Directed selection of amino acid changes in the influenza hemagglutinin and neuraminidase affecting protein antigenicity

Vaccine. 2018 Oct 15;36(43):6383-6392. doi: 10.1016/j.vaccine.2018.09.005. Epub 2018 Sep 14.

Abstract

Influenza virus hemagglutinin (HA) and neuraminidase (NA) proteins elicit protective antibody responses and therefore, are used as targets for vaccination, especially the HA protein. However, these proteins are subject to antigenic drift, decreasing vaccine efficacy, and few to no studies have analyzed antigenic variability of these proteins by growing the viruses under immune pressure provided by human sera. In this work, we show that after growing different influenza virus strains under immune pressure, the selection of amino acid changes in the NA protein is much more limited than the selection in the HA protein, suggesting that the NA protein could remain more conserved under immune pressure. Interestingly, all the mutations in the HA and NA proteins affected protein antigenicity, and many of the selected amino acid changes were located at the same positions found in viruses circulating. These studies could help to inform HA and NA protein residues targeted by antibody responses after virus infection in humans and are very relevant to update the strains used for influenza virus vaccination each year and to improve the currently available vaccines.

Keywords: Antibodies; Antigenic drift; Hemagglutinin; Immune pressure; Influenza virus; Neuraminidase; Vaccines.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acids / genetics*
  • Antibodies, Viral / blood
  • Antigenic Variation / genetics*
  • Epidemiological Monitoring
  • Genetic Drift*
  • HEK293 Cells
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics*
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Humans
  • Influenza A Virus, H1N1 Subtype
  • Influenza A Virus, H3N2 Subtype
  • Influenza Vaccines / immunology
  • Influenza, Human / prevention & control
  • Neuraminidase / genetics*
  • Neuraminidase / immunology
  • Selection, Genetic

Substances

  • Amino Acids
  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Neuraminidase