title: Human monoclonal antibodies targeting the haemagglutinin glycoprotein can neutralize H7N9 influenza virus.
abstract: 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.
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Bao
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Guo
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Weijia
authors.initials: W
authors.lastname: Zhang
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xue
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Zhou
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.affiliation: Beijing Municipal Center for Disease Control and Prevention, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Jin
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology*; D057134:Antibodies, Neutralizing / Q000378:metabolism / Q000494:pharmacology*; D000914:Antibodies, Viral / Q000378:metabolism / Q000494:pharmacology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism*; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus
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