Dynamics of interferon-specific gene expression in peripheral blood of interferon alfa-naïve patients with genotype 1 chronic hepatitis C infection treated with albumin-interferon alfa

Vincent G. Bain, Eric M. Yoshida, Kelly D. Kaita, Mark G. Swain, E. Jenny Heathcote, Andy Garcia, Paul A. Moore, Ren Yu, John G. McHutchison, G. Mani Subramanian

Research output: Contribution to journalArticlepeer-review

Abstract

Albumin-interferon alfa (alb-IFN) is a novel recombinant protein derived from IFNα-2b genetically fused to human albumin, which combines in a single polypeptide the antiviral properties of IFNα with the long serum half-life of albumin. Interferon alfa (IFNα) mediated biological responses stem from the engagement of IFNα with its target receptor and subsequent modulation of interferon-specific gene (ISG) expression. The dynamics of ISG expression were evaluated in a Phase 2a study conducted in IFNα naïve patients with genotype 1 chronic hepatitis C (CHC) treated with alb-IFN. Whole blood was obtained pre-dose and on days 7 and 28 from 47 patients enrolled to receive two subcutaneous injections of alb-IFN 14 days apart in five dose cohorts ranging from 200 to1200 μg. Gene expression of nine candidate genes including four ISGs was determined by a TaqMan Real-time PCR assay. There was sustained >5-fold median induction on days 7 and 28 of the ISG's- OAS1, IRF7, IFI44 and IFI27. While all subjects showed a molecular response to alb-IFN, individual variability in pre-treatment gene expression levels and fold of modulation during treatment was observed. At days 7 and 28, induction of OAS1, IFI44 and IRF7 showed significant pair-wise correlation in individual patients (r > 0.7 and P < 0.001). There was no correlation of baseline expression or induction of gene expression with antiviral response. In conclusion, alb-IFN demonstrated robust induction of ISG that was consistent with the molecular response associated with an IFNα.

Original languageEnglish (US)
Pages (from-to)256-262
Number of pages7
JournalHepatology Research
Volume35
Issue number4
DOIs
StatePublished - Aug 1 2006

Keywords

  • Albumin-interferon alfa
  • Interferon-specific gene
  • TaqMan PCR

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases

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