1. ¹Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk, Korea
2. ²Department of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, Korea
3. ³Department of Molecular Microbiology, International Vaccine Institute, Seoul, Korea
4. ⁴Department of Infectious Diseases and Microbiology, Vilnius University, Vilnius, Lithuania
5. ⁵Department of Gastroenterology and Diet Therapy of Kiev Medical Academy, Kiev, Ukraine
6. ⁶Division of Molecular Life Science, Ewha Woman's University, Seoul, Korea
7. ⁷Research Institute, National Cancer Center, Gyeonggi, Korea
8. ⁸Research Laboratories, Dong-A Pharm. Co., Ltd, Yongin-si, Gyeonggi, Korea

Correspondence: Professor Y-C Sung, Division of Molecular and Life Science, Pohang University of Science and Technology, San 31, Hyoja-dong, Nam-gu, Pohang, Kyungbuk, 790-784, Korea. E-mail: ycsung@postech.ac.kr

Received 22 September 2005; Revised 2 January 2006; Accepted 21 January 2006; Published online 9 March 2006.

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- enzyme-linked immunospot (ELISPOT) assay was performed, the detectable HBV-specific IFN- 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.