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RESEARCH PRODUCT

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

Lorne A. BabiukClemens JägerUlrike ProtzerSimone BackesGeorg GasteigerClaudia J. DembekDirk H. BuschAnna D. KosinskaTanja BauerAndris DishlersAnn-sophie StephanGeorge Mutwiri

subject

CD4-Positive T-Lymphocytes0301 basic medicineHBsAgHepatitis B vaccineImmunization SecondaryMice TransgenicVaccinia virusCD8-Positive T-Lymphocytesmedicine.disease_cause03 medical and health scienceschemistry.chemical_compoundAntigenNeutralization TestsImmune ToleranceAnimalsMedicineHepatitis B VaccinesHepatitis B e AntigensHepatitis B AntibodiesHepatitis B virusHepatitis B Surface AntigensGeneral VeterinaryGeneral Immunology and Microbiologybusiness.industryImmunogenicityPublic Health Environmental and Occupational Healthvirus diseasesHepatitis BHepatitis Bmedicine.diseaseAntibodies NeutralizingHepatitis B Core AntigensVirologyMice Inbred C57BLVaccination030104 developmental biologyInfectious DiseaseschemistryImmunologyMolecular MedicineVacciniabusiness

description

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.

yearjournalcountryeditionlanguage
2015-05-22Vaccine
https://doi.org/10.1016/j.vaccine.2015.12.060