title: A broadly neutralizing human monoclonal antibody that recognizes a conserved, novel epitope on the globular head of the influenza H1N1 virus hemagglutinin.
abstract: The conserved influenza virus hemagglutinin (HA) stem domain elicits cross-reactive antibodies, but epitopes in the globular head typically elicit strain-specific responses because of the hypervariability of this region. We isolated human monoclonal antibody 5J8, which neutralized a broad spectrum of 20th century H1N1 viruses and the 2009 pandemic H1N1 virus. Fine mapping of the interaction unexpectedly revealed a novel epitope between the receptor-binding pocket and the Ca₂ antigenic site on HA. This antibody exposes a new mechanism underlying broad immunity against H1N1 influenza viruses and identifies a conserved epitope that might be incorporated into engineered H1 virus vaccines.
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Jens C
authors.initials: JC
authors.lastname: Krause
authors.forename: Tshidi
authors.initials: T
authors.lastname: Tsibane
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Tumpey
authors.forename: Chelsey J
authors.initials: CJ
authors.lastname: Huffman
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Basler
authors.forename: James E
authors.initials: JE
authors.lastname: Crowe
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000276:immunology* / Q000627:therapeutic use; D001835:Body Weight; D002460:Cell Line; D003429:Cross Reactions; D004195:Disease Models, Animal; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000188:drug therapy; D012376:Rodent Diseases / Q000188:drug therapy; D017422:Sequence Analysis, DNA; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus