走向乙型肝炎的功能性治疗：B细胞免疫应答的靶向治疗的原

StephenW

Front Immunol. 2019 Sep 24;10:2308. doi: 10.3389/fimmu.2019.02308. eCollection 2019.
Toward a Functional Cure for Hepatitis B: The Rationale and Challenges for Therapeutic Targeting of the B Cell Immune Response.
Ma Z1, Zhang E2, Gao S1, Xiong Y1, Lu M3.
Author information

1
    Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China.
2
    Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
3
    Institute of Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Abstract

The central role of the cellular immune response in the control and clearance of the hepatitis B virus (HBV) infection has been well-established. The contribution of humoral immunity, including B cell and antibody responses against HBV, has been investigated for a long time but has attracted increasing attention again in recent years. The anti-HBs antibody was first recognized as a marker of protective immunity after the acute resolution of the HBV infection (or vaccination) and is now defined as a biomarker for the functional cure of chronic hepatitis B (CHB). In this way, therapies targeting HBV-specific B cells and the induction of an anti-HBs antibody response are essential elements of a rational strategy to terminate chronic HBV infection. However, a high load of HBsAg in the blood, which has been proposed to induce antigen-specific immune tolerance, represents a major obstacle to curing CHB. Long-term antiviral treatment by nucleoside analogs, by targeting viral translation by siRNA, by inhibiting HBsAg release via nucleic acid polymers, or by neutralizing HBsAg via specific antibodies could potentially reduce the HBsAg load in CHB patients. A combined strategy including a reduction of the HBsAg load via the above treatments and the therapeutic targeting of B cells by vaccination may induce the appearance of anti-HBs antibodies and lead to a functional cure of CHB.

Copyright © 2019 Ma, Zhang, Gao, Xiong and Lu.
KEYWORDS:

B cell response; chronic hepatitis B; functional cure; hepatitis B virus; therapeutic vaccine

PMID:
    31608073
PMCID:
    PMC6769125
DOI:
    10.3389/fimmu.2019.02308

StephenW

前免疫。 2019年9月24日; 10：2308。 doi：10.3389 / fimmu.2019.02308。 eCollection 2019。
走向乙型肝炎的功能性治疗：B细胞免疫应答的靶向治疗的原理和挑战。
马Z1，张E2，高S1，熊Y1，卢M3。
作者信息

1个
武汉大学中南医院感染科，武汉。
2
中国科学院武汉病毒研究所，武汉。
3
德国埃森杜伊斯堡埃森大学埃森大学医院病毒研究所。

抽象

细胞免疫反应在控制和清除乙型肝炎病毒（HBV）感染中的核心作用已得到公认。长期以来研究了体液免疫的作用，包括B细胞和针对HBV的抗体反应。抗HBs抗体在急性解决HBV感染（或接种疫苗）后首先被认为是保护性免疫的标志物，并且现已被定义为慢性肝炎功能治愈的生物标志物顺便说一句，靶向HBV特异性B细胞的疗法和诱导抗HBs抗体反应是终止慢性HBV感染的合理策略的基本要素。然而，已提出诱导抗原特异性免疫耐受的血液中高含量的HBsAg代表了治愈CHB的主要障碍。核苷类似物的长期抗病毒治疗，靶向VER RNA，通过核酸聚合物抑制HBsAg释放，或通过特异性抗体中和HBsAg可能会降低CHB患者的HBsAg负荷。包括通过上述治疗降低HBsAg载量和通过疫苗接种对B细胞进行治疗靶向的联合策略可能会诱导抗HBs抗体的出现并导致CHB的功能性治愈。

版权所有©2019 Ma，Zhang，Gao，Xiong and Lu。
关键字：

B细胞反应；慢性乙型肝炎功能性治疗乙型肝炎病毒；

PMID：
31608073
PMCID：
PMC6769125
DOI：
10.3389 / fimmu.2019.02308