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Buchmann, P.* ; Dembek, C.J. ; Kuklick, L.* ; Jager, C.* ; Tedjokusumo, R. ; von Freyend, M.J.* ; Drebber, U.* ; Janowicz, Z.* ; Melber, K.* ; Protzer, U.

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)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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
Sprache englisch
Veröffentlichungsjahr 2013
HGF-Berichtsjahr 2013
ISSN (print) / ISBN 0264-410X
e-ISSN 1358-8745
Zeitschrift Vaccine
Quellenangaben Band: 31, Heft: 8, Seiten: 1197-1203 Artikelnummer: , Supplement: ,
Verlag Elsevier
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
POF Topic(s) 30203 - Molecular Targets and Therapies
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-502700-003
G-520100-001
G-502700-004
PubMed ID 23306359
DOI 10.1016/j.vaccine.2012.12.074
WOS ID WOS:000315312500009
Scopus ID 84873088935
Erfassungsdatum 2013-03-21
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