TY  - JOUR
A1  - Phillips, Sandra
A1  - Mistry, Sameer
A1  - Riva, Antonio
A1  - Cooksley, Helen
A1  - Hadzhiolova-Lebeau, Tanya
A1  - Plavova, Slava
A1  - Katzarov, Krum
A1  - Simonova, Marieta
A1  - Zeuzem, Stefan
A1  - Woffendin, Clive
A1  - Chen, Pei-Jer
A1  - Peng, Cheng-Yuan
A1  - Chang, Ting Tsung
A1  - Lüth, Stefan
A1  - Knegt, Robert Jacobus de
A1  - Choi, Moon Seok
A1  - Wedemeyer, Heiner
A1  - Dao, Michael
A1  - Kim, Chang-Wook
A1  - Chu, Heng-Chen
A1  - Wind-Rotolo, Megan
A1  - Williams, Roger
A1  - Cooney, Elizabeth
A1  - Chokshi, Shilpa
T1  - Peg-Interferon lambda treatment induces robust innate and adaptive immunity in chronic Hepatitis B patients
T2  - Frontiers in immunology
N2  - 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-IFNα treatment for CHB results in a detrimental effect on the functionality of this important antiviral T cell compartment.
KW  - peg-interferon lambda
KW  - direct antiviral
KW  - hepatitis B
KW  - immunity
KW  - in vivo
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/43676
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-436760
SN  - 1664-3224
N1  - Copyright © 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. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
VL  - 8
IS  - Art. 621
SP  - 1
EP  - 13
PB  - Frontiers Media
CY  - Lausanne
ER  -