HCV E1E2-MF59 vaccine in chronic hepatitis C patients treated with PEG-IFNα2a and Ribavirin: a randomized controlled trial

被引:18
作者
Colombatto, P. [1 ]
Brunetto, M. R. [1 ]
Maina, A. M. [1 ]
Romagnoli, V. [1 ]
Almasio, P. [2 ]
Rumi, M. G. [3 ]
Ascione, A. [4 ]
Pinzello, G. [5 ]
Mondelli, M. [6 ]
Muratori, L. [7 ]
Rappuoli, R. [8 ]
Rosa, D. [8 ]
Houghton, M. [9 ]
Abrignani, S. [10 ]
Bonino, F. [11 ]
机构
[1] Univ Hosp Pisa, Hepatol Unit, Pisa, Italy
[2] Univ Palermo, Sez Gastroenterol, Di Bi MIS, Palermo, Italy
[3] Univ Milan, Ca Granda IRCCS Fdn, Gastroentrol Unit 1, Milan, Italy
[4] Cardarelli Hosp, Liver Unit, Naples, Italy
[5] Osped Niguarda Ca Granda, Dept Med, Milan, Italy
[6] Univ Pavia, Dept Infect Dis, I-27100 Pavia, Italy
[7] S Orsola Malpighi Univ Hosp Bologna, Dept Clin Med, Bologna, Italy
[8] Novartis, Siena, Italy
[9] Univ Alberta, Canada Excellence Res Chair Virol, Edmonton, AB, Canada
[10] Natl Inst Mol Genet INGM, Milan, Italy
[11] Univ Hosp Pisa, Gen Med Unit 2, Liver & Digest Div, Pisa, Italy
关键词
HCV; immune response; interferon; neutralizing antibodies; vaccine; viral kinetics; VIRAL DYNAMICS; ENVELOPE; THERAPY; REPLICATION; ALPHA; RNA;
D O I
10.1111/jvh.12163
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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), PegIFN alpha 2a-180-ug/qw and ribavirin 1000-1200-mg/qd for 48 weeks (P/R:25), or their combination (P/R + V: 30). Vaccine (100 mu g/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 (epsilon >= 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-IFN alpha 2a + 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.
引用
收藏
页码:458 / 465
页数:8
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