Immunogenicity and tolerability of intradermal administration of an HCV E1-based vaccine candidate in healthy volunteers and patients with resolved or ongoing chronic HCV infection.

The tolerability and immunogenicity of intradermal injections of a candidate HCV vaccine, based on the E1 protein of the hepatitis C virus (HCV), was examined in an exploratory study in healthy volunteers, in subjects with a history of resolved HCV infection, and in patients suffering from therapy-resistant chronic HCV. Sub-epidermal injection of three doses of 4 microg of non-adjuvanted E1 vaccine induced much weaker humoral and cellular immune responses in healthy subjects and chronic HCV patients than the intramuscular administration of 20 microg E1 formulated on alum. However, in three subjects who cleared HCV infection, intradermal administration of this low dose of E1 induced rapid and clear anamnestic responses. These data demonstrate that E1-specific immune responses can be induced in resolving HCV infections and that memory (B and T) cells can be restimulated with suboptimal doses of E1 antigen.

A pilot study of therapeutic vaccination with envelope protein E1 in 35 patients with chronic hepatitis C.

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 mug 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 < or =.01). In conclusion, E1 therapeutic vaccination is well tolerated and the observed effects warrant further study.