The lack of effect of therapeutic vaccination with a pre-S2/S HBV vaccine in the immune tolerant phase of chronic HBV infection.

BACKGROUND/AIMS: Even if the results are controversial and preliminary, several reports suggest that the HBV vaccine might be effective in treating HBV infection. In this study, we aimed to evaluate the efficacy and safety of specific anti-HBV vaccination for the immune tolerance phase of chronic HBV infection in a randomized, controlled study. PATIENTS AND METHODS: The 47 subjects included patients that were treatment-naive with hepatitis B e antigen positivity, active hepatitis B virus replication as measured by hepatitis B virus DNA levels, persistently normal alanine transaminase levels, and with minimal or absent disease activity by liver biopsy. Thirty patients were given three intramuscular injections of 20 micro g of a pre-S2/S vaccine (GenHevac-B) on days 0, 30, and 60, and the remaining 17 patients were included in the control group. The efficacy of vaccination was evaluated by testing for loss of serum HBV DNA or decrease in its level and for HBeAg seroconversion. A significant decrease in HBV DNA levels was accepted as a decrease of >50% of initial values. The complete response was defined as loss of HBV DNA in serum with HBeAg seroconversion. Postvaccination follow-up lasted 12 months after the first dose. RESULTS: No significant effects were observed in the vaccination population in the reduction of HBV DNA to undetectable levels, or to <50% of prevaccination levels, in HBeAg/anti-HBe seroconversion, or in transaminase levels. There was an early clearance/decrease in HBV DNA levels in five vaccinated patients by 3 months, and none in controls (P = 0.143), and two of them had sustained responses later. At the end of follow-up, complete response is almost similar in study as well as control group (13% vs. 12%, P > 0.05). Disappearance of serum HBV DNA was more frequently observed in those patients who had pretreatment viremia of <100 pg/mL in both groups. The median levels of HBV DNA and alanine transaminase activity between baseline and 12 months did not differ significantly in both groups. All patients remained HBsAg positive and none developed anti-HBs. No serious adverse event was encountered in vaccinated patients, and the therapy was well tolerated. Follow-up lasted a median of 16 months (range 12-30 months) for the study group and 18 months (range 12-31months) for the control group. CONCLUSIONS: Immunotherapy with specific anti-HBV vaccine in the immune tolerance phase of chronic HBV infection did not offer additional benefit. New immunotherapeutic strategies to control HBV infection by specific HBV vaccines in chronically infected subjects are needed.