Gao Ying, Zhang Tian-Ying, Yuan Quan, Xia Ning-Shao
a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics , School of Public Health, Xiamen University , Xiamen , China.
b National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science , Xiamen University , Xiamen , China.
Hum Vaccin Immunother. 2017 Aug 3;13(8):1768-1773. doi: 10.1080/21645515.2017.1319021. Epub 2017 May 19.
The currently available drugs to treat hepatitis B virus (HBV) infection include interferons and nucleos(t)ide analogs, 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 described previously 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.
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（酸）类似物，这些药物只能诱导疾病缓解，对于慢性HBV感染（CHB）患者的功能性治愈效果不佳。由于高滴度的循环乙型肝炎表面抗原（HBsAg）可能是耗尽宿主抗HBV免疫反应所必需的，且目前的药物无法显著降低其水平，因此旨在抑制血清乙型肝炎表面抗原（HBsAg）的新抗病毒策略可能有助于恢复病毒特异性免疫反应并促进病毒根除。作为一种替代策略，使用HBsAg特异性抗体的免疫疗法在一些临床前和临床试验研究中已显示出对HBsAg有直接抑制作用。然而，先前描述的大多数HBsAg特异性抗体在CHB患者和模拟持续性HBV感染的动物模型中仅具有非常短期的HBsAg抑制作用。开发用于CHB治疗的抗体介导免疫疗法的临床应用需要具有持久HBsAg清除作用的更强效抗体。我们最近的研究描述了一种新型单克隆抗体E6F6，它靶向HBsAg上的一个独特表位。它可以通过体内Fcγ受体依赖性吞噬作用持久抑制HBsAg和HBV DNA的水平。在这篇评论中，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表位决定的治疗效力。这些见解可能为促进针对持续性病毒感染的治疗性抗体的开发提供一些线索和指导。
