免疫原性
血清转化
阿德福韦
医学
埃利斯波特
病毒学
免疫学
乙型肝炎病毒
抗体
免疫系统
乙型肝炎
dna疫苗
T细胞
病毒
免疫
拉米夫定
作者
Seung Kew Yoon,Yong Bok Seo,Se Jin Im,Si Hyun Bae,Myeong Jun Song,Chan Ran You,Jung Won Jang,Se Hwan Yang,You Suk Suh,Ji Soo Song,Byong Moon Kim,Chae Young Kim,Sook Hyang Jeong,Young Chul Sung
摘要
Abstract 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. 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.
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