These authors contributed equally to this work.
Safety and immunogenicity of therapeutic DNA vaccine with antiviral drug in chronic HBV patients and its immunogenicity in mice
Article first published online: 29 MAR 2014
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
How to Cite
Yoon, S. K., Seo, Y. B., Im, S. J., Bae, S. H., Song, M. J., You, C. R., Jang, J. W., Yang, S. H., Suh, Y. S., Song, J. S., Kim, B. M., Kim, C. Y., Jeong, S. H. and Sung, Y. C. (2014), Safety and immunogenicity of therapeutic DNA vaccine with antiviral drug in chronic HBV patients and its immunogenicity in mice. Liver International. doi: 10.1111/liv.12530
- Article first published online: 29 MAR 2014
- Accepted manuscript online: 13 MAR 2014 03:52AM EST
- Manuscript Accepted: 9 MAR 2014
- Manuscript Received: 25 OCT 2013
- Korea Health 21 R&D project
- Ministry of Health and Welfare. Grant Number: A04-0013-AY1201-0845-00011
- chronic infection;
- DNA vaccine;
- hepatitis B;
- phase I;
- T-cell response
Background & Aims
Here, we evaluated the safety and immunogenicity of hepatitis B virus (HBV) DNA vaccine, HB-110, in mice and Korean patients with chronic hepatitis B (CHB) undergoing adefovir dipivoxil (ADV) treatment.
For animal study, mice (BALB/c or HBV transgenic) were immunized with mHB-110, and T-cell and antibody responses were evaluated. For clinical study, 27 patients randomly received either ADV alone or ADV in combination with HB-110. Liver function tests, serum HBV DNA levels and the presence of HBeAg/anti-HBe were analysed. T-cell responses were estimated by ELISPOT and FACS analysis.
mHB-110 induced higher T-cell and antibody responses than mHB-100 in mice. No adverse effects were observed by HB-110 cotreated with ADV. HBV-specific T-cell responses were induced in a portion of patients in medium to high dose of HB-110. Interestingly, HB-110 exhibited positive effects on ALT normalization and maintenance of HBeAg seroconversion. One patient, who received high dose of HB-110 exhibited HBeAg seroconversion during vaccination, which correlated with vaccine-induced T-cell responses without ALT elevation.
HB-110 was safe and tolerable in CHB patients. In contrast to results in animal models, HB-110 in Korean patients exhibited weaker capability of inducing HBV-specific T-cell responses and HBeAg seroconversion than HB-100 in Caucasian patients. As Asian patients, who are generally infected via vertical transmission, appeared to have higher level of immune tolerance than Caucasian, novel approaches for breaking immune tolerance rather than enhancing immunogenicity may be more urgently demanded to develop effective therapeutic HBV DNA vaccines.