| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2402485 | Vaccine | 2013 | 7 Pages |
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.
► We present a novel vaccine formulation as a candidate therapeutic vaccine for hepatitis B. ► The vaccine formulation combines two particulate antigens and an adjuvant. ► We show that this vaccine formulation induces antibody as well as T cell responses. ► The novel vaccine is able to break tolerance in a mouse model of chronic hepatitis B. ► Immunogenicity and safety in a preclinical model recommend this vaccine candidate for further clinical development.
