Journal
VACCINE
Volume 31, Issue 8, Pages 1197-1203Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2012.12.074
Keywords
HBV; ISCOMATRIX (TM) adjuvant; Protein vaccine; T cells
Categories
Funding
- Technologie-Programm Wirtschaft [PTJ-001-9910-0v08]
- German Center for Infection Research (DZIF)
- Helmholtz Alliance Immunotherapy of Cancer [HA-202]
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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 (TM) 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 IFN gamma, TNF alpha 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. (C) 2013 Elsevier Ltd. All rights reserved.
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