基于HLA-A、-B和-C等位基因分布推断中国登革病毒四种血清型分离株NS5蛋白的保护性CD8+ T细胞表位：对基于表位的通用疫苗设计的启示
Inferring Protective CD8+ T-Cell Epitopes for NS5 Protein of Four Serotypes of Dengue Virus Chinese Isolates Based on HLA-A, -B and -C Allelic Distribution: Implications for Epitope-Based Universal Vaccine Design.
作者信息
Shi Jiandong, Sun Jing, Wu Meini, Hu Ningzhu, Li Jianfan, Li Yanhan, Wang Haixuan, Hu Yunzhang
机构信息
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, 650118, China; Yunnan Provincial Key Laboratory of Arbo Infectious Disease Control Research (Preparing), Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, 650118, China.
出版信息
PLoS One. 2015 Sep 18;10(9):e0138729. doi: 10.1371/journal.pone.0138729. eCollection 2015.
Dengue is one of the most globally serious vector-borne infectious diseases in tropical and subtropical areas for which there are currently no effective vaccines. The most highly conserved flavivirus protein, NS5, is an indispensable target of CD8+ T-cells, making it an ideal vaccine design target. Using the Immune Epitope Database (IEDB), CD8+ T-cell epitopes of the dengue virus (DENV) NS5 protein were predicted by genotypic frequency of the HLA-A,-B, and-C alleles in Chinese population. Antigenicity scores of all predicted epitopes were analyzed using VaxiJen v2.0. The IEDB analysis revealed that 116 antigenic epitopes for HLA-A (21),-B (53), and-C (42) had high affinity for HLA molecules. Of them, 14 had 90.97-99.35% conversancy among the four serotypes. Moreover, five candidate epitopes, including 200NS5210 (94.84%, A11:01), 515NS5525 (98.71%, A24:02), 225NS5232 (99.35%, A33:03), 516NS5523 (98.71%, A33:03), and 284NS5291 (98.06%, A33:03), were presented by HLA-A. Four candidate epitopes, including 234NS5241 (96.77%, B13:01), 92NS599 (98.06%, B15:01, B15:02, and B46:01), 262NS5269 (92.90%, B38:02), and 538NS5547 (90.97%, B51:01), were presented by HLA-B. Another 9 candidate epitopes, including 514NS5522 (98.71%, C01:02), 514NS5524 (98.71%, C01:02 and C14:02), 92NS599 (98.06%, C03:02 and C15:02), 362NS5369 (44.84%, C03:04 and C08:01), 225NS5232 (99.35%, C04:01), 234NS5241(96.77%, C04:01), 361NS5369 (94.84%, C04:01), 515NS5522 (98.71%, C14:02), 515NS5524 (98.71%, C14:02), were presented by HLA-C. Further data showed that the four-epitope combination of 92NS599 (B15:01, B15:02, B46:01, C03:02 and C15:02), 200NS5210 (A11:01), 362NS5369 (C03:04, C08:01), and 514NS5524 (C01:02, C*14:02) could vaccinate >90% of individuals in China. Further in vivo study of our inferred novel epitopes will be needed for a T-cell epitope-based universal vaccine development that may prevent all four China-endemic DENV serotypes.
登革热是热带和亚热带地区全球最严重的媒介传播传染病之一，目前尚无有效的疫苗。黄病毒中最保守的蛋白NS5是CD8 + T细胞不可或缺的靶点，使其成为理想的疫苗设计靶点。利用免疫表位数据库（IEDB），通过中国人群中HLA - A、-B和 - C等位基因的基因型频率预测登革病毒（DENV）NS5蛋白的CD8 + T细胞表位。使用VaxiJen v2.0分析所有预测表位的抗原性评分。IEDB分析显示，针对HLA - A（21个）、-B（53个）和 - C（42个）的116个抗原表位对HLA分子具有高亲和力。其中，14个在四种血清型中的保守性为90.97 - 99.35%。此外，HLA - A呈现了五个候选表位，包括200NS5210（94.84%，A11:01）、515NS5525（98.71%，A24:02）、225NS5232（99.35%，A33:03）、516NS5523（98.71%，A33:03）和284NS5291（98.06%，A33:03）。HLA - B呈现了四个候选表位，包括234NS5241（96.77%，B13:01）、92NS599（98.06%，B15:01、B15:02和B46:01）、262NS5269（92.90%，B38:02）和538NS5547（90.97%）。HLA - C呈现了另外9个候选表位，包括514NS5522（98.71%，C01:02）、514NS5524（98.71%，C01:02和C14:02）、92NS599（98.06%，C03:02和C15:02）、362NS5369（44.84%，C03:04和C08:01）、225NS5232（99.35%，C04:01）、234NS5241（96.77%，C04:01）、361NS5369（94.84%，C04:01）、515NS5522（98.71%，C14:02）、515NS5524（98.71%，C14:02）。进一步的数据显示，92NS599（B15:01、B15:02、B46:01、C03:02和C15:02）、200NS5210（A11:01）、362NS5369（C03:04、C08:01）和514NS5524（C01:02、C14:02）的四表位组合可使中国超过90%的个体接种疫苗。为了开发基于T细胞表位的通用疫苗以预防所有四种在中国流行的DENV血清型，需要对我们推断的新型表位进行进一步的体内研究。
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