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

• Published in: Vaccine Vol. 36; no. 43; pp. 6383 - 6392
• Main Authors: DeDiego, Marta L., Chiem, Kevin, Topham, David J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 15.10.2018; Elsevier Limited
• Subjects: Amino acid sequence; Amino acids; Amino Acids - genetics; Antibodies; Antibodies, Viral - blood; Antigenic drift; antigenic variation; Antigenic Variation - genetics; Antigenicity; Antigens; Binding sites; Conflicts of interest; Disease; Epidemiological Monitoring; Exo-a-sialidase; Genetic Drift; Glycoproteins; HA protein; HEK293 Cells; Hemagglutinin; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Hemagglutinins; human diseases; Human subjects; Humans; Immune pressure; Immunoglobulins; Infections; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza Vaccines - immunology; Influenza virus; Influenza, Human - prevention & control; Mutation; Neuraminidase; Neuraminidase - genetics; Neuraminidase - immunology; Orthomyxoviridae; Pressure; Proteins; Selection, Genetic; sialidase; Strains (organisms); Surveillance; vaccination; Vaccine efficacy; Vaccines; Viruses; United States > US; California; Influenza virus; Hemagglutinin; Immune pressure; Neuraminidase; Antigenic drift; Antibodies; Vaccines
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2018.09.005

•Under immune pressure, the selection of amino acid changes in the NA protein is more limited than in the HA protein.•Amino acid changes selected in the HA and NA affected protein antigenicity.•Many of the selected amino acid changes were located at the same positions found in viruses circulating.•The approach described may be useful to predict circulating viruses and update vaccine strains. 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.