title: A common solution to group 2 influenza virus neutralization.
abstract: The discovery and characterization of broadly neutralizing antibodies (bnAbs) against influenza viruses have raised hopes for the development of monoclonal antibody (mAb)-based immunotherapy and the design of universal influenza vaccines. Only one human bnAb (CR8020) specifically recognizing group 2 influenza A viruses has been previously characterized that binds to a highly conserved epitope at the base of the hemagglutinin (HA) stem and has neutralizing activity against H3, H7, and H10 viruses. Here, we report a second group 2 bnAb, CR8043, which was derived from a different germ-line gene encoding a highly divergent amino acid sequence. CR8043 has in vitro neutralizing activity against H3 and H10 viruses and protects mice against challenge with a lethal dose of H3N2 and H7N7 viruses. The crystal structure and EM reconstructions of the CR8043-H3 HA complex revealed that CR8043 binds to a site similar to the CR8020 epitope but uses an alternative angle of approach and a distinct set of interactions. The identification of another antibody against the group 2 stem epitope suggests that this conserved site of vulnerability has great potential for design of therapeutics and vaccines.
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, 2333 CN, Leiden, The Netherlands.
authors: Robert H E
authors: RH
authors: Friesen
authors: Peter S
authors: PS
authors: Lee
authors: Esther J M
authors: EJ
authors: Stoop
authors: Ryan M B
authors: RM
authors: Hoffman
authors: Damian C
authors: DC
authors: Ekiert
authors: Gira
authors: G
authors: Bhabha
authors: Wenli
authors: W
authors: Yu
authors: Jarek
authors: J
authors: Juraszek
authors: Wouter
authors: W
authors: Koudstaal
authors: Mandy
authors: M
authors: Jongeneelen
authors: Hans J W M
authors: HJ
authors: Korse
authors: Carla
authors: C
authors: Ophorst
authors: Els C M
authors: EC
authors: Brinkman-van der Linden
authors: Mark
authors: M
authors: Throsby
authors: Mark J
authors: MJ
authors: Kwakkenbos
authors: Arjen Q
authors: AQ
authors: Bakker
authors: Tim
authors: T
authors: Beaumont
authors: Hergen
authors: H
authors: Spits
authors: Ted
authors: T
authors: Kwaks
authors: Ronald
authors: R
authors: Vogels
authors: Andrew B
authors: AB
authors: Ward
authors: Jaap
authors: J
authors: Goudsmit
authors: Ian A
authors: IA
authors: Wilson
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry; D000911:Antibodies, Monoclonal / Q000737:chemistry; D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000276:immunology*; D000914:Antibodies, Viral / Q000737:chemistry / Q000276:immunology*; D002850:Chromatography, Gel; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry; D006801:Humans; D007156:Immunologic Memory; D009980:Influenza A virus / Q000737:chemistry*; D007252:Influenza Vaccines / Q000737:chemistry / Q000276:immunology; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D008958:Models, Molecular; D008968:Molecular Conformation; D013045:Species Specificity
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines
keywords: X-ray crystallography; antibody recognition; electron microscopy