Defining the antibody cross-reactome directed against the influenza virus surface glycoproteins

Nat Immunol. 2017 Apr;18(4):464-473. doi: 10.1038/ni.3684. Epub 2017 Feb 13.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Animals
  • Antibodies, Viral / immunology*
  • Cluster Analysis
  • Cross Reactions / immunology*
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Ferrets
  • Guinea Pigs
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Humans
  • Immunoglobulin G / immunology
  • Influenza A virus / classification
  • Influenza A virus / immunology*
  • Influenza, Human / immunology*
  • Male
  • Mice
  • Middle Aged
  • Neuraminidase / immunology
  • Orthomyxoviridae Infections / immunology*
  • Viral Envelope Proteins / immunology*
  • Viral Proteins / immunology
  • Young Adult


  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immunoglobulin G
  • Viral Envelope Proteins
  • Viral Proteins
  • NA protein, influenza A virus
  • Neuraminidase