Non-neutralizing Antibodies from a Marburg Infection Survivor Mediate Protection by Fc-Effector Functions and by Enhancing Efficacy of Other Antibodies
Non-neutralizing Antibodies from a Marburg Infection Survivor Mediate Protection by Fc-Effector Functions and by Enhancing Efficacy of Other Antibodies
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DOI：
10.1016/j.chom.2020.03.025
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发表时间：
2020-06-10
影响因子：
30.3
通讯作者：
Bukreyev, Alexander
中科院分区：
文献类型：
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作者：
Ilinykh, Philipp A.;Huang, Kai;Bukreyev, Alexander
马尔堡病毒（MARV）和埃博拉病毒（EBOV）属于丝状病毒科。MARV在人类中引起严重疾病，具有高死亡率。我们先前从先前自然获得的MARV感染的人类幸存者的B细胞中分离出一大组单克隆抗体（mAb）。在这里，我们表征了这些mAb的功能特性，并鉴定了靶向MARV GP的粘蛋白样结构域（MLD）的糖蛋白（GP）2部分（称为翼区）的非中和mAb。一种靶向GP2翼区的mAb MR228在感染MARV的小鼠和豚鼠中显示出治疗保护作用。这种保护作用是由MR228的Fc片段功能介导的。另一种GP2翼区特异性非中和mAb MR 235与MARV GP的结合增加了中和mAb的受体结合位点（RBS）中表位的可及性，导致这些mAb的病毒中和增强。这些发现强调了非中和mAb在自然人MARV感染期间的重要作用。
Marburg virus (MARV) and Ebola virus (EBOV) belong to the family Filoviridae. MARV causes severe disease in humans with high fatality. We previously isolated a large panel of monoclonal antibodies (mAbs) from B cells of a human survivor with previous naturally acquired MARV infection. Here, we characterized functional properties of these mAbs and identified non-neutralizing mAbs targeting the glycoprotein (GP) 2 portion of the mucin-like domain (MLD) of MARV GP, termed the wing region. One mAb targeting the GP2 wing, MR228, showed therapeutic protection in mice and guinea pigs infected with MARV. The protection was mediated by the Fc fragment functions of MR228. Binding of another GP2 wing-specific non-neutralizing mAb, MR235, to MARV GP increased accessibility of epitopes in the receptor-binding site (RBS) for neutralizing mAbs, resulting in enhanced virus neutralization by these mAbs. These findings highlight an important role for non-neutralizing mAbs during natural human MARV infection.