A Pilot Study of Therapeutic Vaccination With Envelope Protein E1 in 35 Patients With Chronic Hepatitis C

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Abstract
New treatments are needed for chronic hepatitis C patients in whom viral clearance cannot be achieved. Thirty–five chronic hepatitis C patients (genotype 1) were randomized to receive 20 μg of recombinant HCV E1 (E1) (n = 26) or placebo (n = 9) intramuscularly at weeks 0, 4, 8, 12, and 24. Thirty–four then received open–label E1 vaccine at weeks 50, 53, 56, 59, 62, and 65. Twenty–four patients (12 men, 12 women; mean age, 52 y; 18 interferon–based treatment failures; mean baseline alanine aminotransferase [ALT] level, 118 IU/L) underwent a biopsy before and after 2 courses of E1, 17 months later. Liver histology was scored by 2 blinded pathologists according to the Ishak and Metavir systems. Postinjection reactions were similar to placebo (alum only). Nine of 24 patients (38%) had improvement of 2 points or more, 10 (41%) remained stable, and 5 (21%) showed worsening in total Ishak score. Nine patients (38%) improved both on Ishak and Metavir fibrosis scores. Plasma HCV–RNA levels remained unchanged, whereas ALT levels showed a trend toward a decrease during treatment. All but 3 patients developed a significant de novo E1–specific T–cell response. The increase in anti–E1 antibody levels correlated with the decrease in total Ishak score and with the relative decreases in both Ishak fibrosis score and ALT level (all P ≤ .01). In conclusion, E1 therapeutic vaccination is well tolerated and the observed effects warrant further study.