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Correlation of antiviral T-cell responses with suppression of viral rebound in chronic hepatitis B carriers: a proof-of-concept study

Gene Therapy volume 13, pages 1110–1117 (2006)Cite this article

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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Authors and Affiliations

  1. Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk, Korea

    S-H Yang, C-G Lee, S-H Park, S-J Im, Y-M Kim, J-M Son & Y-C Sung

  2. Department of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, Korea

    J-M Son, J-S Wang & S-K Yoon

  3. Department of Molecular Microbiology, International Vaccine Institute, Seoul, Korea

    M-K Song

  4. Department of Infectious Diseases and Microbiology, Vilnius University, Vilnius, Lithuania

    A Ambrozaitis

  5. Department of Gastroenterology and Diet Therapy of Kiev Medical Academy, Kiev, Ukraine

    N Kharchenko

  6. Division of Molecular Life Science, Ewha Woman's University, Seoul, Korea

    Y-D Yun

  7. Research Institute, National Cancer Center, Gyeonggi, Korea

    C-M Kim

  8. Research Laboratories, Dong-A Pharm. Co., Ltd, Yongin-si, Gyeonggi, Korea

    C-Y Kim, S-H Lee, B-M Kim & W-B Kim

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Correspondence to Y-C Sung.

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Supplementary information accompanies the paper on Gene Therapy website (http://www.nature.com/gt)

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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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