title: A human antibody recognizing a conserved epitope of H5 hemagglutinin broadly neutralizes highly pathogenic avian influenza H5N1 viruses.
abstract: Influenza A virus infection is a persistent threat to public health worldwide due to its ability to evade immune surveillance through rapid genetic drift and shift. Current vaccines against influenza A virus provide immunity to viral isolates that are similar to vaccine strains. High-affinity neutralizing antibodies against conserved epitopes could provide immunity to diverse influenza virus strains and protection against future pandemic viruses. In this study, by using a highly sensitive H5N1 pseudotype-based neutralization assay to screen human monoclonal antibodies produced by memory B cells from an H5N1-infected individual and molecular cloning techniques, we developed three fully human monoclonal antibodies. Among them, antibody 65C6 exhibited potent neutralization activity against all H5 clades and subclades except for subclade 7.2 and prophylactic and therapeutic efficacy against highly pathogenic avian influenza H5N1 viruses in mice. Studies on hemagglutinin (HA)-antibody complexes by electron microscopy and epitope mapping indicate that antibody 65C6 binds to a conformational epitope comprising amino acid residues at positions 118, 121, 161, 164, and 167 (according to mature H5 numbering) on the tip of the membrane-distal globular domain of HA. Thus, we conclude that antibody 65C6 recognizes a neutralization epitope in the globular head of HA that is conserved among almost all divergent H5N1 influenza stains.
authors.affiliation: Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences,Shanghai, China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Hu
authors.forename: Jarrod
authors.initials: J
authors.lastname: Voss
authors.forename: Guoliang
authors.initials: G
authors.lastname: Zhang
authors.forename: Philippi
authors.initials: P
authors.lastname: Buchy
authors.forename: Teng
authors.initials: T
authors.lastname: Zuo
authors.forename: Lulan
authors.initials: L
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Fan
authors.initials: F
authors.lastname: Zhou
authors.forename: Guiqing
authors.initials: G
authors.lastname: Wang
authors.forename: Cheguo
authors.initials: C
authors.lastname: Tsai
authors.forename: Lesley
authors.initials: L
authors.lastname: Calder
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Gamblin
authors.forename: Linqi
authors.initials: L
authors.lastname: Zhang
authors.forename: Vincent
authors.initials: V
authors.lastname: Deubel
authors.forename: Boping
authors.initials: B
authors.lastname: Zhou
authors.forename: John J
authors.initials: JJ
authors.lastname: Skehel
authors.forename: Paul
authors.initials: P
authors.lastname: Zhou
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D017124:Conserved Sequence; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D009980:Influenza A virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009500:Neutralization Tests
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; C109963:hemagglutinin, avian influenza A virus