中文摘要
经皮免疫相比于注射途径,是顺应性好、更安全高效的新型疫苗接种方法和递送系统。然而由于皮肤角质层的天然屏障作用,如何使大分子抗原有效透过角质层,同时被APCs识别摄取诱发免疫应答是经皮免疫亟待解决的关键问题。纳米递药系统在促进透皮和疫苗递送方面有着巨大的潜力。因此,本项目拟以OVA为模型抗原,基于MF59的o/w型纳米乳为抗原载体,充分发挥纳米乳促进透皮和免疫佐剂优势,并对纳米乳表面进行DEC 205分子的scFv修饰,构建特异性靶向皮肤APCs的免疫纳米乳,借助多功能纳米乳疫苗递送系统,实现经皮免疫。以新型团聚淬灭效应(ACQ)探针为研究工具,对纳米乳载体进行标记,验证基于纳米乳整体被APCs识别摄取的免疫机制;比较纳米载体、免疫佐剂、纳米乳表面修饰的抗体在经皮免疫中的作用,深入阐明其免疫应答的机制。这对于经皮免疫的发展以及临床应用具有重要的价值。
英文摘要
Transcutaneous immunization is a better, safer and more efficient new vaccination delivery system than the injection route. However, due to the natural barrier effect of the skin stratum corneum, how to delivery the macromolecular antigen effectively through the stratum corneum and identified by the skin antigen-presenting cells to induce immune response is a key issue to transcutaneous immunization. Nanoparticles drug delivery systems have great potential in promoting transdermal and vaccine delivery. Therefore, this project intends to choose OVA as model antigen, MF59-based o/w nanoemulsion as antigen carriers, take full advantages of nanoemulsion to promoting transdermal delivery and acting as immune adjuvant, besides, constructed an active targeting immune nanoemulsion to skin APCs by modified the surface of nanoemulsion with DEC 205 scFv, to achieve effective transcutaneous immunization. The new ACQ probe is chosen as the research tool, with ACQ probe as marker of nanoemulsion carriers, to explore the immune mechanism based on the uptake of integral nanocarriers by APCs. Besides, clarified its immune response mechanism by comparing the contribution of the nanocarrier, immune adjuvant, and nanoemulsion surface modification in transcutaneous immunization. Which has great value for the development of transcutaneous immunization and its clinical application.
