Institute of Immunobiology, Kantonal Hospital St. Gallen, St. Gallen, Switzerland.
mBio. 2010 Sep 14;1(4):e00171-10. doi: 10.1128/mBio.00171-10.
Efficient vaccination against infectious agents and tumors depends on specific antigen targeting to dendritic cells (DCs). We report here that biosafe coronavirus-based vaccine vectors facilitate delivery of multiple antigens and immunostimulatory cytokines to professional antigen-presenting cells in vitro and in vivo. Vaccine vectors based on heavily attenuated murine coronavirus genomes were generated to express epitopes from the lymphocytic choriomeningitis virus glycoprotein, or human Melan-A, in combination with the immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). These vectors selectively targeted DCs in vitro and in vivo resulting in vector-mediated antigen expression and efficient maturation of DCs. Single application of only low vector doses elicited strong and long-lasting cytotoxic T-cell responses, providing protective antiviral and antitumor immunity. Furthermore, human DCs transduced with Melan-A-recombinant human coronavirus 229E efficiently activated tumor-specific CD8(+) T cells. Taken together, this novel vaccine platform is well suited to deliver antigens and immunostimulatory cytokines to DCs and to initiate and maintain protective immunity.
有效的传染病和肿瘤疫苗接种依赖于针对树突状细胞（DC）的特定抗原靶向。我们在此报告称，基于生物安全的冠状病毒疫苗载体可促进多种抗原和免疫刺激性细胞因子向专业抗原呈递细胞的体外和体内传递。基于严重减毒鼠冠状病毒基因组生成了疫苗载体，以表达淋巴细胞性脉络丛脑膜炎病毒糖蛋白或人类黑色素瘤-A 的表位，同时表达免疫刺激性细胞因子粒细胞-巨噬细胞集落刺激因子（GM-CSF）。这些载体在体外和体内选择性地靶向 DC，导致载体介导的抗原表达和 DC 的有效成熟。单次施用低剂量的载体即可引发强烈且持久的细胞毒性 T 细胞反应，提供抗病毒和抗肿瘤的保护免疫。此外，用黑色素瘤-A-重组人 229E 冠状病毒转导的人 DC 可有效激活肿瘤特异性 CD8(+) T 细胞。总之，这种新型疫苗平台非常适合向 DC 传递抗原和免疫刺激性细胞因子，并启动和维持保护性免疫。
