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Comprehensive mapping of antigen specific T cell responses in hepatitis C virus infected patients with or without spontaneous viral clearance
Elucidating protective immunity against HCV is important for the development of a preventative vaccine. We hypothesize that spontaneous resolution of acute HCV infection offers clue to protective immune responses, and that DAA therapy affects the quality and quantity of HCV-specific T cell responses...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295680/ https://www.ncbi.nlm.nih.gov/pubmed/28170421 http://dx.doi.org/10.1371/journal.pone.0171217 |
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author | Zhang, Chao Hua, Rui Cui, Yuanyuan Wang, Shasha Yan, Hongqing Li, Dongmei Zhang, Yonghong Tu, Zhengkun Hao, Pei Chen, Xinyue Zhong, Jin Niu, Junqi Jin, Xia |
author_facet | Zhang, Chao Hua, Rui Cui, Yuanyuan Wang, Shasha Yan, Hongqing Li, Dongmei Zhang, Yonghong Tu, Zhengkun Hao, Pei Chen, Xinyue Zhong, Jin Niu, Junqi Jin, Xia |
author_sort | Zhang, Chao |
collection | PubMed |
description | Elucidating protective immunity against HCV is important for the development of a preventative vaccine. We hypothesize that spontaneous resolution of acute HCV infection offers clue to protective immune responses, and that DAA therapy affects the quality and quantity of HCV-specific T cell responses. To test these hypotheses, we performed T cell epitope mapping in 111 HCV-infected individuals including 61 chronically HCV-1b (CHC-1b) infected, 24 chronically HCV-2a (CHC-2a) infected and 26 spontaneously recovered (SPR) patients with 376 overlapping peptides covering the entire HCV polyprotein. Selected T cell epitopes were then used to evaluate T cell responses in another 22 chronically HCV-1b infected patients on DAA therapy. Results showed that SPR had better HCV-specific T cell responses than CHC, as manifested by higher response rate, greater magnitude and broader epitope coverage. In addition, SPR recognized novel epitopes in Core, E1, E2, NS4B, NS5A regions that were not present in the CHC. Furthermore, during the first 24 weeks of DAA therapy, there was no functional immune reconstitution of HCV-specific T cells. These results indicate that T cell responses may be a correlate of protection. Therefore, effective preventative vaccines should elicit a robust T cell response. Although various DAA regimens efficiently cleared viruses from the blood of HCV-infected patients, there was no contemporaneous early T cell immune reconstitution, suggesting that early treatment is needed for preserving the functions of HCV-specific T cells. |
format | Online Article Text |
id | pubmed-5295680 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-52956802017-02-17 Comprehensive mapping of antigen specific T cell responses in hepatitis C virus infected patients with or without spontaneous viral clearance Zhang, Chao Hua, Rui Cui, Yuanyuan Wang, Shasha Yan, Hongqing Li, Dongmei Zhang, Yonghong Tu, Zhengkun Hao, Pei Chen, Xinyue Zhong, Jin Niu, Junqi Jin, Xia PLoS One Research Article Elucidating protective immunity against HCV is important for the development of a preventative vaccine. We hypothesize that spontaneous resolution of acute HCV infection offers clue to protective immune responses, and that DAA therapy affects the quality and quantity of HCV-specific T cell responses. To test these hypotheses, we performed T cell epitope mapping in 111 HCV-infected individuals including 61 chronically HCV-1b (CHC-1b) infected, 24 chronically HCV-2a (CHC-2a) infected and 26 spontaneously recovered (SPR) patients with 376 overlapping peptides covering the entire HCV polyprotein. Selected T cell epitopes were then used to evaluate T cell responses in another 22 chronically HCV-1b infected patients on DAA therapy. Results showed that SPR had better HCV-specific T cell responses than CHC, as manifested by higher response rate, greater magnitude and broader epitope coverage. In addition, SPR recognized novel epitopes in Core, E1, E2, NS4B, NS5A regions that were not present in the CHC. Furthermore, during the first 24 weeks of DAA therapy, there was no functional immune reconstitution of HCV-specific T cells. These results indicate that T cell responses may be a correlate of protection. Therefore, effective preventative vaccines should elicit a robust T cell response. Although various DAA regimens efficiently cleared viruses from the blood of HCV-infected patients, there was no contemporaneous early T cell immune reconstitution, suggesting that early treatment is needed for preserving the functions of HCV-specific T cells. Public Library of Science 2017-02-07 /pmc/articles/PMC5295680/ /pubmed/28170421 http://dx.doi.org/10.1371/journal.pone.0171217 Text en © 2017 Zhang 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Zhang, Chao Hua, Rui Cui, Yuanyuan Wang, Shasha Yan, Hongqing Li, Dongmei Zhang, Yonghong Tu, Zhengkun Hao, Pei Chen, Xinyue Zhong, Jin Niu, Junqi Jin, Xia Comprehensive mapping of antigen specific T cell responses in hepatitis C virus infected patients with or without spontaneous viral clearance |
title | Comprehensive mapping of antigen specific T cell responses in hepatitis C virus infected patients with or without spontaneous viral clearance |
title_full | Comprehensive mapping of antigen specific T cell responses in hepatitis C virus infected patients with or without spontaneous viral clearance |
title_fullStr | Comprehensive mapping of antigen specific T cell responses in hepatitis C virus infected patients with or without spontaneous viral clearance |
title_full_unstemmed | Comprehensive mapping of antigen specific T cell responses in hepatitis C virus infected patients with or without spontaneous viral clearance |
title_short | Comprehensive mapping of antigen specific T cell responses in hepatitis C virus infected patients with or without spontaneous viral clearance |
title_sort | comprehensive mapping of antigen specific t cell responses in hepatitis c virus infected patients with or without spontaneous viral clearance |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295680/ https://www.ncbi.nlm.nih.gov/pubmed/28170421 http://dx.doi.org/10.1371/journal.pone.0171217 |
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