College of Marine Life Science, Ocean University of China, 5# Yushan Road, Qingdao 266003, Shandong Province, China.
J Mater Chem B. 2019 Aug 7;7(31):4854-4866. doi: 10.1039/c9tb00448c.
The efficient delivery of vaccines to draining lymph nodes and the induction of robust local immune responses are crucial for immunotherapy. Transdermal administration has been evidenced to facilitate the delivery of ingredients to lymph nodes. In this study, transfersomes with opposite surface charges were applied for antigen encapsulation and these were integrated with dissolving microneedles to investigate their effects on immune responses via transdermal immunization. The microneedles were easily inserted into mouse skin and achieved the local release of nanovaccines into the dermis through dissolution. Although anionic nanovaccines promoted cellular uptake via DC2.4, cationic nanovaccines exhibited stronger escape capacities from endocytic compartments, facilitating antigen processing via an MHC-I presentation pathway, and formed larger accumulations in lymph nodes. Compared with their anionic counterparts, the cationic nanovaccines more efficiently activated DC maturation and induced Th1 immunity; this was suggested by the significantly increased IgG2a/IgG1 ratio and elevated cytokine secretion from Th1 cells, without an enhancement in the Th2 response. Such an enhanced Th1 antigen-specific immune response in lymph nodes via a transdermal vaccine delivery platform is beneficial for potential immunotherapy approaches.
高效地将疫苗递送至引流淋巴结并诱导强烈的局部免疫反应对于免疫治疗至关重要。经皮给药已被证明有助于将成分递送至淋巴结。在这项研究中，采用具有相反表面电荷的传递体来包封抗原，并将其与溶解型微针结合，通过经皮免疫来研究它们对免疫反应的影响。微针很容易插入到小鼠皮肤中，并通过溶解在真皮中实现纳米疫苗的局部释放。尽管阴离子纳米疫苗通过 DC2.4 促进细胞摄取，但阳离子纳米疫苗表现出更强的从内吞隔室逃逸的能力，通过 MHC-I 呈递途径促进抗原加工，并在淋巴结中形成更大的聚集。与阴离子纳米疫苗相比，阳离子纳米疫苗更有效地激活 DC 成熟并诱导 Th1 免疫；这是通过 Th1 细胞中 IgG2a/IgG1 比值的显著增加和细胞因子的分泌增加来证明的，而 Th2 反应没有增强。通过经皮疫苗传递平台在淋巴结中增强的 Th1 抗原特异性免疫反应有利于潜在的免疫治疗方法。
