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

Vaccine
Simone BackesUlrike Protzer

Abstract

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. 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. 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. 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 fut...Continue Reading

References

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Citations

Jul 22, 2016·Journal of Virology·Marianna Di ScalaGloria González-Aseguinolaza
Feb 26, 2019·Journal of Viral Hepatitis·Maria G MartinezFabien Zoulim
Mar 14, 2020·Current Opinion in HIV and AIDS·Mala K Maini, Dimitra Peppa
Aug 1, 2018·Frontiers in Immunology·Sheila F LumleyPhilippa C Matthews
Jun 15, 2019·International Journal of Molecular Sciences·Carolina BoniPaola Fisicaro
Sep 25, 2018·The Journal of Pediatrics·Hong-Yuan Hsu, Mei-Hwei Chang
Mar 9, 2021·The Journal of Allergy and Clinical Immunology·Matthew LacorciaClarissa Prazeres da Costa
May 11, 2021·Clinical and Experimental Immunology·Tamsin Cargill, Eleanor Barnes

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