Abstract：
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.
journal_name
Vaccinejournal_title
Vaccineauthors
Backes S,Jäger C,Dembek CJ,Kosinska AD,Bauer T,Stephan AS,Dišlers A,Mutwiri G,Busch DH,Babiuk LA,Gasteiger G,Protzer Udoi
10.1016/j.vaccine.2015.12.060subject
Has Abstractpub_date
2016-02-10 00:00:00pages
923-32issue
7eissn
0264-410Xissn
1873-2518pii
S0264-410X(15)01871-Xjournal_volume
34pub_type
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