title: A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins.
abstract: The isolation of broadly neutralizing antibodies against influenza A viruses has been a long-sought goal for therapeutic approaches and vaccine design. Using a single-cell culture method for screening large numbers of human plasma cells, we isolated a neutralizing monoclonal antibody that recognized the hemagglutinin (HA) glycoprotein of all 16 subtypes and neutralized both group 1 and group 2 influenza A viruses. Passive transfer of this antibody conferred protection to mice and ferrets. Complexes with HAs from the group 1 H1 and the group 2 H3 subtypes analyzed by x-ray crystallography showed that the antibody bound to a conserved epitope in the F subdomain. This antibody may be used for passive protection and to inform vaccine design because of its broad specificity and neutralization potency.
authors.affiliation: Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland.
authors.forename: Davide
authors.initials: D
authors.lastname: Corti
authors.forename: Jarrod
authors.initials: J
authors.lastname: Voss
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Gamblin
authors.forename: Giosiana
authors.initials: G
authors.lastname: Codoni
authors.forename: Annalisa
authors.initials: A
authors.lastname: Macagno
authors.forename: David
authors.initials: D
authors.lastname: Jarrossay
authors.forename: Sebastien G
authors.initials: SG
authors.lastname: Vachieri
authors.forename: Debora
authors.initials: D
authors.lastname: Pinna
authors.forename: Andrea
authors.initials: A
authors.lastname: Minola
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Vanzetta
authors.forename: Chiara
authors.initials: C
authors.lastname: Silacci
authors.forename: Blanca M
authors.initials: BM
authors.lastname: Fernandez-Rodriguez
authors.forename: Gloria
authors.initials: G
authors.lastname: Agatic
authors.forename: Siro
authors.initials: S
authors.lastname: Bianchi
authors.forename: Isabella
authors.initials: I
authors.lastname: Giacchetto-Sasselli
authors.forename: Lesley
authors.initials: L
authors.lastname: Calder
authors.forename: Federica
authors.initials: F
authors.lastname: Sallusto
authors.forename: Patrick
authors.initials: P
authors.lastname: Collins
authors.forename: Lesley F
authors.initials: LF
authors.lastname: Haire
authors.forename: Nigel
authors.initials: N
authors.lastname: Temperton
authors.forename: Johannes P M
authors.initials: JP
authors.lastname: Langedijk
authors.forename: John J
authors.initials: JJ
authors.lastname: Skehel
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzavecchia
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000302:isolation & purification; D000914:Antibodies, Viral / Q000276:immunology* / Q000302:isolation & purification; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000276:immunology*; D002478:Cells, Cultured; D003429:Cross Reactions; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000276:immunology; D005289:Ferrets; D006031:Glycosylation; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007116:Immunization, Passive; D007135:Immunoglobulin Variable Region / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D009981:Influenza B virus / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D010950:Plasma Cells / Q000276:immunology; D055503:Protein Multimerization; D017433:Protein Structure, Secondary
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007135:Immunoglobulin Variable Region