恢复，释放或替代慢性乙型肝炎的适应性免疫

StephenW

Restoring, releasing or replacing adaptive immunity in chronic hepatitis B

    Mala K. Maini

    & Alice R. Burton

Nature Reviews Gastroenterology & Hepatology volume 16, pages662–675 (2019) | Download Citation
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Abstract

Multiple new therapeutic approaches are currently being developed to achieve sustained, off-treatment suppression of HBV, a persistent hepatotropic infection that kills ~2,000 people a day. A fundamental therapeutic goal is the restoration of robust HBV-specific adaptive immune responses that are able to maintain prolonged immunosurveillance of residual infection. Here, we provide insight into key components of successful T cell and B cell responses to HBV, discussing the importance of different specificities and effector functions, local intrahepatic immunity and pathogenic potential. We focus on the parallels and interactions between T cell and B cell responses, highlighting emerging areas for future investigation. We review the potential for different immunotherapies in development to restore or release endogenous adaptive immunity by direct or indirect approaches, including limitations and risks. Finally, we consider an alternative HBV treatment strategy of replacing failed endogenous immunity with infusions of highly targeted T cells or antibodies.
Key points

    Unprecedented opportunities exist to develop immunotherapeutic approaches that complement novel antiviral agents to achieve sustained control of residual HBV in chronic HBV infection (CHB).

    Adaptive immune responses (HBV-specific T cells and B cells) provide precise antiviral targeting of HBV-infected hepatocytes and/or virions, but also have the potential to trigger tissue damage.

    HBV-specific T cell and B cell responses should be examined in parallel to consider their crosstalk, complementary effector mechanisms and their features of dysfunction in CHB.

    Inadequate HBV-specific T cell and B cell responses might be restored by immunogenic therapeutic vaccines and might be released from inhibition by antigen load reduction or more specific immunomodulation such as checkpoint inhibition.

    Alternatively, the failed endogenous adaptive response can be replaced with targeted exogenous T cell- or B cell-derived HBV-specific effectors.

StephenW

恢复，释放或替代慢性乙型肝炎的适应性免疫

    马拉·缅因

    和爱丽丝·伯顿（Alice R.Burton）

自然评论胃肠病学和肝脏病学第16卷，第662–675页（2019）|下载引文
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抽象

目前正在开发多种新的治疗方法，以实现持续的，非治疗性的HBV抑制，HBV是一种持续的肝病感染，每天可杀死约2,000人。一个基本的治疗目标是恢复强大的HBV特异性适应性免疫反应，该反应能够维持残留感染的长期免疫监测。在这里，我们提供了成功的T细胞和B细胞对HBV应答的关键组成部分的见识，并讨论了不同特异性和效应子功能，局部肝内免疫和致病性潜力的重要性。我们专注于T细胞和B细胞反应之间的相似性和相互作用，重点介绍了需要进一步研究的新兴领域。我们通过直接或间接方法（包括局限性和风险性）回顾了开发中不同免疫疗法恢复或释放内源性适应性免疫的潜力。最后，我们考虑了另一种HBV治疗策略，即通过注入高度靶向的T细胞或抗体来替代失败的内源性免疫。
关键点

    存在前所未有的机会来开发免疫治疗方法，以补充新型抗病毒药物，以实现对慢性HBV感染（CHB）中残留HBV的持续控制。

    适应性免疫应答（HBV特异性T细胞和B细胞）可对HBV感染的肝细胞和/或病毒粒子提供精确的抗病毒靶向，但也有可能触发组织损伤。

    应当并行检查HBV特异性T细胞和B细胞反应，以考虑其串扰，互补效应器机制及其在CHB中功能障碍的特征。

    免疫原性治疗性疫苗可能会恢复不足的HBV特异性T细胞和B细胞反应，并可能因抗原载量降低或更特异性的免疫调节（如检查点抑制）而从抑制作用中释放出来。

    或者，可以用靶向的外源性T细胞或B细胞衍生的HBV特异性效应物代替失败的内源性适应性反应。