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A novel therapeutic hepatitis B vaccine induces cellular and humoral immune responses and breaks tolerance in Hepatitis B Virus (HBV) transgenic mice.
Vaccine 31, 1197-1203 (2013)
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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Hbv ; Iscomatrix (tm) Adjuvant ; Protein Vaccine ; T Cells; Cytotoxic T-lymphocytes ; Surface-antigen ; Nucleocapsid Antigen ; Boost Vaccination ; Viral Clearance ; Core Antigen ; Cells ; Infection ; Adjuvant ; Antibody
ISSN (print) / ISBN
0264-410X
e-ISSN
1358-8745
Zeitschrift
Vaccine
Quellenangaben
Band: 31,
Heft: 8,
Seiten: 1197-1203
Verlag
Elsevier
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed