抗体介导的慢性乙型肝炎病毒感染免疫治疗

StephenW

Hum Vaccin Immunother. 2017 May 19:0. doi: 10.1080/21645515.2017.1319021. [Epub ahead of print]
Antibody-mediated immunotherapy against chronic hepatitis B virus infection.
Gao Y1,2, Zhang TY1,2, Yuan Q1,2, Xia NS1,2.
Author information

1    a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University , Xiamen 361102 , China.
2    b National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University , Xiamen 361102 , China.

Abstract

The currently available drugs to treat hepatitis B virus (HBV) infection include interferons and nucleos(t)ide analogues, which can only induce disease remission and are inefficient for the functional cure of patients with chronic HBV infection (CHB). Since high titers of circulating hepatitis B surface antigen (HBsAg) may be essential to exhaust the host anti-HBV immune response and they cannot be significantly reduced by current drugs, new antiviral strategies aiming to suppress serum hepatitis B surface antigen (HBsAg) could help restore virus-specific immune responses and promote the eradication of the virus. As an alternative strategy, immunotherapy with HBsAg-specific antibodies has shown some direct HBsAg suppression effects in several preclinical and clinical trial studies. However, most previously described HBsAg-specific antibodies only had very short-term HBsAg suppression effects in CHB patients and animal models mimicking persistent HBV infection. More-potent antibodies with long-lasting HBsAg clearance effects are required for the development of the clinical application of antibody-mediated immunotherapy for CHB treatment. Our recent study described a novel mAb E6F6 that targets a unique epitope on HBsAg. It could durably suppress the levels of HBsAg and HBV DNA via Fcγ receptor-dependent phagocytosis in vivo. In this commentary, we summarize the current research progress, including the therapeutic roles and mechanisms of antibody-mediated HBV clearance as well as the epitope-determined therapeutic potency of the antibody. These insights may provide some clues and guidance to facilitate the development of therapeutic antibodies against persistent viral infection.
KEYWORDS:

Antibody-mediated immunotherapy; FcγR-mediated phagocytosis; chronic hepatitis B virus infection; monoclonal antibodies; persistent viral infection

PMID:
    28521640
DOI:
    10.1080/21645515.2017.1319021

StephenW

Hum Vaccin Immunother。 2017年5月19日：0。 doi：10.1080 / 21645515.2017.1319021。 [提前印刷]
抗体介导的慢性乙型肝炎病毒感染免疫治疗。
高Y1,2张TY 1,2，元Q1,2，夏NS1,2。
作者信息

1厦门大学公共卫生学院分子疫苗与分子诊断国家重点实验室，厦门361102。
2 b厦门大学生命科学学院传染病诊断与疫苗开发研究所，厦门361102。

抽象

目前可用于治疗乙型肝炎病毒（HBV）感染的药物包括干扰素和核苷类似物，其仅能诱导疾病缓解，并且对于慢性HBV感染（CHB）患者的功能治疗是低效的。由于循环乙型肝炎表面抗原（HBsAg）的高滴度对于排除宿主抗HBV免疫应答是至关重要的，并且它们不能被目前的药物显着降低，旨在抑制血清乙型肝炎表面抗原（HBsAg）的新的抗病毒策略可以帮助恢复病毒特异性免疫应答并促进根除病毒。作为替代策略，具有HBsAg特异性抗体的免疫治疗已经在几项临床前和临床试验研究中显示出一些直接的HBsAg抑制作用。然而，大多数以前描述的HBsAg特异性抗体仅在CHB患者和模拟持续性HBV感染的动物模型中具有非常短期的HBsAg抑制作用。需要具有持久的HBsAg清除效应的更有效的抗体用于开发用于CHB治疗的抗体介导的免疫治疗的临床应用。我们最近的研究描述了一种靶向HBsAg独特表位的新型单克隆抗体E6F6。可以通过体内Fcγ受体依赖的吞噬作用持续抑制HBsAg和HBV DNA的水平。在本评论中，我们总结了当前的研究进展，包括抗体介导的HBV清除的治疗作用和机制以及抗体的表位确定的治疗效力。这些见解可能提供一些线索和指导，以促进针对持续性病毒感染的治疗性抗体的开发。
关键词：

抗体介导的免疫治疗; FcγR介导的吞噬作用;慢性乙型肝炎病毒感染;单克隆抗体持续性病毒感染

结论：
    28521640
DOI：
    10.1080 / 21645515.2017.1319021

灵魂不屈

感谢分享！

gdxsy

Abstract
摘要