Therapeutic potential of a combined hepatitis B virus surface and core antigen vaccine in patients with chronic hepatitis B

摘要

Purpose The safety and clinical efficacy of a vaccine containing both hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) (HBsAg/HBcAg) were evaluated in patients with chronic hepatitis B (CHB). Methods Eighteen patients with CHB were administered a vaccine containing 100 ug of HBsAg and 100(mu)g of HBcAg. The vaccine was administered ten times at 2-weekly intervals, the first five times via the nasal route only and the subsequent five times via both nasal and subcutaneous routes. The safety and efficacy of this therapeutic approach were assessed by periodic assessment of the patients' general condition, viral kinetics, and biochemical parameters during treatment and 24 and 48 weeks after therapy. The production of cytokines by peripheral blood mononuclear cells (PBMC) and antigen-pulsed dendritic cells (DC) was evaluated to assess the immuno-modulatory effects of the HBsAg/HBcAg vaccine in CHB patients. Results The HBsAg/HBcAg vaccine was safe in all patients. No flare of HBV DNA or alanine aminotransfer-ase (ALT) was recorded in any patient. Sustained HBV DNA negativity and persistently normalized ALT were detected in 9 (50 %) and 18 (100 %) patients with CHB, respectively. PBMC and HBsAg/HBcAg-pulsed DCs from HBsAg/HBcAg-vaccinated CHB patients produced significantly higher levels of various cytokines [interleukin lp (IL-1P), IL-6, IL-8, IL-12, and tumor necrosis factor a (TNF-a)] than those from control unvaccinated CHB patients (p < 0.05) after stimulation with HBsAg/HBcAg in vitro.Conclusion HBsAg/HBcAg vaccine seems a safe and efficient therapeutic approach for patients with CHB.