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体内电穿孔提高针对肝炎病毒蛋白的 DNA 疫苗的治疗效力。

In vivo electroporation improves therapeutic potency of a DNA vaccine targeting hepadnaviral proteins.

机构信息

Université Lyon1, France.

出版信息

Virology. 2012 Nov 10;433(1):192-202. doi: 10.1016/j.virol.2012.07.014. Epub 2012 Aug 24.

DOI:10.1016/j.virol.2012.07.014
PMID:22921316
Abstract

This preclinical study investigated the therapeutic efficacy of electroporation (EP)-based delivery of plasmid DNA (pDNA) encoding viral proteins (envelope, core) and IFN-γ in the duck model of chronic hepatitis B virus (DHBV) infection. Importantly, only DNA EP-therapy resulted in a significant decrease in mean viremia titers and in intrahepatic covalently closed circular DNA (cccDNA) levels in chronic DHBV-carrier animals, compared with standard needle pDNA injection (SI). In addition, DNA EP-therapy stimulated in all virus-carriers a humoral response to DHBV preS protein, recognizing a broader range of major antigenic regions, including neutralizing epitopes, compared with SI. DNA EP-therapy led also to significant higher intrahepatic IFN-γ RNA levels in DHBV-carriers compared to other groups, in the absence of adverse effects. We provide the first evidence on DNA EP-therapy benefit in terms of hepadnaviral infection clearance and break of immune tolerance in virus-carriers, supporting its clinical application for chronic hepatitis B.

摘要

本临床前研究调查了电穿孔（EP）递送编码病毒蛋白（包膜、核心）和 IFN-γ 的质粒 DNA（pDNA）在慢性乙型肝炎病毒（DHBV）感染鸭模型中的治疗效果。重要的是，与标准的针状 pDNA 注射（SI）相比，仅 DNA EP 治疗就导致慢性 DHBV 携带者的平均病毒血症滴度和肝内共价闭合环状 DNA（cccDNA）水平显著降低。此外，与 SI 相比，DNA EP 治疗在所有病毒携带者中均刺激了针对 DHBV preS 蛋白的体液反应，识别出更广泛的主要抗原区域，包括中和表位。与其他组相比，DNA EP 治疗还导致 DHBV 携带者的肝内 IFN-γ RNA 水平显著升高，而没有不良反应。我们提供了 DNA EP 治疗在清除肝病毒感染和打破病毒携带者免疫耐受方面的益处的第一个证据，支持其在慢性乙型肝炎中的临床应用。

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In vivo electroporation improves therapeutic potency of a DNA vaccine targeting hepadnaviral proteins.体内电穿孔提高针对肝炎病毒蛋白的 DNA 疫苗的治疗效力。
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