In:
Liver International, Wiley, Vol. 35, No. 3 ( 2015-03), p. 805-815
Abstract:
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. Methods 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 HB eAg/anti‐ HB e were analysed. T‐cell responses were estimated by ELISPOT and FACS analysis. Results m HB ‐110 induced higher T‐cell and antibody responses than m HB ‐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 HB eAg seroconversion. One patient, who received high dose of HB ‐110 exhibited HB eAg seroconversion during vaccination, which correlated with vaccine‐induced T‐cell responses without ALT elevation. Conclusions 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 HB eAg 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.
Type of Medium:
Online Resource
ISSN:
1478-3223
,
1478-3231
DOI:
10.1111/liv.2015.35.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2124684-1
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