RESUMO
The tolerability and immunogenicity of the hepatitis C virus E1 protein as a candidate vaccine was examined in a Phase I, single-arm study. Twenty healthy male volunteers were injected in the deltoid muscle at weeks 0, 3 and 6 with 20 microg recombinant E1 adsorbed on alum. A fourth (booster) dose was administered to 19 subjects at week 26. The candidate therapeutic vaccine was well tolerated. Three vaccine doses induced a clear humoral anti-E1 response that was boosted by a fourth dose. A strong, specific cellular immune response towards E1 was elicited in all vaccine recipients, which included a clear Th1 type response in all but one of the subjects.
Assuntos
Hepatite C/imunologia , Hepatite C/prevenção & controle , Proteínas do Envelope Viral/imunologia , Vacinas Virais/imunologia , Adolescente , Adulto , Formação de Anticorpos/imunologia , Anticorpos Anti-Hepatite C/análise , Anticorpos Anti-Hepatite C/biossíntese , Humanos , Imunidade Celular/imunologia , Imunização Secundária , Injeções Intramusculares , Interferon gama/análise , Interferon gama/biossíntese , Interleucina-5/análise , Interleucina-5/biossíntese , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Vacinas Sintéticas/imunologia , Proteínas do Envelope Viral/efeitos adversos , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversosRESUMO
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.
