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Abstract

Background: Treatment regimens for chronic hepatitis B virus (HBV) infection are efficient in suppressing viral load and improving hepatocellular injury and its complications. However, current antiviral agents such as nucleos(t)ide analogues or interferon-alpha are inefficient to reconstitute immunologic control of a persistent HBV infection or mediate clearance of HBV-DNA. It was hypothesized that high levels of circulating HBV surface antigens (HBsAg) produced by episomal and integrated HBV-DNA lead to immune tolerance of HBV and contribute to chronic HBV infection. Hence, low level HBsAg in a fraction of patients may create a window for the reconstitution of an HBV-specific response and control of infection. Previous studies in transplant patients indicate that antiviral therapy, in combination with a third generation PreS/S vaccine, may control HBV viremia and induce seroconversion to anti-HBs.
Methods: We determined the frequency of low level HBsAg (<500 IU/mL) carriers by a data request in two diagnostic laboratories. Three HBsAg positive, NUC treated, low level HBsAg carriers were immunized with 6 to 11 doses of Sci-B-VacTM. The kinetics of HBsAg reduction, anti-HBs seroconversion and T cell response after vaccination was determined.
Results: Approximately 30% of patients with chronic hepatitis B in two large cohorts showed low HBsAg concentrations of <500 IU/mL. Three low level HBsAg carriers with baseline concentrations of 448, 20.2 and 19.2 IU/mL HBsAg seroconverted to anti-HBs after being vaccinated with Sci-B-VacTM. Two years after vaccination, the anti-HBs titer was 100, 600 and 260 IU/L, respectively.
Conclusion: These preliminary data suggest that combining NUC´s with PreS1/PreS2/S vaccination in low level carriers of HBsAg may provide a new therapy to achieve functional control of chronic hepatitis B by seroconversion to anti-HBs.

Keywords: Hepatitis B; Therapeutic vaccination; HBV PreS1/S2/S