Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China.
National Glycoengineering Research Center, Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Jinan, China.
Carbohydr Polym. 2019 Jun 1;213:100-111. doi: 10.1016/j.carbpol.2019.02.093. Epub 2019 Feb 26.
Nasal immunization to prevent and treat diseases caused by infection through the respiratory tract cannot be actualized because of the lack of effective adjuvants. We have proven that compared with antigens loaded on CS or O-HTCC alone in nasal vaccination, antigens loaded on the nanoparticles of curdlan sulfate/O-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (CS/O-HTCC) can induce stronger systemic and mucosal immune responses. In this study, we evaluated the immunostimulatory activity and mechanisms of CS/O-HTCC nanoparticles. The results showed that CS/O-HTCC nanoparticles can improve the activation of antigen-presenting cells, upregulate the production of inflammatory factors and cytokines, induce cross-presentation, and simultaneously activate type I interferon-related genes. CS/O-HTCC nanoparticles also activated the PI3K/AKT and MAPK pathways and significantly promoted IL-2 transcription to induce the proliferation of lymphocytes. The results revealed that CS/O-HTCC nanoparticles as a type of multifunctional adjuvant can improve multiple arms of immune responses.
鼻腔免疫接种可以预防和治疗通过呼吸道感染引起的疾病,但由于缺乏有效的佐剂,目前还无法实现。我们已经证明,与鼻腔免疫接种中单独负载于壳聚糖(CS)或 O-羟丙基三甲基氯化铵壳聚糖(O-HTCC)上的抗原相比,负载于硫酸几丁聚糖(Curdlan sulfate)/O-(2-羟丙基)-3-三甲基氯化铵壳聚糖(CS/O-HTCC)纳米粒子上的抗原可以诱导更强的全身和黏膜免疫应答。在这项研究中,我们评估了 CS/O-HTCC 纳米粒子的免疫刺激活性和机制。结果表明,CS/O-HTCC 纳米粒子可以改善抗原呈递细胞的激活,上调炎症因子和细胞因子的产生,诱导交叉呈递,同时激活 I 型干扰素相关基因。CS/O-HTCC 纳米粒子还激活了 PI3K/AKT 和 MAPK 通路,并显著促进了 IL-2 的转录,从而诱导淋巴细胞的增殖。结果表明,CS/O-HTCC 纳米粒子作为一种多功能佐剂,可以改善多种免疫反应途径。