Z Gastroenterol 2016; 54(12): 1343-1404
DOI: 10.1055/s-0036-1597379
2. Clinical Hepatology
Georg Thieme Verlag KG Stuttgart · New York

Therapeutic Vaccination with a Third Generation PreS/S vaccine (Sci-B-VacTM) with HBV Carriers with Low-level of HBsAg result in Serovonversion to Anti-HBs

H Roggendorf
1   University Hospital TUM, Institute of Molecular Immunology, München, Germany
,
A Krawczyk
2   University Hospital Essen, University of Duisburg-Essen, Institute of Virology, Essen, Germany
,
D Shouval
3   Hadassah Medical Center, Liver Unit, Jerusalem, Israel
,
M Roggendorf
4   Technische Universität München/Helmholtz Zentrum München, Institute of Virology, München, Germany
,
G Gerken
5   University Hospital Essen, University of Duisburg-Essen, Department of Gastroenterology and Hepatology, Essen, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
19 December 2016 (online)

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Background & Aims: Chronic hepatitis B (CHB) is currently treated by IFN-α and nucleos(t)ide analogues (NUCs), however, without satisfactory results. The major problem consists in the persistence of a cccDNA in patients. Several new antiviral drugs have been developed in the recent years; however, they rarely reduce the copies of cccDNA. Therefore, cytolytic and noncytolytic approaches are needed to eliminate cccDNA from HBV-infected hepatocytes. Effective virusspecific T and B cell immune responses remain crucial in eliminating cccDNA-carrying hepatocytes and the long-term control of HBV infection. Reduction of HBV viremia by antiviral drugs provides a window for reconstitution of HBV specific immune response. Based on data obtained in our preclinical studies the combination of antiviral drugs and immunization with a third generation PreS/S vaccine (Sci-B-VacTM) may control HBV viremia during drug-off period of patients.

Methods: We immunized 4 HBsAg positve Patients with chronic Hepatitis B with Sci-B- VacTM 3-to 6 times and determined HBsAg (IU/L) and the anti-HBs antibody titers (IU/L) before immunization and after each vaccination. All patients were treated with nucleos(t)ide analogues (NUCs) at least for two years and were HBV DNA negative prior to vaccination.

Results: HBsAg concentrations before the first vaccination of the 4 immunized were 19812, 448, 20.2, 19.2 IU/l, respectively. All patients remained HBV DNA negative for the whole period of observation (at least 2 years). After three vaccinations 3 of the 4 patients seroconverted to anti-HBs. One year after onset of vaccination that antibody concentrations were 140, 80 and 150 IU/L, respectively. The patient with an initial high concentration of HBsAg did not seroconvert.

CD4 and CD8 T cell response is currently under investigation and will be presented at the meeting.

Conclusion: The HBV carriers with low-level of HBsAg and negative results for HBV DNA under NUC treatments receiving therapeutic vaccination with immunization with a third generation PreS/S vaccine (Sci-B-VacTM) seroconverted to anti-HBs. This may therefore reduce the tolerizing effect of HBsAg with respect to an appropriate T cell response. Further studies in a larger cohort including long term observation are needed to determine whether HBV cccDNA of these patients may be reduced or even eliminated.