The bovine IFN-ω (BoIFN-ω) multigene family is located on chromosome 8, which has 14 potential functional genes and 10 pseudogenes. After aligning 14 BoIFN-ω subtypes and assigning the most frequently occurring amino acids in each position, one artificial consensus BoIFN-ω (CoBoIFN-ω) gene was designed, optimized and synthesized. Then, CoBoIFN-ω was expressed in Pichia pastoris, which was demonstrated to have 3.94-fold and 14.3-fold higher antiviral activity against VSV on MDBK cells than that of BoIFN-ω24 and BoIFN-ω3, respectively. Besides this, CoBoIFN-ω was confirmed to have antiviral activity against VSV on BL, BT, PK-15 cells, and against BEV, BHV-1, BPIV3 on MDBK cells. Additionally, CoBoIFN-ω could bind with bovine type I IFN receptors, and then activate the promoters of NF-κB, ISRE and BoIFN-β, and induce the transcription of ISGs and expression of Mx1 and NF-κB p65, which suggested CoBoIFN-ω exerts antiviral activity via activation of the JAK-STAT signaling pathway. Overall, this research on CoBoIFN-ω not only extends and improves consensus IFN research, but also reveals that CoBoIFN-ω has the potential to be used in the therapy of bovine viral diseases.

BACKGROUND: Studies of the retreatment with consensus interferon (CIFN) and ribavirin (RBV) of hepatitis C virus (HCV)-infected patients who failed prior pegylated interferon alfa/ribavirin (PEG-IFN/RBV) have found quite variable efficacy and tolerability of this therapy. As such, CIFN/RBV use and efficacy in clinical practice were evaluated within the Department of Veterans Affairs (VA), the largest national, integrated system for HCV care.
OBJECTIVE: The purpose of this study was to determine rates of sustained virologic response (SVR) and patterns of CIFN/RBV use in the VA. Methods included retrospective review of national VA data in HCV-infected patients who had previously failed≥12 weeks of PEG-IFN/RBV and were prescribed CIFN/RBV between October 1, 2003 and September 30, 2006.
RESULTS: A total of 597 patients met the study criteria. CIFN was primarily dosed as 15 mcg subcutaneously daily combined with standard doses of RBV. Mean treatment duration was 21 weeks; CIFN was discontinued within 4 weeks in 24%. Hematological growth factors were used in 49%. Post-treatment viral loads were available in 385 patients. SVR to CIFN/RBV was achieved in 11%, and was significantly higher in prior PEG-IFN/RBV relapsers compared with nonresponders (31% vs. 6%, respectively; P<0.0001). A 2-log10 or greater drop in HCV RNA after 24 weeks of PEG-IFN/RBV was a predictor of subsequent SVR to CIFN/RBV.
CONCLUSIONS: CIFN/RBV was used frequently in clinical practice for retreatment of PEG-IFN/RBV. In this setting, early treatment discontinuation was common. Overall SVR was low, although response was significantly better in prior PEG-IFN/RBV relapsers and those who had a 2-log(10) or greater decline than in nonresponders.

BACKGROUND: Patients with chronic hepatitis C genotype 1 (HCV-1) and difficult-to-treat characteristics respond poorly to pegylated interferon alfa and ribavirin (RBV), and could benefit from an interferon with increased activity (consensus interferon or CIFN), favorable viral kinetics from daily dosing, and a longer duration of therapy. The purpose of this pilot study was to determine the efficacy and safety of daily CIFN + RBV for initial treatment of patients with HCV-1 infection.
METHODS: Patients with difficult-to-treat characteristics (92% male, 33% African American, 78% Veterans Affairs [VA]; 67% high viral load, 59% stage 3-4 fibrosis, and mean weight of 204 lbs) were enrolled at seven VA and two community medical centers. They were randomized to daily CIFN (15 mcg/day SQ) and RBV (1-1.2 g/d PO) given for either 52 weeks (group A, n = 33) or 52-72 weeks (from time of viral response +48 weeks) (group B, n = 31).
RESULTS: Intention to treat analysis for treatment groups A and B demonstrated 33% (11/33) and 32% (10/31) sustained virologic response (SVR), respectively. Only 2/31 patients in group B received more than 52 weeks of treatment. The overall group demonstrated a 31% (20/64) rapid virologic response rate (RVR), 54% (34/64) end of treatment virologic response and a 33% (21/64) SVR. Patients with RVR at 4 weeks, early virologic response from 8-12 weeks, and late virologic response from 16-24 weeks demonstrated SVR of 75% (15/20), 31% (4/13), and 22% (2/9), respectively. Overall early non-protocol discontinuation occurred in 26/64 (40%) patients.
CONCLUSIONS: Daily CIFN and ribavirin for initial treatment of HCV-1 patients has potential for achieving a relatively high RVR rate, but discontinuations are frequent and successful use of this regimen is highly dependent on adequate patient support to maintain adherence.

