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...

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Autores principales: Shi, Jiandong, Sun, Jing, Wu, Meini, Hu, Ningzhu, Li, Jianfan, Li, Yanhan, Wang, Haixuan, Hu, Yunzhang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575106/
https://www.ncbi.nlm.nih.gov/pubmed/26381649
http://dx.doi.org/10.1371/journal.pone.0138729
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author Shi, Jiandong
Sun, Jing
Wu, Meini
Hu, Ningzhu
Li, Jianfan
Li, Yanhan
Wang, Haixuan
Hu, Yunzhang
author_facet Shi, Jiandong
Sun, Jing
Wu, Meini
Hu, Ningzhu
Li, Jianfan
Li, Yanhan
Wang, Haixuan
Hu, Yunzhang
author_sort Shi, Jiandong
collection PubMed
description 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.
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spelling pubmed-45751062015-09-25 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 Shi, Jiandong Sun, Jing Wu, Meini Hu, Ningzhu Li, Jianfan Li, Yanhan Wang, Haixuan Hu, Yunzhang PLoS One Research Article 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. Public Library of Science 2015-09-18 /pmc/articles/PMC4575106/ /pubmed/26381649 http://dx.doi.org/10.1371/journal.pone.0138729 Text en © 2015 Shi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Shi, Jiandong
Sun, Jing
Wu, Meini
Hu, Ningzhu
Li, Jianfan
Li, Yanhan
Wang, Haixuan
Hu, Yunzhang
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
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575106/
https://www.ncbi.nlm.nih.gov/pubmed/26381649
http://dx.doi.org/10.1371/journal.pone.0138729
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