Zhang Qi, Gui Miao, Niu Xuefeng, He Shihua, Wang Ruoke, Feng Yupeng, Kroeker Andrea, Zuo Yanan, Wang Hua, Wang Ying, Li Jiade, Li Chufang, Shi Yi, Shi Xuanling, Gao George F, Xiang Ye, Qiu Xiangguo, Chen Ling, Zhang Linqi
Comprehensive AIDS Research Center, and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
Beijing Advanced Innovation Center for Structure Biology, and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
Sci Rep. 2016 May 16;6:25856. doi: 10.1038/srep25856.
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.
埃博拉病毒感染会引发一种致命的出血热疾病，目前尚无疫苗或治疗方法获得监管批准。在此，我们展示了通过对中国恒河猴进行连续免疫并进行抗原特异性单B细胞分选，于2014年在西非分离出三种针对埃博拉病毒表面糖蛋白（GP）的中和单克隆抗体（mAb）（Q206、Q314和Q411）。这些单克隆抗体对假型和活埃博拉病毒均表现出强大的中和活性，且不依赖补体。生化、单颗粒电子显微镜和诱变分析表明，Q206和Q411识别头部的新表位，而Q314靶向GP1亚基中的聚糖帽。Q206和Q411似乎影响GP与其受体NPC1的结合。在埃博拉病毒感染的小鼠模型中，用这些单克隆抗体治疗可提供部分但显著的疾病保护。这些新型单克隆抗体有望成为预防和治疗埃博拉病毒感染的候选药物。
