RESUMO
Chronic hepatitis C can lead to cirrhosis and hepatocellular carcinoma. We studied the safety and immunogenicity of a novel therapeutic hepatitis C virus (HCV) genotype 1a/1b consensus DNA vaccine, INO-8000, encoding HCV NS3, NS4A, NS4B, and NS5A proteins alone or co-administered with DNA-encoding IL12 (INO-9012), a human cytokine that stimulates cellular immune function, in individuals with chronic hepatitis C. This was a phase I, multisite dose-escalation trial with an expansion cohort evaluating doses of 0, 0.3, 1.0, and 3.0 mg of INO-9012 (IL12 DNA) as an addition to 6.0 mg of (INO-8000; HCV DNA vaccine). Vaccines were administered by intramuscular injection followed by electroporation at study entry and at weeks 4, 12, and 24. HCV-specific CD4+ and CD8+ T-cell immune responses were measured by IFNγ ELISpot and flow cytometry-based assays. Transient, mild-to-moderate injection site reactions unrelated to IL12 DNA dose were common. Increases in HCV-specific IFNγ production occurred in 15/20 (75%) participants. Increases in the frequency of HCV-specific CD4+ and CD8+ T cells occurred at all dose levels, with the greatest increases seen at 1.0 mg of INO-9012. HCV-specific CD8+ and CD4+ T-cell activities increased in 16/18 (89%) and 14/17 (82%) participants with available data, respectively. The vaccine regimen was safe and induced HCV-specific CD4+ and CD8+ cellular immune responses of modest magnitude in most HCV-infected participants. The addition of 1.0 mg of IL12 DNA provided the best enhancement of immune responses. The vaccine regimen had little effect on controlling HCV viremia. PREVENTION RELEVANCE: The administration of IL12 DNA along with a hepatitis C viral antigen DNA vaccine enhanced the HCV-specific immune responses induced by the vaccine in individuals with chronic hepatitis C, an important cause of hepatocellular carcinoma. IL12 could be an effective adjuvant in vaccines targeting HCV and other oncogenic viruses.
Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Vacinas de DNA , Humanos , Vacinas de DNA/efeitos adversos , Vacinas de DNA/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Carcinoma Hepatocelular/prevenção & controle , Proteínas não Estruturais Virais/genética , Neoplasias Hepáticas/prevenção & controle , Hepatite C/prevenção & controle , Hepacivirus/genética , DNA , Interleucina-12RESUMO
INTRODUCCIÓN: La vacunación frente al virus de la hepatitis B (VHB) es más efectiva en prediálisis pero en ocasiones el paciente llega a diálisis de forma no programada sin realizar vacunación completa previa. Pretendemos determinar el grado de respuesta a inmunización frente a VHB con diferentes esquemas en hemodiálisis. MATERIAL Y MÉTODOS: Estudiamos 30 pacientes en hemodiálisis administrando 2 esquemas de vacunación frente a VHB. Un grupo realiza el esquema de 3 dosis (0, 1, 6 meses) (PAUTA 3) y otro de 4 dosis (0, 1, 2, 6 meses) (PAUTA 4). RESULTADOS: El 56.7% hizo pauta 3 con respuesta del 26.7% y el 43.3% hizo pauta 4 con 23.3% de respuesta, sin diferencias significativas entre ambas (p=0.6). La tasa de AcHBs postvacunacional fue significativamente mayor con pauta 4 (p<0.05) así como en las tasas de anticuerpos mantenidas al año; a los 2 años las tasas de anticuerpos no fueron significativamente diferentes entre ambas pautas. En el resto de análisis estadístico, la vacunación realizada en pacientes con más tiempo en diálisis tuvo mayor respuesta con pauta 4 (p<0.05) aunque con respecto a los niveles de anticuerpos no hubo diferencias en los que respondieron con cada pauta. CONCLUSIONES: No existen diferencias en la respuesta inmunológica a vacunación frente VHB en hemodiálisis entre esquemas de 3 y 4 dosis. Hay mayor respuesta con el esquema de 4 dosis en la vacunación en pacientes con mayor tiempo en diálisis. Por ello, aconsejamos realizar la inmunoprofilaxis con el esquema de 3 dosis en pacientes incidentes en hemodiálisis que no han sido vacunados anteriormente
INTRODUCTION: Vaccination against hepatitis B virus (HBV) is more effective in pre-dialysis, but sometimes the patient has to start treatment in an unscheduled way, without full immunization coverage. We try to establish the immune response rate against HBV in hemodialysis with different vaccination schemes. METHODS: We studied 30 patients in hemodialysis program with 2 different vaccination schemes against HBV. One group performed a 3-doses scheme (0, 1 and 6 months) (PATTERN 3) and the other group performed a 4-doses scheme (0, 1, 2 and 6 months) (PATTERN 4). RESULTS: 56.7% performed pattern 3, with immune response of 26.7%. 43.3% performed pattern 4, with immune response of 23.3%, without significant differences between them (p=0.06). Anti-hepatitis B surface antibodies (anti-HBs) rate after vaccination was significantly higher with pattern 4 (p<0.05) as well as the antibodies counts maintained within 1 year. After 2 years, anti-HBs rates were not significantly different between both patterns. In other statical analysis, vaccination carried out in patients who have been for a long time in hemodialysis treatment, was more responsive with pattern 4 (p<0.05) although anti-HBs levels were similar in patients that had response with each pattern. CONCLUSIONS: There are no differences in immune response between 3-doses scheme and 4-doses scheme in HBV vaccination for hemodialysis patients. There is greater response with 4-doses scheme in hemodialysis patients who have not been vaccinated previously