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本帖最后由 StephenW 于 2012-8-10 14:36 编辑
http://jvi.asm.org/content/86/17/9297.abstract?etoc
DNA Prime-Adenovirus Boost Immunization Induces a Vigorous and Multifunctional T-Cell Response against Hepadnaviral Proteins in the Mouse and Woodchuck Model
Anna D. Kosinska a,
Lena Johrden b,
Ejuan Zhang a, c,
Melanie Fiedler a,
Anja Mayer a,
Oliver Wildner b,d,
Mengji Lu a and
Michael Roggendorf a
- Author Affiliations
a Institute of Virology, University Hospital of Essen, Essen, Germany
b Department of Molecular and Medical Virology, Institute of Microbiology and Hygiene, Ruhr University Bochum, Bochum, Germany
c Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China
d Paul Ehrlich Institute, Division of Medical Biotechnology, Langen, Germany
ABSTRACT
Induction of hepatitis B virus (HBV)-specific cytotoxic T cells by therapeutic immunization may be a strategy to treat chronic hepatitis B. In the HBV animal model, woodchucks, the application of DNA vaccine expressing woodchuck hepatitis virus (WHV) core antigen (WHcAg) in combination with antivirals led to the prolonged control of viral replication. However, it became clear that the use of more potent vaccines is required to overcome WHV persistence. Therefore, we asked whether stronger and more functional T-cell responses could be achieved using the modified vaccines and an optimized prime-boost vaccination regimen. We developed a new DNA plasmid (pCGWHc) and recombinant adenoviruses (AdVs) showing high expression levels of WHcAg. Mice vaccinated with the improved plasmid pCGWHc elicited a stronger WHcAg-specific CD8+ T-cell response than with the previously used vaccines. Using multicolor flow cytometry and an in vivo cytotoxicity assay, we showed that immunization in a DNA prime-AdV boost regimen resulted in an even more vigorous and functional T-cell response than immunization with the new plasmid alone. Immunization of naïve woodchucks with pCGWHc plasmid or AdVs induced a significant WHcAg-specific degranulation response prior to the challenge, this response had not been previously detected. Consistently, this response led to a rapid control of infection after the challenge. Our results demonstrate that high antigen expression levels and the DNA prime-AdV boost immunization improved the T-cell response in mice and induced significant T-cell responses in woodchucks. Therefore, this new vaccination strategy may be a candidate for a therapeutic vaccine against chronic HBV infection.
FOOTNOTES
Received 28 February 2012.
Accepted 11 June 2012.
Address correspondence to Michael Roggendorf, [email protected].
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发表于 2012-8-10 14:35
