title: 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 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%, 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 four-epitope 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.
authors.affiliation: 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.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Meini
authors.initials: M
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Ningzhu
authors.initials: N
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Jianfan
authors.initials: J
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Yanhan
authors.initials: Y
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Haixuan
authors.initials: H
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Yunzhang
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000483:Alleles; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002681:China; D003715:Dengue / Q000276:immunology / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000276:immunology*; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D017361:Viral Nonstructural Proteins
chemical_list: D000956:Antigens, Viral; D053059:Dengue Vaccines; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; C582223:NS5 protein, dengue virus; D017361:Viral Nonstructural Proteins