Ra Jae-Sun, Shin Hyun-Hee, Kang Sebyung, Do Yoonkyung
School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Korea.
Clin Exp Vaccine Res. 2014 Jul;3(2):227-34. doi: 10.7774/cevr.2014.3.2.227. Epub 2014 Jun 20.
Protein cages are promising nanoplatform candidates for efficient delivery systems due to their homogenous size and structure with high biocompatibility and biodegradability. In this study, we investigate the potential of lumazine synthase protein cage as an antigen delivery system to dendritic cells (DCs), which induce antigen-specific T cell proliferation.
Ovalbumin (OVA) peptides OT-1 (SIINFEKL) and OT-2 (ISQAVHAAHAEINEAGR) were genetically inserted to lumazine synthase and each protein cage was over-expressed in Escherichia coli as a soluble protein. The efficiency of antigen delivery and the resulting antigen-specific T cell proliferation by DCs was examined in vitro as well as in vivo.
We successfully generated and characterized OVA peptides carrying lumazine synthase protein cages. The OT-1 and OT-2 peptides carried by lumazine synthases were efficiently delivered and processed by DCs in vitro as well as in vivo, and induced proliferation of OT-1-specific CD8(+)T cells and OT-2-specific CD4(+)T cells.
Our data demonstrate the potential of lumazine synthase protein cage being used as a novel antigen delivery system for DC-based vaccine development in future clinical applications.
蛋白质笼因其尺寸和结构均一,具有高生物相容性和可生物降解性,是高效递送系统中很有前景的纳米平台候选物。在本研究中,我们探究了核黄素合酶蛋白质笼作为抗原递送至树突状细胞(DCs)的潜力,树突状细胞可诱导抗原特异性T细胞增殖。
将卵清蛋白(OVA)肽OT-1(SIINFEKL)和OT-2(ISQAVHAAHAEINEAGR)通过基因工程插入核黄素合酶,每种蛋白质笼在大肠杆菌中作为可溶性蛋白过表达。在体外和体内检测了DCs的抗原递送效率以及由此产生的抗原特异性T细胞增殖情况。
我们成功制备并表征了携带核黄素合酶蛋白质笼的OVA肽。核黄素合酶携带的OT-1和OT-2肽在体外和体内均能被DCs有效递送和加工,并诱导OT-1特异性CD8(+)T细胞和OT-2特异性CD4(+)T细胞增殖。
我们的数据证明了核黄素合酶蛋白质笼在未来临床应用中作为基于DC的疫苗开发的新型抗原递送系统的潜力。