The CD8+ and CD4+ T Cell Immunogen Atlas of Zika Virus Reveals E, NS1 and NS4 Proteins as the Vaccine Targets

寨卡病毒 CD8+ 和 CD4+ T 细胞免疫原图谱显示 E、NS1 和 NS4 蛋白是疫苗靶点

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作者:Hangjie Zhang, Wenling Xiao, Min Zhao, Yingze Zhao, Yongli Zhang, Dan Lu, Shuangshuang Lu, Qingxu Zhang, Weiyu Peng, Liumei Shu, Jie Zhang, Sai Liu, Kexin Zong, Pengyan Wang, Beiwei Ye, Shihua Li, Shuguang Tan, Fuping Zhang, Jianfang Zhou, Peipei Liu, Guizhen Wu, Xuancheng Lu, George F Gao, William

Abstract

Zika virus (ZIKV)-specific T cells are activated by different peptides derived from virus structural and nonstructural proteins, and contributed to the viral clearance or protective immunity. Herein, we have depicted the profile of CD8+ and CD4+ T cell immunogenicity of ZIKV proteins in C57BL/6 (H-2b) and BALB/c (H-2d) mice, and found that featured cellular immunity antigens were variant among different murine alleles. In H-2b mice, the proteins E, NS2, NS3 and NS5 are recognized as immunodominant antigens by CD8+ T cells, while NS4 is dominantly recognized by CD4+ T cells. In contrast, in H-2d mice, NS1 and NS4 are the dominant CD8+ T cell antigen and NS4 as the dominant CD4+ T cell antigen, respectively. Among the synthesized 364 overlapping polypeptides spanning the whole proteome of ZIKV, we mapped 91 and 39 polypeptides which can induce ZIKV-specific T cell responses in H-2b and H-2d mice, respectively. Through the identification of CD8+ T cell epitopes, we found that immunodominant regions E294-302 and NS42351-2360 are hotspots epitopes with a distinct immunodominance hierarchy present in H-2b and H-2d mice, respectively. Our data characterized an overall landscape of the immunogenic spectrum of the ZIKV polyprotein, and provide useful insight into the vaccine development.

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