title: A novel therapeutic hepatitis B vaccine induces cellular and humoral immune responses and breaks tolerance in hepatitis B virus (HBV) transgenic mice.
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.
authors.affiliation: Rhein Biotech GmbH, Duesseldorf, Germany. pbuchmann@eu.dynavax.com
authors.forename: Pascale
authors.initials: P
authors.lastname: Buchmann
authors.forename: Claudia
authors.initials: C
authors.lastname: Dembek
authors.forename: Larissa
authors.initials: L
authors.lastname: Kuklick
authors.forename: Clemens
authors.initials: C
authors.lastname: Jäger
authors.forename: Raindy
authors.initials: R
authors.lastname: Tedjokusumo
authors.forename: Miriam John
authors.initials: MJ
authors.lastname: von Freyend
authors.forename: Uta
authors.initials: U
authors.lastname: Drebber
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Janowicz
authors.forename: Karl
authors.initials: K
authors.lastname: Melber
authors.forename: Ulrike
authors.initials: U
authors.lastname: Protzer
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002784:Cholesterol / Q000008:administration & dosage*; D016207:Cytokines / Q000378:metabolism; D004338:Drug Combinations; D006510:Hepatitis B Antibodies / Q000097:blood; D006512:Hepatitis B Core Antigens / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000628:therapy*; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D008099:Liver / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010743:Phospholipids / Q000008:administration & dosage*; D012503:Saponins / Q000008:administration & dosage*; D013154:Spleen / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D004338:Drug Combinations; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; C493786:ISCOMATRIX; D010743:Phospholipids; D012503:Saponins; D002784:Cholesterol