中文摘要：研究利用蛛丝颗粒构建了一种多肽疫苗的传递系统，这种疫苗系统能够产生有效的细胞毒性T细胞反应。研究将重组蛛丝蛋白eADF4(C16)融合到卵清蛋白抗原多肽表面，这种融合既不需要连接体，也不需要组织蛋白酶裂解肽接头。由重组蛋白制备得到的颗粒能够为树突状细胞摄取，这对T细胞反应启动非常关键，从而可以成功激活细胞毒性T细胞，而不需要任何免疫毒性信号或非特异性免疫刺激活性。将这种疫苗皮下免疫小鼠后，蛋白颗粒能够为树突状细胞摄取，并在淋巴结中聚集，从而产生免疫反应。重组蛋白颗粒包含了一个组织蛋白酶裂解接头，即使在没有疫苗佐剂的情况下，也能够在体外诱导产生强烈的细胞毒性T细胞抗原特异性炎性反应。研究阐述了一种基于蛋白的一体化疫苗系统的免疫效率，在整个系统中，蛛丝颗粒作为一种载体整合到多肽抗原中。研究进一步表明，基于重组蛛丝的疫苗非常稳定，加工工艺简单，且易于定制。
外文摘要： The generation of strong T-cell immunity is one of the main challenges for the development of successful vaccines against cancer and major infectious diseases. Here we have engineered spider silk particles as delivery system for a peptide-based vaccination that leads to effective priming of cytotoxic T-cells. The recombinant spider silk protein eADF4(C16) was fused to the antigenic peptide from ovalbumin, either without linker or with a cathepsin cleavable peptide linker. Particles prepared from the hybrid proteins were taken up by dendritic cells, which are essential for T-cell priming, and successfully activated cytotoxic T-cells, without signs of immunotoxicity or unspecific immunostimulatory activity. Upon subcutaneous injection in mice, the particles were taken up by dendritic cells and accumulated in the lymph nodes, where immune responses are generated. Particles from hybrid proteins containing a cathepsin-cleavable linker induced a strong antigen-specific proliferation of cytotoxic T-cells in vivo, even in the absence of a vaccine adjuvant. We thus demonstrate the efficacy of a new vaccine strategy using a protein-based all-in-one vaccination system, where spider silk particles serve as carriers with an incorporated peptide antigen. Our study further suggests that engineered spider silk-based vaccines are extremely stable, easy to manufacture, and readily customizable.
外文关键词：Vaccine delivery, Antigen delivery, Peptide vaccines, Cytotoxic T-cells, Recombinant silk protein
作者：Lucke, M; Mottas, I; Herbst, T; Hotz, C; Romer, L; Schierling, M; Herold, HM; Slotta, U; Spinetti, T; Scheibel, T; Winter, G; Bourquin, C; Engert, J
作者单位：德国慕尼黑大学
期刊名称：BIOMATERIALS
期刊影响因子：8.402
出版年份：2018
出版刊次：7
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