Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei City 11490, Taiwan, ROC; Institute of Preventive Medicine, National Defense Medical Center, New Taipei City 23742, Taiwan, ROC.
Institute of Preventive Medicine, National Defense Medical Center, New Taipei City 23742, Taiwan, ROC.
Carbohydr Polym. 2020 May 15;236:116041. doi: 10.1016/j.carbpol.2020.116041. Epub 2020 Feb 19.
Fucoidan/trimethylchitosan nanoparticles (FUC-TMC-NPs) have the potential to improve the immunostimulating efficiency of anthrax vaccine adsorbed (AVA). FUC-TMC-NPs with positive (+) or negative (-) surface charges were prepared via polyelectrolyte complexation, both charged NP types permitted high viability and presented no cytotoxicity on L929, A549 and JAWS II dendritic cells. Flow cytometry measurements indicated lower (+)-FUC-TMC-NPs internalization levels than (-)-FUC-TMC-NPs, yet produced high levels of pro-inflammatory cytokines IFN-γ, IL12p40, and IL-4. Moreover, fluorescence microscope images proved that both charged NP could deliver drugs into the nucleus. In vivo studies on A/J mice showed that (+)-FUC-TMC-NPs carrying AVA triggered an efficient response with a higher IgG anti-PA antibody titer than AVA with CpG oligodeoxynucleotides, and yielded 100 % protection when challenged with the anthracis spores. Furthermore, PA-specific IgG1 and IgG2a analysis confirmed that (+)-FUC-TMC-NPs strongly stimulated humoral immunity. In conclusion, (+)-FUC-TMC-NP is promising anthrax vaccine adjuvant as an alternative to CpG.
藻酸/三甲基壳聚糖纳米粒（FUC-TMC-NPs）具有提高炭疽疫苗吸附（AVA）免疫刺激效率的潜力。通过聚电解质络合作用制备带正（+）或负（-）表面电荷的 FUC-TMC-NPs，这两种带电 NP 类型都允许高存活率，并且对 L929、A549 和 JAWS II 树突状细胞没有细胞毒性。流式细胞术测量表明，+）-FUC-TMC-NPs 的内化水平低于（-）-FUC-TMC-NPs，但产生了高水平的促炎细胞因子 IFN-γ、IL12p40 和 IL-4。此外，荧光显微镜图像证明，两种带电 NP 都可以将药物递送到细胞核中。在 A/J 小鼠体内研究中，携带 AVA 的（+）-FUC-TMC-NPs 引发了高效反应，其 IgG 抗 PA 抗体滴度高于 CpG 寡脱氧核苷酸的 AVA，并且在受到炭疽孢子攻击时产生了 100%的保护。此外，PA 特异性 IgG1 和 IgG2a 分析证实（+）-FUC-TMC-NPs 强烈刺激了体液免疫。总之，（+）-FUC-TMC-NP 是一种有前途的炭疽疫苗佐剂，可替代 CpG。
