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Hepatitis C virus ( HCV) vaccines may be able to increase viral clearance in combination with antiviral therapy. We analysed viral dynamics and HCV-specific immune response during retreatment for experienced patients in a phase Ib study with E1E2 MF59 vaccine. Seventy-eight genotype 1a/1b patients [relapsers (30), partial responders (16) and nonresponders (32) to interferon-( IFN)/ribavirin-( RBV)] were randomly assigned to vaccine ( V:23), Peg- IFNα2a-180-ug/qw and ribavirin 1000-1200-mg/qd for 48 weeks ( P/R:25), or their combination ( P/R + V:30). Vaccine (100 μg/0.5 mL) was administered intramuscularly at week 0-4-8-12-24-28-32-36. Neutralizing of binding ( NOB) antibodies and lymphocyte proliferation assay ( LPA) for E1E2-specific- CD4 + T cells were performed at week 0-12-16-48. Viral kinetics were analysed up to week 16. The vaccine was safe, and a sustained virological response ( SVR) was achieved in 4 P/R + V and 2 P/R patients. Higher SVR rates were observed in prior relapsers (P/R + V = 27.3%; P/R = 12.5%). Higher NOB titres and LPA indexes were found at week 12 and 16 in P/R + V as compared to P/R patients ( P = 0.023 and 0.025, P = 0.019 and <0.001, respectively). Among the 22 patients with the strongest direct antiviral effects of IFN (ε ≥ 0.800), those treated with P/R + V (10) reached lower HCV- RNA levels ( P = 0.026) at week 16. HCV E1E2 MF59 vaccine in combination with Peg- IFNα2a + RBV was safe and elicited E1E2 neutralizing antibodies and specific CD4 + T cell proliferation. Upon early response to IFN, vaccinations were associated with an enhanced second phase viral load decline. These results prompt phase II trials in combination with new antiviral therapies. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate whether polymorphisms of the HLA class II, tumour necrosis factor (TNF) and transporter associated with antigen processing (TAP) genes influence the response toα-interferon in patients with chronic hepatitis C. Twenty-seven sustained responders and 55 non-responders toα-interferon monotherapy were investigated. HLA-DRB1, DQA1, DQB1, TNFA, TNFB, TAP1 and TAP2 alleles were determined by PCR-based molecular techniques. Sustained virological response was defined as undetectable serum hepatitis C virus (HCV) RNA for at least 3 years after the end of treatment. Probability (P) values were corrected for the number of alleles tested (Pc). Viral genotype 1b was more frequent in responders than in non-responders (56% vs. 26%,P = 0.009). HLA-DQB1*02 occurred less frequently in responders than in non-responders (14.8% vs. 29%,Pc not significant). HLA-DRB1*11 and DQB1*0602 were found in 22.2% and 9.3% of responders and in 10.9% and 1.8% of non-responders, respectively (Pc not significant). There was no difference in the distribution of TNF alleles in the two groups. Twenty-four (88.8%) responder patients as compared with 34 (61.8%) non-responders were TAP1*0101 homozygous (Pc not significant). Thus, in European Caucasoids with chronic hepatitis C, we could not demonstrate a strong association between HLA class II, TNF, and TAP gene polymorphisms and response to interferon treatment. [ABSTRACT FROM AUTHOR]