Luo Li, Qin Tao, Huang Yifan, Zheng Sisi, Bo Ruonan, Liu Zhenguang, Xing Jie, Hu Yuanliang, Liu Jiaguo, Wang Deyun
a College of Veterinary Medicine , Nanjing Agricultural University , Nanjing , PR China.
b Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal , Fujian Agriculture and Forestry University , Fuzhou , PR China.
Drug Deliv. 2017 Nov;24(1):1099-1111. doi: 10.1080/10717544.2017.1359861.
Biocompatible and biodegradable poly(lactic-co-glycolic acid) (PLGA) has been approved by the US Food and Drug Administration and has frequently been used to develop potential vaccine delivery systems. The immunoregulation and immunopotentiation of Chinese yam polysaccharide (CYP) have been widely demonstrated. In the current study, cell uptake mechanisms in dendritic cells (DCs) were monitored in vitro using confocal laser scanning microscopy, transmission electron microscopy, and flow cytometry. To study a CYP-PLGA nanoparticle-adjuvanted delivery system, CYP and ovalbumin (OVA) were encapsulated in PLGA nanoparticles (CYPPs) to act as a vaccine, and the formulation was tested in immunized mice. The CYPPs more easily underwent uptake by DCs in vitro, and CYPP/OVA could stimulate more effective antigen-specific immune responses than any of the single-component formulations in vivo. Mice immunized using CYPP/OVA exhibited more secretion of OVA-specific IgG antibodies, better proliferation, and higher cytokine secretion by splenocytes and significant activation of CD3CD4 and CD3CD8 T cells. Overall, the CYPP/OVA formulation produced a stronger humoral and cellular immune response and a mixed Th1/Th2 immune response with a greater Th1 bias in comparison with the other formulations. In conclusion, the data demonstrate that the CYPP-adjuvanted delivery system has the potential to strengthen immune responses and lay the foundation for novel adjuvant design.
生物相容性和可生物降解的聚乳酸-乙醇酸共聚物(PLGA)已获得美国食品药品监督管理局的批准,并经常用于开发潜在的疫苗递送系统。山药多糖(CYP)的免疫调节和免疫增强作用已得到广泛证实。在本研究中,使用共聚焦激光扫描显微镜、透射电子显微镜和流式细胞术在体外监测树突状细胞(DCs)中的细胞摄取机制。为了研究CYP-PLGA纳米颗粒佐剂递送系统,将CYP和卵清蛋白(OVA)包裹在PLGA纳米颗粒(CYPPs)中作为疫苗,并在免疫小鼠中对该制剂进行测试。CYPPs在体外更容易被DCs摄取,并且CYPP/OVA在体内比任何单一组分制剂都能刺激更有效的抗原特异性免疫反应。用CYPP/OVA免疫的小鼠表现出更多的OVA特异性IgG抗体分泌、更好的增殖以及脾细胞更高的细胞因子分泌,并且CD3CD4和CD3CD8 T细胞有显著激活。总体而言,与其他制剂相比,CYPP/OVA制剂产生了更强的体液和细胞免疫反应以及混合的Th1/Th2免疫反应,且Th1偏向更大。总之,数据表明CYPP佐剂递送系统有增强免疫反应的潜力,并为新型佐剂设计奠定了基础。