title: HCV E1E2-MF59 vaccine in chronic hepatitis C patients treated with PEG-IFNα2a and Ribavirin: a randomized controlled trial.
abstract: 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 E1E2MF59 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 E1E2MF59 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.
authors.affiliation: Hepatology Unit, University Hospital of Pisa, Pisa, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Colombatto
authors.forename: M R
authors.initials: MR
authors.lastname: Brunetto
authors.forename: A M
authors.initials: AM
authors.lastname: Maina
authors.forename: V
authors.initials: V
authors.lastname: Romagnoli
authors.forename: P
authors.initials: P
authors.lastname: Almasio
authors.forename: M G
authors.initials: MG
authors.lastname: Rumi
authors.forename: A
authors.initials: A
authors.lastname: Ascione
authors.forename: G
authors.initials: G
authors.lastname: Pinzello
authors.forename: M
authors.initials: M
authors.lastname: Mondelli
authors.forename: L
authors.initials: L
authors.lastname: Muratori
authors.forename: R
authors.initials: R
authors.lastname: Rappuoli
authors.forename: D
authors.initials: D
authors.lastname: Rosa
authors.forename: M
authors.initials: M
authors.lastname: Houghton
authors.forename: S
authors.initials: S
authors.lastname: Abrignani
authors.forename: F
authors.initials: F
authors.lastname: Bonino
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D057134:Antibodies, Neutralizing / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D018937:Hepatitis C Antibodies / Q000097:blood; D019698:Hepatitis C, Chronic / Q000628:therapy*; D006801:Humans; D007273:Injections, Intramuscular; D016898:Interferon-alpha / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011136:Polysorbates / Q000008:administration & dosage* / Q000009:adverse effects; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D013185:Squalene / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D019562:Viral Load
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000998:Antiviral Agents; D018937:Hepatitis C Antibodies; D016898:Interferon-alpha; C089950:MF59 oil emulsion; D011136:Polysorbates; D012367:RNA, Viral; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D014761:Viral Hepatitis Vaccines; D011092:Polyethylene Glycols; D012254:Ribavirin; D013185:Squalene; C100416:peginterferon alfa-2a
keywords: HCV; immune response; interferon; neutralizing antibodies; vaccine; viral kinetics
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