PASylated interferon α efficiently suppresses hepatitis B virus and induces anti-HBs seroconversion in HBV-transgenic mice

Antiviral Res. 2019 Jan;161:134-143. doi: 10.1016/j.antiviral.2018.11.003. Epub 2018 Nov 12.


Interferon α (IFNα) so far is the only therapeutic option for chronic hepatitis B virus (HBV) infection that can lead to virus clearance. Unfortunately, its application is limited by side effects and response rates are low. The aim of this study was to generate a novel long-acting IFNα with the help of PASylation technology that adds a polypeptide comprising Proline, Alanine and Serine (PAS) to increase plasma half-life. Following evaluation of four selected recombinant murine IFNα (mIFNα) subtypes in cell culture, the most active subtype, mIFNα11, was fused with a 600 amino acid PAS chain. The activity of PAS-mIFNα was assessed by interferon bioassay and further evaluated for induction of interferon-stimulated genes (ISG) and antiviral efficacy in cell culture as well as in HBV-transgenic mice. PAS-mIFNα induced expression of ISG comparable to unmodified mIFNα and, likewise, evoked dose-dependent reduction of HBV replication in vitro. In vivo, PAS-mIFNα led to pronounced suppression of HBV replication without detectable liver damage whereas conventional mIFNα treatment only had a modest antiviral effect. Importantly, all PAS-mIFNα treated mice showed an anti-HBs antibody response, lost HBsAg and achieved seroconversion after three weeks. PASylated IFNα showed a profoundly increased antiviral effect in vivo compared to the non-modified version without toxicity, providing proof-of-concept that an improved IFNα can achieve higher rates of HBV antiviral and immune control.

Keywords: HBV transgenic mouse; Interferon alpha; PASylation; Plasma half-life; Seroconversion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / therapeutic use*
  • Half-Life
  • Hepatitis B Antibodies / blood
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / physiology
  • Hepatitis B, Chronic / drug therapy*
  • Interferon-alpha / blood
  • Interferon-alpha / therapeutic use*
  • Mice
  • Mice, Transgenic
  • Peptides / therapeutic use
  • Proof of Concept Study
  • Seroconversion*
  • Virus Replication / drug effects*


  • Antiviral Agents
  • Hepatitis B Antibodies
  • Interferon-alpha
  • Peptides