Epitopes described in "Immunodominance of antigenic site B over site A of hemagglutinin of recent H3N2 influenza viruses."

Reference
Article Authors:Lyubov Popova; Kenneth Smith; Ann H West; Patrick C Wilson; Judith A James; Linda F Thompson; Gillian M Air
Article Title:Immunodominance of antigenic site B over site A of hemagglutinin of recent H3N2 influenza viruses.
Reference Detail
Reference ID:1025450
Abstract:H3N2 influenza viruses have now circulated in the human population for 43 years since the pandemic of 1968, accumulating sequence changes in the hemagglutinin (HA) and neuraminidase (NA) that are believed to be predominantly due to selection for escape from antibodies. Examination of mutations that persist and accumulate led to identification of antigenically significant mutations that are contained in five antigenic sites (A-E) mapped on to the H3 HA. In early H3N2 isolates, antigenic site A appeared to be dominant while in the 1990s site B seemed more important. To obtain experimental evidence for dominance of antigenic sites on modern H3 HAs, we have measured antibodies in plasma of human subjects who received the 2006-07 trivalent subunit influenza vaccine (H3 component A/Wisconsin/67/05) or the 2008-09 formulation (H3 component A/Uruguay/716/07). Plasmas were tested against expressed HA of Wisconsin-like influenza A/Oklahoma/309/06 and site-directed mutants in antigenic site A (NNES121-124ITEG, N126T, N133D, TSSS135-138GSNA, K140I, RSNNS142-146PGSG), and antigenic site B (HL156-157KS, KFK158-160GST, NDQI189-192QEQT, A196V). "Native ELISA" analysis and escape mutant selection with two human monoclonal antibodies demonstrated that antibody E05 binds to antigenic site A and 1_C02 binds to site B. We find that most individuals, after vaccination in seasons 2006-07 and/or 2008-09, showed dominance of antigenic site B recognition over antigenic site A. A minority showed dominance of site A in 2006 but these were reduced in 2008 when the vaccine virus had a site A mutation. A better understanding of immunodominance may allow prediction of future antigenic drift and assist in vaccine strain selection.
Date:2012
Reference Type:Literature
PubMed ID:22848649
Journal:PLoS ONE
Journal Volume:7
Article Pages:e41895
Journal ISSN:1932-6203
Article Chemical List:Antibodies, Monoclonal;Antibodies, Neutralizing;Antigens, Viral;Epitopes;Hemagglutinin Glycoproteins, Influenza Virus
Article MeSH List:Antibodies, Monoclonal(immunology); Antibodies, Neutralizing(blood; immunology); Antigens, Viral(genetics; immunology); Epitopes(genetics; immunology); Hemagglutinin Glycoproteins, Influenza Virus(chemistry; genetics; immunology); Humans; Influenza A Virus, H3N2 Subtype(genetics; immunology); Models, Molecular; Mutation; Protein Conformation; Seasons; Species Specificity; Vaccination
Curation Last Updated:2014-07-16 23:13:19