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

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.