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

Abstract

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 HLAA,-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 HLAmolecules. Of them, 14 had 90.97-99.35% conversancy among the four serotypes. Moreover, five candidate epitopes, including 200NS5210 (94.84%, A∗11:01), 515NS5525 (98.71%, A∗24:02), 225NS5232 (99.35%, A∗33:03), 516NS5523 (98.71%, A∗33:03), and 284NS5291 (98.06%, A∗33:03), were presented by HLA-A. Four candidate epitopes, including 234NS5241 (96.77%, B∗13:01), 92NS599 (98.06%, B∗15:01, B∗15:02, and B∗46:01), 262NS5269 (92.90%, B∗38:02), and 538NS5547 (90.97%, B∗51:01), were presented by HLA-B. Another 9 candidate epitopes, including 514NS5522 (98.71%, C∗01:02), 514NS5524 (98.71%, C∗01:02 and C∗14:02), 92NS599 (98.06%, C∗03:02 and C∗15:02), 362NS5369 (44.84%, C∗03:04 and C∗08:01), 225NS5232 (99.35%, C∗04:01), 234NS5241(96.77%, C∗04:01), 361NS5369 (94.84%, C∗04:01), 515NS5522 (98.71%, C∗14:02), 515NS5524 (98.71%, C∗14:02), were presented by HLA-C. Further data showed that the fourepitope combination of 92NS599 (B∗15:01, B∗15:02, B∗46:01, C∗03:02 and C∗15:02), 200NS5210 (A∗11:01), 362NS5369 (C∗03:04, C∗08:01), and 514NS5524 (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.