相比，这种纳米疫苗还引发了更明显的迟发型超敏反应以及更强的细胞毒性CD8(+) T细胞诱导。所以，基于DEX的纳米颗粒构成了一种用于免疫治疗方法的有效、通用且易于制备的纳米疫苗平台。
