Human monoclonal antibodies targeting the haemagglutinin glycoprotein can neutralize H7N9 influenza virus

被引:36
作者
Chen, Zhe [1 ,2 ]
Wang, Jianmin [1 ,2 ]
Bao, Linlin [3 ,4 ]
Guo, Li [1 ,2 ]
Zhang, Weijia [1 ,2 ]
Xue, Ying [1 ,2 ]
Zhou, Hongli [1 ,2 ]
Xiao, Yan [1 ,2 ]
Wang, Jianwei [1 ,2 ]
Wu, Fan [5 ]
Deng, Ying [6 ]
Qin, Chuan [3 ,4 ]
Jin, Qi [1 ,2 ]
机构
[1] Chinese Acad Med Sci, Inst Pathogen Biol, MOH Key Lab Syst Biol Pathogens, Beijing 100730, Peoples R China
[2] Peking Union Med Coll, Beijing 100021, Peoples R China
[3] Chinese Acad Med Sci, Inst Lab Anim Sci, Beijing 100730, Peoples R China
[4] Minist Hlth, Peking Union Med Collage, Key Lab Human Dis Comparat Med, Comparat Med Ctr, Beijing, Peoples R China
[5] Shanghai Municipal Ctr Dis Control & Prevent, Shanghai, Peoples R China
[6] Beijing Municipal Ctr Dis Control & Prevent, Beijing, Peoples R China
基金
中央高校基本科研业务费专项资金资助;
关键词
RECEPTOR-BINDING; A H7N9; HUMAN INFECTION; H1N1; VIRUS; EMERGENCE; LIBRARIES; EPITOPE; FUSION; CELLS;
D O I
10.1038/ncomms7714
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The recently identified avian-originated influenza H7N9 virus causes severe pulmonary disease and may lead to death in humans. Currently, treatment options for the prevention and control of fatal H7N9 infections in humans remain limited. Here we characterize two human monoclonal antibodies (HuMAbs), HNIgGA6 and HNIgGB5, by screening a Fab antibody phage library derived from patients who recovered from H7N9 infection. Both antibodies exhibit high neutralizing activity against H7N9 virus in cells. Two amino acids in the receptor-binding site, 186V and 226L, are crucial for the binding of these two HuMAbs to viral haemagglutinin antigens. Prophylaxis with HNIgGA6 and HNIgGB5 confers significant immunity against H7N9 virus in a mouse model and significantly reduces the pulmonary virus titre. When administered post infection, therapeutic doses of the HuMAbs also provide robust protection against lethality. These antibodies might represent a potential alternative or adjunct to H7N9 pandemic interventions.
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页数:10
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