Article

Buchmann P, Dembek C, Kuklick L, et al. A novel therapeutic hepatitis B vaccine induces cellular and humoral immune responses and breaks tolerance in hepatitis B virus (HBV) transgenic mice

Rhein Biotech GmbH, Duesseldorf, Germany. Electronic address: .
Vaccine (Impact Factor: 3.62). 01/2013; 31(8). DOI: 10.1016/j.vaccine.2012.12.074
Source: PubMed

ABSTRACT

Therapeutic vaccines are currently being developed for chronic hepatitis B and C. As an alternative to long-term antiviral treatment or to support only partially effective therapy, they should activate the patient's immune system effectively to fight and finally control the virus. A paradigm of therapeutic vaccination is the potent induction of T-cell responses against key viral antigens - besides activation of a humoral immune response. We have evaluated the potential of a novel vaccine formulation comprising particulate hepatitis B surface (HBsAg) and core antigen (HBcAg), and the saponin-based ISCOMATRIX™ adjuvant for its ability to stimulate T and B cell responses in C57BL/6 mice and its ability to break tolerance in syngeneic HBV transgenic (HBVtg) mice. In C57BL/6 mice, the vaccine induced multifunctional HBsAg- and HBcAg-specific CD8+ T cells detected by staining for IFNγ, TNFα and IL-2, as well as high antibody titers against both antigens. Vaccination of HBVtg animals induced potent HBsAg- and HBcAg-specific CD8+ T-cell responses in spleens and HBcAg-specific CD8+ T-cell responses in livers as well as anti-HBs seroconversion two weeks post injection. Vaccination further reduced HBcAg expression in livers of HBVtg mice without causing liver damage. In summary, this study demonstrates therapeutic efficacy of a novel vaccine formulation in a mouse model of immunotolerant, chronic HBV infection.

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Available from: Ulrike Protzer, Apr 26, 2015
    • "HBVtg mice replicate HBV in hepatocytes , produce HBcAg, HBsAg and hepatitis B e antigen (HBeAg) and release infectious virus into the blood[5]. Expression of HBV antigens starts around birth and mice are immunologically tolerant to HBV-encoded proteins[5,6], but this tolerance can be broken[7,8]. In this study, we developed a highly efficient prime-boost vaccination strategy aiming at the induction of neutralizing antibodies and effector CD8+ and CD4+ T-cell responses. "
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