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BACKGROUND: About one-half of patients with hepatitis C genotype 1 and one-third with genotype 2/3 have treatment failure with peginterferon alpha and ribavirin. Consensus interferon (CIFN) is an option for retreatment of these patients.
OBJECTIVE: To summarize comparative safety and efficacy of different regimens of CIFN for the treatment of patients with chronic hepatitis C infection.
METHODS: Medline, Scopus, ISI, and Cochran Central Register of Clinical Trials were used.
METHODS: Randomized clinical trials (RCTs) were eligible for inclusion in the study.
METHODS: HIV and HBV seronegative patients with positive HCV-RNA during the 6 months before the start of the study were eligible for inclusion.
METHODS: Different regimens of CIFN were studied.
METHODS: Studies were appraised based on methods of random sequence generation, allocation concealment, and blinding. The random effects model of DerSimonian and Laird was employed to run the meta-analysis. The end-point was sustained virological response (SVR).
RESULTS: Data of 10 RCTs including 1,600 subjects were extracted. High daily induction dose regimen of CIFN did not yield a higher rate of SVR than low daily induction dose treatment regimen, RR = 0.83 (95% CI 0.58-1.17). A dose of 9 μg thrice weekly (tiw) was associated with a significantly higher rate of SVR compared with 3 μg [RR = 3.14 (95% CI 1.68-5.58)][Symbol: see text]. Withdrawal rate was similar [RR = 1.28 (95% CI 0.65-2.50)] but dose modification was higher in 9 μg [RR = 3.22 (95% CI 1.08-9.60)]. A dose of 18/15 μg tiw was not more effective than 9 μg over a similar treatment duration [RR = 1.02 (95% CI 0. 87-1.19)].
CONCLUSIONS: Limitations include inadequate reporting of methodological information and side effects, lack of publication bias assessment due to the small number of studies in each analysis.
CONCLUSIONS: High dose daily induction therapy with CIFN is not superior to low dose therapy in terms of SVR. It seems that 9 μg tiw is the optimal treatment dose of CIFN for treatment of HCV infection. Optimal duration and safety profile of CIFN therapy have yet been elucidated.

Treatment is initiated when the McDonald criteria for relapsing-remitting multiple sclerosis (RRMS) are fulfilled. High-risk patients with clinically isolated syndrome are followed using magnetic resonance imaging for one year after the first imaging. Interferon-beta or glatiramer acetate are the first-line immunomodulating drugs (IMD) for RRMS. MxA protein is measured 12 and 24 months after initiation of Interferon-beta to evaluate possible development of neutralizing antibodies. If MxA protein may not be detected repeatedly interferon-beta treatment is discontinued. If the disease is active in spite of treatment with first-line IMD, natalizumab may be considered as a second-line therapy. IMD is stopped when the transition to secondary progressive phase has occurred (or upon transition to secondary progressive phase).

BACKGROUND: Consensus interferon (CIFN) is a newly developed type I interferon.
OBJECTIVE: This multicentre, controlled trial was conducted to determine the efficacy of CIFN and to compare it with alpha-1b-interferon (IFN-alpha1b) in the treatment of patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B.
METHODS: 144 Patients were randomly assigned to receive 9 microg CIFN (CIFN group) or 50 microg INF-alpha1b (IFN-alpha group) subcutaneously 3 times weekly for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by normalization of serum alanine transaminase (ALT) levels and the non-detectability of serum hepatitis B virus DNA or HBeAg at the end of treatment and 24 weeks after stopping treatment.
RESULTS: There was no statistically significant difference in the serological, virological and biochemical parameters between CIFN and IFN-alpha1b groups at the end of the therapy and follow-up period (p > 0.05). Overall, at the end of treatment, 7.0% (5/71) and 35.2% (25/71) of patients in the CIFN group showed a complete or partial response compared with 7.4% (5/68) and 33.8% (23/68) of the IFN-alpha group (p = 0.10). At 24 weeks after stopping treatment, 6.9% (5/72) and 37.5% (27/72) of patients in the CIFN group showed complete response or partial response compared with 7.1% (5/70) and 34.3% (24/70) of the IFN-alpha group (p = 0.10).
CONCLUSIONS: These findings suggest that 9 microg CIFN is effective in the treatment of patients with HBeAg-positive chronic hepatitis B. It can gradually induce ALT normalization and HBV DNA clearance and HBeAg loss or HBeAg/HBeAb seroconversion.

