Abstract
Despite recent advances in the chemotherapy of chronic hepatitis B (CHB), an effective viral suppression after cessation of therapy has not yet been achieved. To investigate whether hepatitis B virus (HBV)-specific T-cell responses are inducible and can contribute to the viral suppression after cessation of the therapy, we conducted a proof-of-concept study with a DNA vaccine comprising of most HBV genes plus genetically engineered interleukin-12 DNA (IL-12N222L) in 12 CHB carriers being treated with lamivudine (LAM). When the ex vivo and/or cultured IFN-γ enzyme-linked immunospot (ELISPOT) assay was performed, the detectable HBV-specific IFN-γ secreting T-cell responses were observed at the end of treatment and during a follow-up. These type 1T-cell responses, particularly CD4+ memory T-cell responses could be maintained for at least 40 weeks after the therapy and correlated with virological responses, but not with alanine aminotransferase elevation. Moreover, DNA vaccination under LAM treatment appeared to be well-tolerated and showed 50% of virological response rate in CHB carriers. Thus, a combination therapy of the DNA vaccine with chemotherapy may be one of new immunotherapeutic methods for the cure of CHB.
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Abbreviations
- ALT:
-
alanine aminotransferase
- CHB:
-
chronic hepatitis B
- CTL:
-
cytotoxic T lymphocyte
- ELISPOT:
-
enzyme-linked immunospot
- Env:
-
envelope
- HBeAg:
-
hepatitis B virus e antigen
- HBsAg:
-
hepatitis B virus surface antigen
- HBV:
-
hepatitis B virus
- HBc:
-
hepatitis B virus core
- HCV:
-
hepatitis C virus
- IL-12:
-
interleukin-12
- IFN:
-
interferon
- ISC:
-
IFN-γ secreting cell
- LAM:
-
lamivudine
- PBMC:
-
peripheral blood mononuclear cell
- PCR:
-
polymerase chain reaction
- Pol:
-
polymerase
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Acknowledgements
We thank Dr M Tschaika, E-J Lee, S-Y Eum, and Dr N Opanasyuk for their assistance in processing this study and to Drs J-W Youn and H-T Jin for their revision of the report. This work was supported by grants from National Research Laboratory program of National S&T Program of the Ministry of Science and Technology (2000-N-NL-01-C-202), the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (0405-DB00-0101-0011), the International Cooperation Research Program of the Ministry of Science & Technology (M60401000227-05A0100-22710), POSCO (2000Y013), and Consortium Project (Genexine Co. Ltd, Daewoong Pharm. Co. Ltd, Dong-A Pharm. Co. Ltd, and POSCO).
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Yang, SH., Lee, CG., Park, SH. et al. Correlation of antiviral T-cell responses with suppression of viral rebound in chronic hepatitis B carriers: a proof-of-concept study. Gene Ther 13, 1110–1117 (2006). https://doi.org/10.1038/sj.gt.3302751
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DOI: https://doi.org/10.1038/sj.gt.3302751
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