Peg-Interferon lambda treatment induces robust innate and adaptive immunity in chronic Hepatitis B patients

  • 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.

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Author:Sandra Phillips, Sameer Mistry, Antonio Riva, Helen Cooksley, Tanya Hadzhiolova-Lebeau, Slava Plavova, Krum Katzarov, Marieta Simonova, Stefan ZeuzemORCiDGND, Clive Woffendin, Pei-Jer Chen, Cheng-Yuan Peng, Ting Tsung Chang, Stefan Lüth, Robert Jacobus de Knegt, Moon Seok Choi, Heiner WedemeyerORCiDGND, Michael Dao, Chang-Wook Kim, Heng-Chen Chu, Megan Wind-Rotolo, Roger Williams, Elizabeth Cooney, Shilpa Chokshi
URN:urn:nbn:de:hebis:30:3-436760
DOI:https://doi.org/10.3389/fimmu.2017.00621
ISSN:1664-3224
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/28611778
Parent Title (English):Frontiers in immunology
Publisher:Frontiers Media
Place of publication:Lausanne
Contributor(s):Marco A. Cassatella
Document Type:Article
Language:English
Date of Publication (online):2017/06/26
Date of first Publication:2017/05/29
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2017/06/26
Tag:direct antiviral; hepatitis B; immunity; in vivo; peg-interferon lambda
Volume:8
Issue:Art. 621
Page Number:13
First Page:1
Last Page:13
Note:
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.
HeBIS-PPN:424953056
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0