人单克隆抗体作为慢性乙型肝炎病毒感染的辅助治疗。

StephenW

Front Immunol. 2019 Sep 25;10:2290. doi: 10.3389/fimmu.2019.02290. eCollection 2019.
Human Monoclonal Antibodies as Adjuvant Treatment of Chronic Hepatitis B Virus Infection.
Cerino A1, Mantovani S1, Mele D1, Oliviero B1, Varchetta S1, Mondelli MU1,2.
Author information

1
    S.C. di Malattie Infettive II - Infettivologia e Immunologia, Dipartimento di Scienze Mediche e Malattie Infettive, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
2
    Dipartimento di Medicina Interna e Terapia Medica, Università di Pavia, Pavia, Italy.

Abstract

Despite the availability of an effective prophylactic vaccine leading to sterilizing immunity, hepatitis B virus (HBV) is responsible for chronic liver disease in more than 250 million individuals, potentially leading to cirrhosis and hepatocellular carcinoma. Antiviral drugs able to completely suppress virus replication are indeed available but they are, by and large, unable to eradicate the virus. Several alternative new treatment approaches are currently being developed but none have so far captured the interest of clinicians for possible clinical development. A constant feature of chronic HBV infection is T-cell exhaustion resulting from persistent exposure to high antigen concentrations as shown by the high expression of programmed cell death protein 1 (PD-1) by HBV-specific CD8 T cells. One way of tackling this problem is to develop HBV-specific neutralizing antibodies that would clear excess envelope proteins from the circulation, allowing for nucleos(t)ide analogs or other antiviral drugs now in preclinical and early clinical development to take advantage of a reconstituted adaptive immunity. Several fully human monoclonal antibodies (mAb) have been developed from HBV-vaccinated and subjects convalescent from acute hepatitis B that show different properties and specificities. It is envisaged that such neutralizing mAb may be used as adjuvant treatment to reduce viral protein load, thus rescuing adaptive immunity in an effort to optimize the effect of antiviral drugs.

Copyright © 2019 Cerino, Mantovani, Mele, Oliviero, Varchetta and Mondelli.
KEYWORDS:

B cells; HBV—hepatitis B virus; adaptive immunity; human monoclonal antibody; immune system

PMID:
    31608071
PMCID:
    PMC6773823
DOI:
    10.3389/fimmu.2019.02290

StephenW

前免疫。 2019年9月25日; 10：2290。 doi：10.3389 / fimmu.2019.02290。 eCollection 2019。
人单克隆抗体作为慢性乙型肝炎病毒感染的辅助治疗。
Cerino A1，Mantovani S1，Mele D1，Oliviero B1，Varchetta S1，Mondelli MU1,2。
作者信息

1个
    S.C. di Malattie Infettive II-Infettivologia e Immunologia，Dipartimento di Scienze Mediche e Malattie Infettive，Fondazione IRCCS Policlinico San Matteo，意大利帕维亚。
2
    意大利国际医疗卫生部，意大利帕维亚大学帕维亚分校。

抽象

尽管可以使用有效的预防性疫苗来实现免疫灭菌，但乙肝病毒（HBV）仍可导致超过2.5亿人的慢性肝病，并可能导致肝硬化和肝细胞癌。确实可以使用能够完全抑制病毒复制的抗病毒药物，但总的来说，它们无法根除病毒。当前正在开发几种替代的新治疗方法，但是到目前为止，还没有一种方法吸引了临床医生对可能的临床开发的兴趣。慢性HBV感染的一个恒定特征是持续暴露于高抗原浓度导致T细胞衰竭，如HBV特异性CD8 T细胞高表达程序性细胞死亡蛋白1（PD-1）所示。解决此问题的一种方法是开发可清除循环中多余包膜蛋白的HBV特异性中和抗体，从而使临床前和临床早期开发中的核苷酸（t）ide类似物或其他抗病毒药物能够利用重组的适应性抗体免疫。已经从接种HBV疫苗的急性乙型肝炎患者中开发了几种完全人单克隆抗体（mAb），这些受试者表现出不同的特性和特异性。可以设想，这种中和mAb可以用作减少病毒蛋白负荷的辅助治疗，从而挽救适应性免疫力，以优化抗病毒药物的作用。

版权所有©2019 Cerino，Mantovani，Mele，Oliviero，Varchetta和Mondelli。
关键字：

B细胞； HBV-乙型肝炎病毒；适应性免疫人类单克隆抗体;免疫系统

PMID：
    31608071
PMCID：
    PMC6773823
DOI：
    10.3389 / fimmu.2019.02290