HCV E1E2‐MF59 vaccine in chronic hepatitis C patients treated with PEG‐IFNα2a and Ribavirin: a randomized controlled trial |
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Authors: | P Colombatto M R Brunetto A M Maina V Romagnoli P Almasio M G Rumi A Ascione G Pinzello M Mondelli L Muratori R Rappuoli D Rosa M Houghton S Abrignani F Bonino |
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Institution: | 1. Hepatology Unit, University Hospital of Pisa, Pisa, Italy;2. Sezione di Gastroenterologia, Di.Bi.M.I.S., University of Palermo, Palermo, Italy;3. 1st Gastroentrology Unit ‘Ca Granda’‐ IRCCS Foundation, University of Milano, Milano, Italy;4. Liver Unit, Cardarelli Hospital, Napoli, Italy;5. Medical Department, Niguarda Hospital, Milano, Italy;6. Department of Infectious Diseases, University of Pavia, Pavia, Italy;7. Department of Clinical Medicine, ‘S.Orsola‐Malpighi’ University Hospital of Bologna, Bologna, Italy;8. Novartis, Siena, Italy;9. Canada Excellence Research Chair in Virology University of Alberta, Edmonton, AB, Canada;10. National Institute of Molecular Genetics (INGM), Milano, Italy |
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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. |
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Keywords: |
HCV
immune response interferon neutralizing antibodies vaccine viral kinetics |
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