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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.
The efficacy of antiviral treatment for chronic hepatitis C virus (HCV) infection is determined by measuring HCV RNA at specific time points throughout therapy using highly sensitive and accurate HCV RNA assays. This study compared the performances of two recently developed real-time PCR HCV RNA assays, cobas HCV for use on the cobas 6800/8800 systems (cobas 6800/8800 HCV) and cobas HCV for use on the cobas 4800 system (cobas 4800 HCV), with those of two established assays, the Cobas AmpliPrep/Cobas TaqMan HCV quantitative test, version 2 (CAP/CTM v2) and the Cobas TaqMan HCV test, version 2 for use with the High Pure system (HPS/CTM v2). The limits of detection (LODs) and linearity at lower concentrations (5 to 1000 IU/ml) were assessed for cobas 6800/8800 HCV and cobas 4800 HCV using WHO standard traceable panels representing HCV genotypes (GT) 1 to 4. Pairwise assay comparisons were also performed using 245 clinical samples representing HCV GT 1 to GT 4. Results from cobas 6800/8800 HCV and cobas 4800 HCV were linear at low HCV RNA concentrations (<0.3 log10 IU/ml difference between expected and observed results) with LODs of 8.2 IU/ml and 11.7 IU/ml, respectively, for GT 1. The new assays showed excellent agreement with results from CAP/CTM v2 and HPS/CTM v2 in samples with quantifiable viral loads. The concordances using the 6 million IU/ml cutoff were high among all four assays (90 to 94%). In conclusion, the cobas 6800/8800 HCV and cobas 4800 HCV tests are sensitive and linear and correlate well with the established Roche assays used in clinical practice.