title: Defining the antibody cross-reactome directed against the influenza virus surface glycoproteins.
abstract: Infection with influenza virus induces antibodies to the viral surface glycoproteins hemagglutinin and neuraminidase, and these responses can be broadly protective. To assess the breadth and magnitude of antibody responses, we sequentially infected mice, guinea pigs and ferrets with divergent H1N1 or H3N2 subtypes of influenza virus. We measured antibody responses by ELISA of an extensive panel of recombinant glycoproteins representing the viral diversity in nature. Guinea pigs developed high titers of broadly cross-reactive antibodies; mice and ferrets exhibited narrower humoral responses. Then, we compared antibody responses after infection of humans with influenza virus H1N1 or H3N2 and found markedly broad responses and cogent evidence for 'original antigenic sin'. This work will inform the design of universal vaccines against influenza virus and can guide pandemic-preparedness efforts directed against emerging influenza viruses.
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Raffael
authors.identifier: 0000-0001-5568-5420
authors.initials: R
authors.lastname: Nachbagauer
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Choi
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Ariana
authors.initials: A
authors.lastname: Hirsh
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Margine
authors.affiliation: Division of Bioinformatics, Hokkaido University Research Center for Zoonosis Control, Kitaku, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Iida
authors.affiliation: Departamento de Enfermedades Infecciosas e Inmunología Pediátrica, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Aldo
authors.initials: A
authors.lastname: Barrera
authors.affiliation: Departamento de Enfermedades Infecciosas e Inmunología Pediátrica, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Marcela
authors.initials: M
authors.lastname: Ferres
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Randy A
authors.identifier: 0000-0003-4008-503X
authors.initials: RA
authors.lastname: Albrecht
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Bouvier
authors.affiliation: Division of Bioinformatics, Hokkaido University Research Center for Zoonosis Control, Kitaku, Japan.
authors.forename: Kimihito
authors.initials: K
authors.lastname: Ito
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Departamento de Enfermedades Infecciosas e Inmunología Pediátrica, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.|Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Medina
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Palese
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Florian
authors.initials: F
authors.lastname: Krammer
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D016000:Cluster Analysis; D003429:Cross Reactions / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005289:Ferrets; D006168:Guinea Pigs; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D009980:Influenza A virus / Q000145:classification / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009439:Neuraminidase / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C487630:NA protein, influenza A virus; D009439:Neuraminidase