Peg-interferon lambda treatment induces robust innate and adaptive immunity in chronic hepatitis B patients
Journal
Frontiers in Immunology
Journal Volume
8
Journal Issue
MAY
Pages
621
Date Issued
2017
Author(s)
Phillips S.
Mistry S.
Riva A.
Cooksley H.
Hadzhiolova-Lebeau T.
Plavova S.
Katzarov K.
Simonova M.
Zeuzem S.
Woffendin C.
Peng C.-Y.
Chang T.-T.
Lueth S.
Knegt R.D.
Choi M.-S.
Wedemeyer H.
Dao M.
Kim C.-W.
Chu H.-C.
Wind-Rotolo M.
Williams R.
Cooney E.
Chokshi S.
Abstract
IFN-lambda (IFNλ) is a member of the type III IFN family and is reported to possess anti-pathogen, anti-cancer, and immunomodulatory properties; however, there are limited data regarding its impact on host immune responses in vivo. We performed longitudinal and comprehensive immunosurveillance to assess the ability of pegylated (peg)-IFNλ to augment antiviral host immunity as part of a clinical trial assessing the efficacy of peg-IFNλ in chronic hepatitis B (CHB) patients. These patients were pretreated with directly acting antiviral therapy (entecavir) for 12 weeks with subsequent addition of peg-IFNλ for up to 32 weeks. In a subgroup of patients, the addition of peg-IFNλ provoked high serum levels of antiviral cytokine IL-18. We also observed the enhancement of natural killer cell polyfunctionality and the recovery of a pan-genotypic HBV-specific CD4+ T cells producing IFN-γ with maintenance of HBV-specific CD8+ T cell antiviral and cytotoxic activities. It was only in these patients that we observed strong virological control with reductions in both viral replication and HBV antigen levels. Here, we show for the first time that in vivo peg-IFNλ displays significant immunostimulatory properties with improvements in the main effectors mediating anti-HBV immunity. Interestingly, the maintenance in HBV-specific CD8+ T cells in the presence of peg-IFNλ is in contrast to previous studies showing that peg-IFNa treatment for CHB results in a detrimental effect on the functionality of this important antiviral T cell compartment. ? 2017 Phillips, Mistry, Riva, Cooksley, Hadzhiolova-Lebeau, Plavova, Katzarov, Simonova, Zeuzem, Woffendin, Chen, Peng, Chang, Lueth, De Knegt, Choi, Wedemeyer, Dao, Kim, Chu, Wind-Rotolo, Williams, Cooney and Chokshi.
Subjects
Direct antiviral; Hepatitis B; Immunity; In vivo; Peg-interferon lambda
SDGs
Other Subjects
alpha1 interferon; CD16 antigen; CD56 antigen; entecavir; gamma interferon; granzyme B; hepatitis B surface antigen; interleukin 10; interleukin 12; interleukin 12p70; interleukin 15; interleukin 17; interleukin 18; interleukin 2; interleukin 6; interleukin 8; macrophage inflammatory protein 1alpha; peginterferon lambda; tumor necrosis factor; tumor necrosis factor related apoptosis inducing ligand; adaptive immunity; adult; alanine aminotransferase blood level; analysis of variance; Article; cell differentiation assay; chronic hepatitis B; clinical article; controlled study; degranulation assay; enzyme linked immunospot assay; female; flow cytometry; fluorescence activated cell sorting; human; immune response; immunosurveillance; innate immunity; male; middle aged; natural killer cell; peripheral blood mononuclear cell; signal transduction; virus replication
Publisher
Frontiers Media S.A.
Type
journal article