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.
Department of Hepatology, UZ Gasthuisberg, Belgium.
Frederik
F
Nevens
Tania
T
Roskams
Hans
H
Van Vlierberghe
Yves
Y
Horsmans
Dirk
D
Sprengers
Ann
A
Elewaut
Valeer
V
Desmet
Geert
G
Leroux-Roels
Emmanuel
E
Quinaux
Erik
E
Depla
Stephanie
S
Dincq
Christine
C
Vander Stichele
Geert
G
Maertens
Frank
F
Hulstaert
D000410:Alanine Transaminase / Q000097:blood; D000917:Antibody Formation; D005260:Female; D005355:Fibrosis; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012367:RNA, Viral / Q000032:analysis; D015678:Viral Structural Proteins / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
D012367:RNA, Viral; D015678:Viral Structural Proteins; C107842:protein E1, Classical swine fever virus; D000410:Alanine Transaminase