Epitopes described in "Successful vaccination induces multifunctional memory T-cell precursors associated with early control of hepatitis C virus."

Article Authors:Su-Hyung Park; Eui-Cheol Shin; Stefania Capone; Laura Caggiari; Valli De Re; Alfredo Nicosia; Antonella Folgori; Barbara Rehermann
Article Title:Successful vaccination induces multifunctional memory T-cell precursors associated with early control of hepatitis C virus.
Reference Detail
Reference ID:1025992
Abstract:BACKGROUND & AIMS: T cells are an important component for development of a vaccine against hepatitis C virus (HCV), but little is known about the features of successful vaccine-induced T cells. METHODS: We compared the phenotype, function, and kinetics of vaccine-induced and infection-induced T cells in chimpanzees with HCV infection using multicolor flow cytometry and real-time polymerase chain reaction. RESULTS: In chimpanzees successfully vaccinated with recombinant adenovirus and DNA against HCV NS3-5, HCV-specific T cells appeared earlier, maintained better functionality, and persisted at higher frequencies for a longer time after HCV challenge, than those of mock-vaccinated chimpanzees. Vaccine-induced T cells displayed higher levels of CD127, a marker of memory precursors, and lower levels of programmed death-1 (PD-1) than infection-induced T cells. Vaccine-induced, but not infection-induced, T cells were multifunctional; their ability to secrete interferon gamma and tumor necrosis factor correlated with early expression of CD127 but not PD-1. Based on a comparison of vaccine-induced and infection-induced T cells from the same chimpanzee, the CD127(+) memory precursor phenotype was induced by the vaccine itself rather than by low viremia. In contrast, induction of PD-1 correlated with viremia, and levels of intrahepatic PD-1, PD-L1, and 2,5-OAS-1 messenger RNAs correlated with peak titers of HCV. CONCLUSIONS: Compared with infection, vaccination-induced HCV-specific CD127(+) T cells with high functionality that persisted at higher levels for a longer time. Control of viremia prevented up-regulation of PD-1 on T cells and induction of PD-1, PD-L1, and 2,5-OAS-1 in the liver. Early development of a memory T-cell phenotype and, via control of viremia, attenuation of the inhibitory PD1-PD-L1 pathway might be necessary components of successful vaccine-induced protection against HCV.
Affiliations:Immunology Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA.
Reference Type:Literature
PubMed ID:22705008
Journal Volume:143
Article Pages:1048-60.e4
Journal ISSN:0016-5085
Article Chemical List:Antigens, CD274;DNA, Viral;Interleukin-7 Receptor alpha Subunit;Programmed Cell Death 1 Receptor;RNA, Messenger;Tumor Necrosis Factor-alpha;Viral Hepatitis Vaccines;Interferon-gamma;2',5'-Oligoadenylate Synthetase
Article MeSH List:2',5'-Oligoadenylate Synthetase(genetics); Analysis of Variance; Animals; Antigens, CD274(genetics); CD8-Positive T-Lymphocytes(drug effects; metabolism); DNA, Viral(immunology); Hepacivirus(immunology); Hepatitis C(immunology; metabolism); Immunologic Memory; Interferon-gamma(metabolism); Interleukin-7 Receptor alpha Subunit(metabolism); Liver(metabolism); Mice; Mice, Inbred C57BL; Pan troglodytes; Phenotype; Precursor Cells, T-Lymphoid(drug effects; metabolism); Programmed Cell Death 1 Receptor(genetics; metabolism); RNA, Messenger(metabolism); Statistics, Nonparametric; Tumor Necrosis Factor-alpha(metabolism); Vaccination; Viral Hepatitis Vaccines(immunology; pharmacology); Viral Load
Curation Last Updated:2015-06-07 20:26:19