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Backes, S. ; Jager, C. ; Dembek, C.J. ; Kosinska, A. ; Bauer, T. ; Stephan, A.-S. ; Dišlers, A.* ; Mutwiri, G.* ; Busch, D.H. ; Babiuk, L.A.* ; Gasteiger, G. ; Protzer, U.

Protein-prime/modified vaccinia virus Ankara vector-boost vaccination overcomes tolerance in high-antigenemic HBV-transgenic mice.

Vaccine 34, 923-932 (2016)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
BACKGROUND: Therapeutic vaccination is a novel treatment approach for chronic hepatitis B, but only had limited success so far. We hypothesized that optimized vaccination schemes have increased immunogenicity, and aimed at increasing therapeutic hepatitis B vaccine efficacy. METHODS: Modified Vaccinia virus Ankara (MVA) expressing hepatitis B virus (HBV) antigens was used to boost protein-prime vaccinations in wildtype and HBV-transgenic (HBVtg) mice. RESULTS: Protein-prime/MVA-boost vaccination was able to overcome HBV-specific tolerance in HBVtg mice with low and medium but not with high antigenemia. HBV-specific antibody titers, CD8+ T-cell frequencies and polyfunctionality inversely correlated with HBV antigen levels. However, optimization of the adjuvant formulation, increasing the level of antigen expression and utilization of HBsAg of heterologous subtype induced HBV-specific CD8+ and CD4+ T-cells and neutralizing antibodies even in high-antigenemic HBVtg mice. CONCLUSIONS: Our results indicate that high HBV antigen levels limit the immunological responsiveness to therapeutic vaccination but optimization of the vaccine formulation can overcome tolerance even in the presence of high antigenemia. These findings have important implications for the development of future therapeutic hepatitis B vaccination strategies and potentially also for the stratification of chronic hepatitis B patients for therapeutic vaccination.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Hepatitis B Virus ; Heterologous Prime/boost Strategy ; Recombinant Mva ; Therapeutic Vaccination ; Tolerance; Hepatitis-b-virus; Cytotoxic T-lymphocytes; Surface-antigen; In-vivo; Immune-responses; Dendritic Cells; Infection; Lamivudine; Immunization; Replication
ISSN (print) / ISBN 0264-410X
e-ISSN 1358-8745
Journal Vaccine
Quellenangaben Volume: 34, Issue: 7, Pages: 923-932 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Oxford
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)