title: Identification of Hemagglutinin Residues Responsible for H3N2 Antigenic Drift during the 2014-2015 Influenza Season.
abstract: Influenza vaccines must be updated regularly because influenza viruses continuously acquire mutations in antibody binding sites of hemagglutinin (HA). The majority of H3N2 strains circulating in the Northern Hemisphere during the 2014-2015 season are antigenically mismatched to the A/Texas/50/2012 H3N2 vaccine strain. Recent H3N2 strains possess several new HA mutations, and it is unknown which of these mutations contribute to the 2014-2015 vaccine mismatch. Here, we use reverse genetics to demonstrate that mutations in HA antigenic site B are primarily responsible for the current mismatch. Sera isolated from vaccinated humans and infected ferrets and sheep had reduced hemagglutination inhibition and in vitro neutralization titers against reverse-genetics-derived viruses possessing mutations in the HA antigenic site B. These data provide an antigenic explanation for the low influenza vaccine efficacy observed during the 2014-2015 influenza season. Furthermore, our data support the World Health Organization's decision to update the H3N2 component of future vaccine formulations.
authors.affiliation: Wistar Institute, Philadelphia, PA 19104, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Chambers
authors.affiliation: Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Kaela
authors.initials: K
authors.lastname: Parkhouse
authors.affiliation: Department of Vaccine and Viral Immunity, Vaccine and Gene Therapy Institute of Florida, Port St. Lucie, FL 34987, USA.
authors.forename: Ted M
authors.initials: TM
authors.lastname: Ross
authors.affiliation: Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Alby
authors.affiliation: Wistar Institute, Philadelphia, PA 19104, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: shensley@wistar.org.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Hensley
mesh_terms: D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000235:genetics* / Q000276:immunology; D001666:Binding Sites, Antibody; D004196:Disease Outbreaks; D040961:Genetic Drift; D006388:Hemagglutinins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: D000956:Antigens, Viral; D006388:Hemagglutinins