title: A novel neutralizing antibody against diverse clades of H5N1 influenza virus and its mutants capable of airborne transmission.
abstract: Highly pathogenic avian influenza A virus H5N1 continues to spread among poultry and has frequently broken the species barrier to humans. Recent studies have shown that a laboratory-mutated or reassortant H5N1 virus bearing hemagglutinin (HA) with as few as four or five mutations was capable of transmitting more efficiently via respiratory droplets between ferrets, posing a serious threat to public health and underscoring the priority of effective vaccines and therapeutics. In this study, we identified a novel monoclonal antibody (mAb) named HAb21, that has a broadly neutralizing activity against all tested strains of H5N1 covering clades 0, 1, 2.2, 2.3.4, and 2.3.2.1. Importantly, HAb21 efficiently neutralized diverse H5N1 variants with single or combination forms of mutations capable of airborne transmission. We demonstrated that HAb21 blocked viral entry during the receptor-binding step by targeting a previously uncharacterized epitope at the tip of the HA head. This novel epitope closely neighbors the receptor-binding site (RBS) and the interface of HA trimer and is highly conserved among divergent H5N1 strains. Our studies provide a new tool for use either for therapeutic purposes or as a basis of vaccine development.
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Ruiping
authors.initials: R
authors.lastname: Wu
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Microbiology, University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Ho-Chuen
authors.initials: HC
authors.lastname: Leung
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Cao
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Zonglin
authors.initials: Z
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Yusen
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Microbiology, University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Bo-Jian
authors.initials: BJ
authors.lastname: Zheng
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: yhe@ipb.pumc.edu.cn.
authors.forename: Yuxian
authors.initials: Y
authors.lastname: He
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004195:Disease Models, Animal; D004285:Dogs; D005289:Ferrets; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology*; D007251:Influenza, Human; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000635:transmission / Q000821:virology; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000998:Antiviral Agents
keywords: Epitope; H5N1; Influenza A virus; Mutation; Neutralizing antibody