Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection.
Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection.
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DOI：
10.1016/j.cell.2015.12.022
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发表时间：
2016-01-28
期刊：
影响因子：
64.5
通讯作者：
Crowe JE Jr
中科院分区：
文献类型：
--
作者：
Flyak AI;Shen X;Murin CD;Turner HL;David JA;Fusco ML;Lampley R;Kose N;Ilinykh PA;Kuzmina N;Branchizio A;King H;Brown L;Bryan C;Davidson E;Doranz BJ;Slaughter JC;Sapparapu G;Klages C;Ksiazek TG;Saphire EO;Ward AB;Bukreyev A;Crowe JE Jr
最近的研究表明，针对埃博拉病毒的抗体介导的保护可能是可实现的，但关于抗体是否可以赋予针对属于不同埃博拉病毒物种的病毒的交叉反应性保护，例如埃博拉病毒（EBOV），苏丹病毒（SUDV）和本迪布焦病毒（BDBV），知之甚少。我们使用2007年乌干达BDBV疫情幸存者的外周血B细胞分离了大量针对BDBV糖蛋白（GP）的人单克隆抗体（mAb）。我们确定，大部分对BDBV具有强效中和活性的mAb与聚糖帽结合，并识别该主要抗原位点内的不同表位。我们鉴定了几种中和多种埃博拉病毒（包括SUDV）的聚糖帽特异性mAb，以及完全保护豚鼠免受异源EBOV致死性攻击的交叉反应性mAb。我们的研究结果为开发有效对抗多种埃博拉病毒感染的单一抗体治疗提供了路线图。
Recent studies have suggested that antibody-mediated protection against the Ebolaviruses may be achievable, but little is known about whether or not antibodies can confer cross-reactive protection against viruses belonging to diverse Ebolavirus species, such as Ebola virus (EBOV), Sudan virus (SUDV) and Bundibugyo virus (BDBV). We isolated a large panel of human monoclonal antibodies (mAbs) against BDBV glycoprotein (GP) using peripheral blood B cells from survivors of the 2007 BDBV outbreak in Uganda. We determined that a large proportion of mAbs with potent neutralizing activity against BDBV bind to the glycan cap and recognize diverse epitopes within this major antigenic site. We identified several glycan cap-specific mAbs that neutralized multiple ebolaviruses including SUDV, and a cross-reactive mAb that completely protected guinea pigs from the lethal challenge with heterologous EBOV. Our results provide a roadmap to develop a single antibody-based treatment effective against multiple Ebolavirus infections.