OBJECTIVE: Thyroid disorders represent a common side effect of antiviral therapy in patients with chronic hepatitis C (CHC). However, there is strong evidence for a higher prevalence of thyroidal antibodies (TA) and nonorgan-specific autoantibodies (NOSA) even before interferon (IFN) administration. Here, we report for the first time on the distribution and occurrence of TA and NOSA before, during, and after treatment with daily highdosed IFN alfacon-1 [consensus IFN (CIFN)].
METHODS: Thyrotropin (TSH) levels and antibodies to different autoantigens were analyzed in 217 patients with CHC (29.8% females) who were treated with CIFN induction therapy (27 or 18 mg q.d.).
RESULTS: Pretreatment abnormal TSH levels (TSH>3.0 mU/L or <0.4 mU/L) were detected in 15.6% and occurred significantly more often in females (24.6%; P=0.018). TA could be detected only in 2.6%, NOSA in up to 29.9% (47.4% females vs. 24.2% males). During CIFN induction therapy, low TSH levels were detected in 14.1% whereas elevated TSH levels occurred later (week 48) in up to 15.5%, again preferentially in females (42%, P=0.005). In 1.4% of all patients, treatment had to be discontinued because of symptomatic hyperthyroidism. TAs were detected in 10.5% (30.5% females) and NOSA up to 58% during CIFN treatment.
CONCLUSIONS: During CIFN induction therapy, alterations in TSH levels and an increased prevalence of TA and NOSA are quite common, especially in females. Clinically relevant symptoms occur, however, only in a small number (1.4%). Thus, treatment with daily and high-dose CIFN does not appear to increase the incidence of (severe) thyroidal or other autoimmune disorders compared with standard IFN in patients with CHC.

BACKGROUND: Current treatments for chronic hepatitis C virus (HCV) employing pegylated interferon (PEG-IFN) plus ribavirin are successful in approximately 50% of patients. Consensus IFN (CIFN) is a recombinant type I IFN that has demonstrated efficacy where conventional therapy has failed. We evaluated the host cell antiviral response and anti-HCV actions induced by IFN-alpha2a, PEG-IFN-alpha2b or CIFN on cultured immortalized human hepatocytes, Huh7 human hepatoma cells and Huh7 cells that harboured genetically distinct HCV RNA replicons or were infected with HCV 2a.
METHODS: Cultured cells were treated with each IFN at relevant dosing based upon the pharmacological attainable in vivo serum maximum IFN concentrations. Gene expression and antiviral properties were measured using protein, RNA and virus quantification assays.
RESULTS: CIFN treatment maximally triggered Janus kinase signal transducer and activator of transcription signalling in association with enhanced IFN-stimulated gene (ISG) expression. Increased antiviral potency of CIFN was associated with enhancement of IFN-induced blockade upon viral protein synthesis, protection of the cellular IFN promoter stimulator-1 (IPS-1) protein from HCV proteolysis and reduced replication of an IFN-resistant HCV replicon variant. Microarray analyses revealed that CIFN treatment induced a distinct pattern of ISG expression in cultured hepatocytes compared with other IFNs.
CONCLUSIONS: CIFN exhibits increased anti-HCV potency over IFN-alpha2a and PEG-IFN through maximal and distinct induction of ISG expression and enhanced intracellular innate antiviral response, while protecting IPS-1 from HCV proteolysis. CIFN might offer a treatment regimen imparting translational control programmes and restoration of the retinoic acid-inducible gene-1/IPS-1 pathway and could be considered for previous treatment failures.

The pharmacokinetic properties of a branched 40 kDa polyethylene glycol (PEG) conjugate formulation of consensus interferon-alpha (CIFN) was evaluated in rhesus monkeys following subcutaneous administration. Four groups of rhesus monkeys (n=6 per group) received 1250, 300 and 150 microg/kg of PEG-CIFN and 150 microg/kg CIFN, respectively. Serum concentrations of the interferons were measured with an antiviral activity assay at various time points after administration. The PK profiles of the pooled data were described by a noncompartmental method. Peak concentration of PEG-CIFN was observed at 27-31 h, followed by a prolonged decay in comparison with the unmodified CIFN, the PEG-CIFN had a 4-5-fold longer terminal half-life. The apparent clearance (dose(sc)/AUC) decreased from 150 mL/h/kg for CIFN to 19.0-45.5 mL/h/kg for PEG-CIFNs. The AUC was lower for PEG-CIFN than that for CIFN at the 150 microg/kg.