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.
National Glycoengineering Research Center, Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Jinan, Shandong.
Int J Nanomedicine. 2018 Apr 18;13:2377-2394. doi: 10.2147/IJN.S158536. eCollection 2018.
The development of ideal vaccine adjuvants for intranasal vaccination can provide convenience for many vaccinations. As an ideal intranasal vaccine adjuvant, it should have the properties of assisting soluble antigens to pass the mucosal barrier and potentiating both systemic and mucosal immunity via nasal administration.
By using the advantages of polysaccharides, which can promote both T-helper 1 and 2 responses, curdlan sulfate (CS)--(2-hydroxyl)propyl-3-trimethyl ammonium chitosan chloride (-HTCC) nanoparticles were prepared by interacting CS with -HTCC, and the adjuvancy of the nanoparticles was investigated.
The results showed that the polysaccharide-based nanoparticles induced the proliferation and activation of antigen-presenting cells. High protein-loading efficiency was obtained by testing with the model antigen ovalbumin (Ova), and the Ova adsorbed onto the cationic CS/-HTCC complexes was taken up easily by the epithelium. To evaluate the capacity of the Ova/CS/-HTCC nanoparticles for immune enhancement in vivo, we collected and analyzed immunocytes, serum, and mucosal lavage fluid from intranasally vaccinated mice. The results showed that Ova/CS/-HTCC nanoparticles induced activation and maturation of antigen-presenting cells and provoked the proliferation and differentiation of lymphocytes more significantly compared to the immunization of Ova mixed with aluminum hydroxide gel. Furthermore, CS/-HTCC evoked a significantly higher level of Ova-specific antibodies.
Therefore, these results suggest that CS/-HTCC nanoparticles are ideal vaccine adjuvants for soluble antigens used in intranasal or mucosal vaccination.
开发理想的鼻腔内接种疫苗佐剂可为许多疫苗接种提供便利。作为一种理想的鼻腔内疫苗佐剂,它应该具有辅助可溶性抗原通过黏膜屏障的特性,并通过鼻腔给药增强全身和黏膜免疫。
利用多糖可以促进 Th1 和 Th2 反应的优势,通过 CS 与 -HTCC 相互作用制备硫酸卷曲霉素(CS)-(2-羟丙基)-3-三甲基氯化铵(-HTCC)纳米粒子,并研究了纳米粒子的佐剂作用。
结果表明,基于多糖的纳米粒子诱导了抗原呈递细胞的增殖和激活。通过用模型抗原卵清蛋白(Ova)进行测试,获得了高的蛋白加载效率,并且阳离子 CS/-HTCC 复合物上吸附的 Ova 很容易被上皮细胞摄取。为了评估 Ova/CS/-HTCC 纳米粒子在体内增强免疫的能力,我们从经鼻腔接种的小鼠中收集和分析免疫细胞、血清和黏膜冲洗液。结果表明,与用氢氧化铝凝胶混合免疫 Ova 相比,Ova/CS/-HTCC 纳米粒子诱导抗原呈递细胞的激活和成熟,并更显著地引发淋巴细胞的增殖和分化。此外,CS/-HTCC 引发了更高水平的 Ova 特异性抗体。
因此,这些结果表明 CS/-HTCC 纳米粒子是用于鼻腔内或黏膜内接种的可溶性抗原的理想疫苗佐剂。