免疫调节治疗慢性乙型肝炎，发现病毒经过五十多年的当前

StephenW

Antiviral Res. 2015 Oct 14. pii: S0166-3542(15)30010-3. doi: 10.1016/j.antiviral.2015.10.009. [Epub ahead of print]
Current status of immunomodulatory therapy in chronic hepatitis B, fifty years after discovery of the virus: search for the "magic bullet" to kill cccDNA.Zhang E1, Kosinska A2, Lu M3, Yan H1, Roggendorf M4.
Author information

• 1Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
• 2Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany.
• 3Institute for Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
• 4Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany; Institute for Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany. Electronic address: [email protected].
  

AbstractChronic hepatitis B (CHB) is currently treated with IFN-α and nucleos(t)ide analogues, which have many clinical benefits, but there is no ultimate cure. The major problem consists in the persistence of cccDNA in infected hepatocytes. Because no antiviral drug has been evaluated which significantly reduces copies of cccDNA, cytolytic and noncytolytic approaches are needed. Effective virus-specific T- and B-cell responses remain crucial in eliminating cccDNA-carrying hepatocytes and for the long-term control of HBV infection. Reduction of viremia by antiviral drugs provides a window for reconstitution of an HBV-specific immune response. Preclinical studies in mice and woodchucks have shown that immunostimulatory strategies, such as prime-boost vaccination and PD-1 blockade, can boost a weak virus-specific T cell response and lead to effective control of HBV infection. Based on data obtained in our preclinical studies, the combination of antiviral drugs and immunomodulators may control HBV viremia during a patient's drug-off period. In this article, we review current immune-modulatory approaches for the treatment of chronic hepatitis B and the elimination of cccDNA in preclinical models. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis".
Copyright © 2015. Published by Elsevier B.V.


KEYWORDS: Hepatitis B virus; Immunomodulators; Immunotherapy; Prime-boost immunization; cccDNA

PMID:26476376 [PubMed - as supplied by publisher]

StephenW

抗病毒水库。 2015年十月14 PII：S0166-3542（15）30010-3。 DOI：10.1016 / j.antiviral.2015.10.009。 [打印EPUB提前]
免疫调节治疗慢性乙型肝炎，发现病毒经过五十多年的当前状态：寻找“灵丹妙药”杀cccDNA的。
张E1，Kosinska A2，吕M3，闫H1，Roggendorf先生M4。
作者信息

    1Mucosal免疫研究小组，病毒学国家重点实验室，武汉病毒研究所，中国院士，武汉，湖北，中国。
    2中国科学院病毒学，慕尼黑工业大学/亥姆霍兹慕尼黑中心，德国慕尼黑。
    3Institute病毒学，杜伊斯堡 - 埃森大学大学医院埃森，德国埃森。
    4Institute病毒学，慕尼黑工业大学/亥姆霍兹慕尼黑中心，慕尼黑，德国;杜伊斯堡 - 埃森，德国埃森大学研究所病毒学，埃森大学医院。电子地址：[email protected]。

抽象的

慢性乙型肝炎（CHB）当前与IFN-α和核苷（酸）类似物，其中有许多临床益处治疗，但目前还没有最终的固化。主要的问题在于cccDNA的在感染的肝细胞持续存在。因为没有抗病毒药物已被评估哪些显著降低cccDNA的副本，需要细胞溶解和noncytolytic方法。有效的病毒特异性T细胞和B细胞反应保持在消除cccDNA的承载肝细胞和用于长期控制HBV感染的关键。由抗病毒药物还原病毒血症提供的HBV特异性免疫应答重建的窗口。在老鼠和旱獭临床前研究表明，免疫策略，如初免 - 加强疫苗接种和PD-1阻断，可以提高弱病毒特异性T细胞反应，并导致有效控制乙肝病毒感染。根据我们的临床前研究获得的数据，抗病毒药物和免疫调节的组合可能会在病人的药物帐期控制乙肝病毒血症。在这篇文章中，我们回顾了当前的免疫调节方法治疗慢性乙型肝炎的治疗和消除的cccDNA的临床前模型。本文中形成抗病毒研究的专题讨论会的一部分，对“一个未完成的故事：从澳大利亚抗原的发现到新的治疗疗法的发展为肝炎”。

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