针对先天和适应性免疫系统以治疗慢性乙型肝炎病毒感染的

StephenW

Front Immunol. 2020 Feb 7;10:3127. doi: 10.3389/fimmu.2019.03127. eCollection 2019.
Advances in Targeting the Innate and Adaptive Immune Systems to Cure Chronic Hepatitis B Virus Infection.
Meng Z1, Chen Y1, Lu M2.
Author information

1
    Institute of Biomedical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
2
    Institute of Virology, University Hospital Essen, Essen, Germany.

Abstract

"Functional cure" is being pursued as the ultimate endpoint of antiviral treatment in chronic hepatitis B (CHB), which is characterized by loss of HBsAg whether or not anti-HBs antibodies are present. "Functional cure" can be achieved in <10% of CHB patients with currently available therapeutic agents. The dysfunction of specific immune responses to hepatitis B virus (HBV) is considered the major cause of persistent HBV infection. Thus, modulating the host immune system to strengthen specific cellular immune reactions might help eliminate HBV. Strategies are needed to restore/enhance innate immunity and induce HBV-specific adaptive immune responses in a coordinated way. Immune and resident cells express pattern recognition receptors like TLRs and RIG I/MDA5, which play important roles in the induction of innate immunity through sensing of pathogen-associated molecular patterns (PAMPs) and bridging to adaptive immunity for pathogen-specific immune control. TLR/RIG I agonists activate innate immune responses and suppress HBV replication in vitro and in vivo, and are being investigated in clinical trials. On the other hand, HBV-specific immune responses could be induced by therapeutic vaccines, including protein (HBsAg/preS and HBcAg), DNA, and viral vector-based vaccines. More than 50 clinical trials have been performed to assess therapeutic vaccines in CHB treatment, some of which display potential effects. Most recently, using genetic editing technology to generate CAR-T or TCR-T, HBV-specific T cells have been produced to efficiently clear HBV. This review summarizes the progress in basic and clinical research investigating immunomodulatory strategies for curing chronic HBV infection, and critically discusses the rather disappointing results of current clinical trials and future strategies.

Copyright © 2020 Meng, Chen and Lu.
KEYWORDS:

T cell therapy; hepatitis B virus; immunotherapy; innate immunity; therapeutic vaccination

PMID:
    32117201
PMCID:
    PMC7018702
DOI:
    10.3389/fimmu.2019.03127

StephenW

前免疫。 2020年2月7日； 10：3127. Doi：10.3389 / fimmu.2019.03127.eCollection 2019。
针对先天和适应性免疫系统以治疗慢性乙型肝炎病毒感染的进展。
孟Z1，陈Y1，卢M2。
作者信息

1个
湖北医科大学附属太和医院生物医学研究所，十堰
2
德国埃森大学医院病毒学研究所。

抽象

慢性乙型肝炎（CHB）的抗病毒治疗终极目标是“功能治愈”，其特征是无论是否存在抗HBs抗体，HBsAg均会丢失。使用目前可用的治疗剂，在＜10％的CHB患者中可以实现“功能治愈”。对乙型肝炎病毒（HBV）的特异性免疫反应功能障碍被认为是持续性HBV感染的主要原因。因此，调节宿主免疫系统以增强特异性细胞免疫反应可能有助于消除HBV。需要采取策略来恢复/增强先天免疫力，并以协调的方式诱导HBV特异性适应性免疫应答。免疫细胞和常驻细胞表达模式识别受体，如TLR和RIG I / MDA5，它们通过感测病原体相关分子模式（PAMP）并桥接适应性免疫以进行病原体特异性免疫控制，在诱导先天免疫中发挥重要作用。 TLR / RIG I激动剂可在体内和体外激活天然免疫应答并抑制HBV复制，目前正在临床试验中进行研究。另一方面，治疗性疫苗可以诱导HBV特异性免疫反应，包括蛋白质（HBsAg / preS和HBcAg），DNA和基于病毒载体的疫苗。已经进行了50多次临床试验以评估CHB治疗中的治疗性疫苗，其中一些具有潜在的作用。最近，使用基因编辑技术产生CAR-T或TCR-T，已经生产了HBV特异性T细胞来有效清除HBV。这篇综述总结了研究用于治疗慢性HBV感染的免疫调节策略的基础和临床研究的进展，并严格讨论了当前临床试验和未来策略的令人失望的结果。

版权所有©2020 Meng，Chen和Lu。
关键字：

T细胞疗法；乙型肝炎病毒；免疫疗法先天免疫;治疗性疫苗

PMID：
32117201
PMCID：
PMC7018702
DOI：
10.3389 / fimmu.2019.03127

StephenW

https://www.frontiersin.org/articles/10.3389/fimmu.2019.03127/pdf