Potent neutralizing monoclonal antibodies against Ebola virus infection

针对埃博拉病毒感染的强效中和单克隆抗体

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作者:Qi Zhang, Miao Gui, Xuefeng Niu, Shihua He, Ruoke Wang, Yupeng Feng, Andrea Kroeker, Yanan Zuo, Hua Wang, Ying Wang, Jiade Li, Chufang Li, Yi Shi, Xuanling Shi, George F Gao, Ye Xiang, Xiangguo Qiu, Ling Chen, Linqi Zhang

Abstract

Ebola virus infections cause a deadly hemorrhagic disease for which no vaccines or therapeutics has received regulatory approval. Here we show isolation of three (Q206, Q314 and Q411) neutralizing monoclonal antibodies (mAbs) against the surface glycoprotein (GP) of Ebola virus identified in West Africa in 2014 through sequential immunization of Chinese rhesus macaques and antigen-specific single B cell sorting. These mAbs demonstrated potent neutralizing activities against both pseudo and live Ebola virus independent of complement. Biochemical, single particle EM, and mutagenesis analysis suggested Q206 and Q411 recognized novel epitopes in the head while Q314 targeted the glycan cap in the GP1 subunit. Q206 and Q411 appeared to influence GP binding to its receptor NPC1. Treatment with these mAbs provided partial but significant protection against disease in a mouse model of Ebola virus infection. These novel mAbs could serve as promising candidates for prophylactic and therapeutic interventions against Ebola virus infection.

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