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标题: A pilot randomized controlled trial of dual-plasmid HBV DNA vaccine mediated by [打印本页]

作者: StephenW 时间: 2012-7-26 06:32 标题: A pilot randomized controlled trial of dual-plasmid HBV DNA vaccine mediated by

A pilot randomized controlled trial of dual-plasmid HBV DNA vaccine mediated by in vivo electroporation in chronic hepatitis B patients under lamivudine chemotherapy

F.-Q. Yang1,†,
Y.-Y. Yu2,†,
G.-Q. Wang2,
J. Chen3,
J.-H. Li4,
Y.-Q. Li5,
G.-R. Rao1,
G.-Y. Mo1,
X.-R. Luo1,
G.-M. Chen1

Article first published online: 26 FEB 2012

1 Liver Disease Research Center, Guangzhou 458 Hospital, Guangzhou, China
2 Department of Infectious Diseases, Peking University First Hospital, Beijing, China
3 Ditan Hospital, Beijing, China
4 Youan Hospital, Beijing, China
5 Beijing 302 Hospital, Beijing, China

† These authors contributed equally to this paper.

*Xian-Rong Luo and Guang-Ming Chen, Liver Disease Research Center, Guangzhou 458 Hospital, Guangzhou 510600, China. E-mail: [email protected]

Keywords:

chronic hepatitis B;
DNA vaccine;
hepatitis B virus;
lamivudine-resistant mutants;
T cell

Summary. A DNA vaccine against the hepatitis B virus (HBV), enhanced by IL-2/IFN-γ fusion protein expression from a plasmid construct and mediated by in vivo electroporation, was evaluated in a total of 39 HBeAg-positive patients with chronic hepatitis B (CHB). The six of 39 patients with a serum alanine aminotransferase (ALT) value of 1–2 times upper limit of normal (ULN) were assigned to the open-label arm (Group01) receiving vaccine monotherapy; the remaining 33 patients with an ALT of more than two times ULN were enroled to the randomized and controlled arm (Group02) receiving lamivudine (LAM) monotherapy (LAM+placebo) or combined therapy (LAM+DNA vaccine) in 1:2 ratio. In Group01, a significant elevation of HBV-specific IFN-γ-secreting T-cell counts in comparison with baseline was observed. In Group02, the proportion of patients with HBV DNA suppression was higher with LAM+DNA vaccine than with LAM monotherapy at each visit time point after the final injection of DNA vaccine at week 36, revealing a significant difference between the two groups (P =0.03) at week 60. The incidence of dual-site mutations of rtM204/I/S+rtL180M was significantly lower (P =0.03) with an identified lower virological breakthrough (VBT) rate (P =0.03) in patients receiving LAM+DNA vaccine than LAM monotherapy, accompanied with a significant higher positive T-cell response rate in patients receiving LAM+DNA vaccine (P =0.03). In conclusion, this study provides evidence that HBV DNA vaccination is safe and immunologically effective, and that the HBV-specific T-cell responses induced by DNA vaccination under LAM chemotherapy showed a correlation with the suppression of viral replication in patients with CHB.

作者: StephenW 时间: 2012-7-26 06:33

综述。针对增强IL-2/IFN-γ融合蛋白表达质粒的构建和体内电穿孔介导的乙型肝炎病毒（HBV），DNA疫苗进行了评价，在总共39例HBeAg阳性患者，慢性乙型肝炎（HBV）。开放标签ARM（Group01的）接受疫苗单一，其余33例患者的ALT更与血清丙氨酸转氨酶（ALT）值的1-2倍正常上限（ULN）的患者被分配到639报读超过两倍ULN的随机对照组（Group02）（林+安慰剂）接受拉米夫定（LAM）单药治疗或联合治疗（林+ DNA疫苗）的比例为1:2。在Group01的观察，与基线相比HBV特异性IFN-γ分泌性T细胞计数显着升高。 Group02，HBV DNA抑制患者的比例高于单药治疗后，最终在第36周DNA疫苗注射在每次访问的时间点，林与林+ DNA疫苗，露出了两组之间的显着差异（P= 0.03 ）60周。双点突变的rtM204/I/S+ rtL180M的发病率显着降低（P= 0.03），确定较低的病毒学突破率（VBT组）在接受林的患者（p = 0.03）+比林单用DNA疫苗，伴随着1显著较高的阳性T细胞在接受林+ DNA疫苗（p = 0.03）的患者反应率。在最后，这项研究提供的证据，HBV DNA疫苗是安全有效的免疫，下林化疗DNA疫苗诱导的HBV特异性T细胞反应，表明具有抑制病毒复制的慢性乙型肝炎患者的相关性。

作者: 咬牙硬挺 时间: 2012-7-26 06:46

感谢分享。

作者: rocgao 时间: 2012-7-26 11:52

是广药的dna疫苗吧？怎么没报道hbeag转阴率呢

作者: StephenW 时间: 2012-7-26 16:27

本帖最后由 StephenW 于 2012-7-26 16:27 编辑

回复 rocgao 的帖子

我不知道。HBeAg血清转换的数字不在总结中说，可能在全篇论文中.

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