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Non-neutralizing Antibodies from a Marburg Infection Survivor Mediate Protection by Fc-Effector Functions and by Enhancing Efficacy of Other Antibodies.
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2020-04-21 , DOI: 10.1016/j.chom.2020.03.025
Philipp A Ilinykh 1 , Kai Huang 1 , Rodrigo I Santos 1 , Pavlo Gilchuk 2 , Bronwyn M Gunn 3 , Marcus M Karim 3 , Jenny Liang 4 , Mallorie E Fouch 4 , Edgar Davidson 4 , Diptiben V Parekh 5 , James B Kimble 1 , Colette A Pietzsch 1 , Michelle Meyer 1 , Natalia A Kuzmina 1 , Larry Zeitlin 6 , Erica Ollmann Saphire 7 , Galit Alter 3 , James E Crowe 8 , Alexander Bukreyev 9
Affiliation  

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.



中文翻译:

马尔堡感染幸存者的非中和抗体通过Fc效应子功能和增强其他抗体的功效介导保护作用。

马尔堡病毒(MARV)和埃博拉病毒(EBOV)属于丝虫科。MARV在高死亡率的人类中引起严重疾病。我们先前从以前自然获得性MARV感染的人类幸存者的B细胞中分离出一大批单克隆抗体(mAb)。在这里,我们表征了这些mAb的功能特性,并确定了靶向MARV GP粘蛋白样结构域(MLD)糖蛋白(GP)2部分(称为翼区)的非中和mAb。一种针对GP2机翼的单抗MR228在感染MARV的小鼠和豚鼠中显示出治疗保护作用。该保护由MR228的Fc片段功能介导。另一个GP2机翼特异性非中和单克隆抗体MR235与MARV GP的结合增加了受体结合位点(RBS)中表位对中和mAb的可及性,导致这些mAb增强了对病毒的中和作用。

更新日期:2020-04-21
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