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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  200 NS5 210  (94.84%, A*11:01),  515 NS5 525  (98.71%, A*24:02),  225 NS5 232  (99.35%, A*33:03),  516 NS5 523  (98.71%, A*33:03), and  284 NS5 291  (98.06%, A*33:03), were presented by HLA-A. Four candidate epitopes, including  234 NS5 241  (96.77%, B*13:01),  92 NS5 99  (98.06%, B*15:01, B*15:02, and B*46:01),  262 NS5 269  (92.90%, B*38:02), and  538 NS5 547  (90.97%, B*51:01), were presented by HLA-B. Another 9 candidate epitopes, including  514 NS5 522  (98.71%, C*01:02),  514 NS5 524  (98.71%, C*01:02 and C*14:02),  92 NS5 99  (98.06%, C*03:02 and C*15:02),  362 NS5 369  (44.84%, C*03:04 and C*08:01),  225 NS5 232  (99.35%, C*04:01),  234 NS5 241 (96.77%, C*04:01),  361 NS5 369  (94.84%, C*04:01),  515 NS5 522  (98.71%, C*14:02),  515 NS5 524  (98.71%, C*14:02), were presented by HLA-C. Further data showed that the four-epitope combination of  92 NS5 99  (B*15:01, B*15:02, B*46:01, C*03:02 and C*15:02),  200 NS5 210  (A*11:01),  362 NS5 369  (C*03:04, C*08:01), and  514 NS5 524  (C*01:02, 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.

plos one

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