title: A highly conserved neutralizing epitope on group 2 influenza A viruses.
abstract: Current flu vaccines provide only limited coverage against seasonal strains of influenza viruses. The identification of V(H)1-69 antibodies that broadly neutralize almost all influenza A group 1 viruses constituted a breakthrough in the influenza field. Here, we report the isolation and characterization of a human monoclonal antibody CR8020 with broad neutralizing activity against most group 2 viruses, including H3N2 and H7N7, which cause severe human infection. The crystal structure of Fab CR8020 with the 1968 pandemic H3 hemagglutinin (HA) reveals a highly conserved epitope in the HA stalk distinct from the epitope recognized by the V(H)1-69 group 1 antibodies. Thus, a cocktail of two antibodies may be sufficient to neutralize most influenza A subtypes and, hence, enable development of a universal flu vaccine and broad-spectrum antibody therapies.
authors: Department of Molecular Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Damian C
authors: DC
authors: Ekiert
authors: Robert H E
authors: RH
authors: Friesen
authors: Gira
authors: G
authors: Bhabha
authors: Ted
authors: T
authors: Kwaks
authors: Mandy
authors: M
authors: Jongeneelen
authors: Wenli
authors: W
authors: Yu
authors: Carla
authors: C
authors: Ophorst
authors: Freek
authors: F
authors: Cox
authors: Hans J W M
authors: HJ
authors: Korse
authors: Boerries
authors: B
authors: Brandenburg
authors: Ronald
authors: R
authors: Vogels
authors: Just P J
authors: JP
authors: Brakenhoff
authors: Ronald
authors: R
authors: Kompier
authors: Martin H
authors: MH
authors: Koldijk
authors: Lisette A H M
authors: LA
authors: Cornelissen
authors: Leo L M
authors: LL
authors: Poon
authors: Malik
authors: M
authors: Peiris
authors: Wouter
authors: W
authors: Koudstaal
authors: Ian A
authors: IA
authors: Wilson
authors: Jaap
authors: J
authors: Goudsmit
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000302:isolation & purification; D000914:Antibodies, Viral / Q000276:immunology* / Q000302:isolation & purification; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001666:Binding Sites, Antibody; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D053126:Influenza A Virus, H7N7 Subtype / Q000235:genetics / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D011487:Protein Conformation
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines