Qiu Yuqin, Guo Lei, Zhang Suohui, Xu Bai, Gao Yunhua, Hu Yan, Hou Jun, Bai Bingke, Shen Honghui, Mao Panyong
a Key Laboratory of Photochemical Conversion and Optoelectronic Materials , Technical Institute of Physics and Chemistry, Chinese Academy of Sciences , Haidian , Beijing , China , and.
b 302 Military Hospital of China , Fengtai , Beijing , China.
Drug Deliv. 2016 Sep;23(7):2391-2398. doi: 10.3109/10717544.2014.992497. Epub 2015 Jan 27.
DNA vaccines are simple to produce and can generate strong cellular and humoral immune response, making them attractive vaccine candidates. However, a major shortcoming of DNA vaccines is their poor immunogenicity when administered intramuscularly. Transcutaneous immunization (TCI) via microneedles is a promising alternative delivery route to enhance the vaccination efficacy. A novel dissolving microneedle array (DMA)-based TCI system loaded with cationic liposomes encapsulated with hepatitis B DNA vaccine and adjuvant CpG ODN was developed and characterized. The pGFP expression in mouse skin using DMA was imaged over time. In vivo immunity tests in mice were performed to observe the capability of DMA to induce immune response after delivery of DNA. The results showed that pGFP could be delivered into skin by DMA and expressed in skin. Further, the amount of expressed GFP was likely to peak at day 4. The immunity tests showed that the DMA-based DNA vaccination could induce effective immune response. CpG ODN significantly improved the immune response and achieved the shift of immune type from predominate Th2 type to a balance Th1/Th2 type. The cationic liposomes could further improve the immunogenicity of DNA vaccine. In conclusion, the novel DMA-based TCI system can effectively deliver hepatitis B DNA vaccine into skin, inducing effective immune response and change the immune type by adjuvant CpG ODN.
DNA疫苗易于生产，可产生强烈的细胞免疫和体液免疫反应，使其成为有吸引力的候选疫苗。然而，DNA疫苗的一个主要缺点是肌内注射时免疫原性较差。通过微针进行经皮免疫（TCI）是一种有前景的替代给药途径，可提高疫苗接种效果。开发并表征了一种基于新型溶解微针阵列（DMA）的TCI系统，该系统装载有包裹乙型肝炎DNA疫苗和佐剂CpG ODN的阳离子脂质体。使用DMA对小鼠皮肤中的pGFP表达随时间进行成像。在小鼠中进行体内免疫测试，以观察DMA在递送DNA后诱导免疫反应的能力。结果表明，pGFP可通过DMA递送至皮肤并在皮肤中表达。此外，GFP表达量可能在第4天达到峰值。免疫测试表明，基于DMA的DNA疫苗接种可诱导有效的免疫反应。CpG ODN显著改善了免疫反应，并实现了免疫类型从主要的Th2型向Th1/Th2平衡型的转变。阳离子脂质体可进一步提高DNA疫苗的免疫原性。总之，新型基于DMA的TCI系统可有效地将乙型肝炎DNA疫苗递送至皮肤，诱导有效的免疫反应，并通过佐剂CpG ODN改变免疫类型。
