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. 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.
Viral Disease and Vaccine Translational Unit, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
Chao
http://orcid.org/0000-0001-6292-7651
C
Zhang
Department of Hepatology, The First Hospital, Jilin University, Changchun, Jilin, China.
Rui
R
Hua
Department of Hepatology, The First Hospital, Jilin University, Changchun, Jilin, China.
Yuanyuan
Y
Cui
Department of Hepatology, The First Hospital, Jilin University, Changchun, Jilin, China.
Shasha
S
Wang
Department of Hepatology, The First Hospital, Jilin University, Changchun, Jilin, China.
Hongqing
H
Yan
Department of Hepatology, The First Hospital, Jilin University, Changchun, Jilin, China.
Dongmei
D
Li
Department of Hepatology, Beijing You'an Hospital, Capital Medical University, Beijing, China.
Yonghong
Y
Zhang
Institute of Translational Medicine, The First Hospital, Jilin University, Changchun, Jilin, China.
Zhengkun
Z
Tu
Bioinformatics Core, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
Pei
P
Hao
Department of Hepatology, Beijing You'an Hospital, Capital Medical University, Beijing, China.
Xinyue
X
Chen
Viral Hepatitis Unit, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
Jin
J
Zhong
Department of Hepatology, The First Hospital, Jilin University, Changchun, Jilin, China.|Institute of Translational Medicine, The First Hospital, Jilin University, Changchun, Jilin, China.
Junqi
J
Niu
Viral Disease and Vaccine Translational Unit, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
Xia
X
Jin
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000998:Antiviral Agents / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D010455:Peptides / Q000235:genetics / Q000276:immunology; D010802:Phylogeny; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D019562:Viral Load; D055815:Young Adult
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor