{"corpus_id":12545316,"paper_sha":"720853c9540250456c32766e12cc9d5b10df13df","doi":"10.1371/journal.pone.0041895","arxiv_id":null,"pmid":22848649,"pmcid":"3405050","mag_id":2011840149,"dblp_id":null,"acl_id":null,"title":"Immunodominance of Antigenic Site B over Site A of Hemagglutinin of Recent H3N2 Influenza Viruses","year":2012,"publication_date":"2012-07-25","venue":"PLoS ONE","journal":{"name":"PLoS ONE","pages":null,"volume":"7"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, N.I.H., Extramural"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":53,"citation_count":110,"influential_citation_count":6,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Antibodies, Monoclonal","mj":false,"qs":[{"q":"immunology","mj":false,"ui":"Q000276"}],"ui":"D000911"},{"d":"Antibodies, Neutralizing","mj":false,"qs":[{"q":"blood","mj":false,"ui":"Q000097"},{"q":"immunology","mj":false,"ui":"Q000276"}],"ui":"D057134"},{"d":"Antigens, Viral","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"immunology","mj":true,"ui":"Q000276"}],"ui":"D000956"},{"d":"Epitopes","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"immunology","mj":true,"ui":"Q000276"}],"ui":"D000939"},{"d":"Hemagglutinin Glycoproteins, Influenza Virus","mj":false,"qs":[{"q":"chemistry","mj":false,"ui":"Q000737"},{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"immunology","mj":true,"ui":"Q000276"}],"ui":"D019267"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Influenza A Virus, H3N2 Subtype","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"immunology","mj":true,"ui":"Q000276"}],"ui":"D053122"},{"d":"Models, Molecular","mj":false,"ui":"D008958"},{"d":"Mutation","mj":false,"ui":"D009154"},{"d":"Protein Conformation","mj":false,"ui":"D011487"},{"d":"Seasons","mj":false,"ui":"D012621"},{"d":"Species Specificity","mj":false,"ui":"D013045"},{"d":"Vaccination","mj":false,"ui":"D014611"}],"chemicals":[{"n":"Antibodies, Monoclonal","ui":"D000911","reg":"0"},{"n":"Antibodies, Neutralizing","ui":"D057134","reg":"0"},{"n":"Antigens, Viral","ui":"D000956","reg":"0"},{"n":"Epitopes","ui":"D000939","reg":"0"},{"n":"Hemagglutinin Glycoproteins, Influenza Virus","ui":"D019267","reg":"0"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0041895&type=printable","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/720853c9540250456c32766e12cc9d5b10df13df","s2_open_access_license":"CCBY","s2_open_access_status":"GOLD","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"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.","claims":[{"public_id":"cl_5a18db4ee342acaba472bc3b8d476093","status":"active","text":"A minority showed dominance of site A in 2006, but this group was smaller in 2008 after the vaccine virus acquired a site A mutation.","confidence":0.91,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_5a18db4ee342acaba472bc3b8d476093"},{"public_id":"cl_86157af8478545a61c5d007632fc785c","status":"active","text":"Antibody E05 binds to antigenic site A and 1_C02 binds to site B.","confidence":0.99,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_86157af8478545a61c5d007632fc785c"},{"public_id":"cl_acdb516616cfd8d98daae11304b6d916","status":"active","text":"Most vaccinated individuals showed dominance of antigenic site B recognition over antigenic site A.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_acdb516616cfd8d98daae11304b6d916"}],"concepts":[{"public_id":"co_1954e9c915a58ae7112ae0c6a5e514d3","status":"active","name":"immunodominance","description":"The relative dominance of immune recognition toward one antigenic site over another.","types":["immunological phenomenon"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_1954e9c915a58ae7112ae0c6a5e514d3"},{"public_id":"co_2c56c2eb162b00770bffa61dea237e79","status":"active","name":"2008–09 formulation","description":"The 2008–09 seasonal influenza vaccine formulation containing the H3 component A/Uruguay/716/07.","types":["vaccine formulation"],"aliases":["2008-09 formulation"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_2c56c2eb162b00770bffa61dea237e79"},{"public_id":"co_3dd08b4006c317163080e5e199f0145f","status":"active","name":"hemagglutinin","description":"The influenza surface glycoprotein targeted by antibodies and used here for antigenic-site analysis.","types":["viral protein"],"aliases":["HA"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_3dd08b4006c317163080e5e199f0145f"},{"public_id":"co_45763be663c9ebec0247b43ef02cddbc","status":"active","name":"antigenic site B","description":"One of the mapped antigenic regions on H3 hemagglutinin used to assess antibody recognition.","types":["epitope"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_45763be663c9ebec0247b43ef02cddbc"},{"public_id":"co_4a1b37c86133fe9deaa5fcef68d994a4","status":"active","name":"antibody E05","description":"A human monoclonal antibody used to map binding to antigenic site A.","types":["antibody"],"aliases":["E05"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_4a1b37c86133fe9deaa5fcef68d994a4"},{"public_id":"co_57a64fa26ca187c9d0cfb1ec08ad4fb9","status":"active","name":"1_C02","description":"A human monoclonal antibody used to map binding to antigenic site B.","types":["antibody"],"aliases":["1C02"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_57a64fa26ca187c9d0cfb1ec08ad4fb9"},{"public_id":"co_65cdcebe6c859152fd785cddd7cbbb99","status":"active","name":"H3N2 influenza viruses","description":"Human influenza A viruses of the H3N2 subtype that circulate and accumulate antigenic changes.","types":["virus"],"aliases":["H3N2"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_65cdcebe6c859152fd785cddd7cbbb99"},{"public_id":"co_a1b36a50776fa9160d87062a6bcccc45","status":"active","name":"2006–07 trivalent subunit influenza vaccine","description":"The 2006–07 seasonal influenza vaccine containing the H3 component A/Wisconsin/67/05.","types":["vaccine"],"aliases":["2006-07 trivalent subunit influenza vaccine"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_a1b36a50776fa9160d87062a6bcccc45"},{"public_id":"co_a5fd4691d23c00eb3eb27a70f083010f","status":"active","name":"site A mutation","description":"A mutation in antigenic site A of the vaccine virus that altered the site relative to earlier strains.","types":["mutation"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_a5fd4691d23c00eb3eb27a70f083010f"},{"public_id":"co_d5673e46d569f99405ef74299e949c7d","status":"active","name":"antigenic site A","description":"One of the mapped antigenic regions on H3 hemagglutinin used to assess antibody recognition.","types":["epitope"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_d5673e46d569f99405ef74299e949c7d"}],"external_ids":{"DOI":"10.1371/journal.pone.0041895","ArXiv":null,"PubMed":22848649,"PubMedCentral":"3405050","MAG":2011840149,"DBLP":null,"ACL":null},"open_access":{"is_open_access":true,"pdf_url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0041895&type=printable","landing_url":"https://www.semanticscholar.org/paper/720853c9540250456c32766e12cc9d5b10df13df","source":"semantic_scholar","pdf_url_source":"semantic_scholar_open_access_pdf","license":"CCBY","status":"GOLD","reason":null},"reference_availability":{"status":"available","references_indexed":true,"full_text_available":false,"full_text_source":null,"count_basis":"semantic_scholar_metadata","extraction_status":"not_applicable","reason":null},"source":{"provider":"episteme2","base_corpus":"semantic_scholar_dump","freshness_mode":"unknown","basis":["semantic_scholar_metadata","postgres_metadata"],"limits":["paper metadata is based on indexed upstream scholarly datasets","claims and concepts are available only for extracted papers","absence of claims or concepts means no extracted graph data is available in this response"],"status":"available","degraded":false,"degraded_reasons":[],"diagnostics":{"status":"available","degraded":false,"degraded_reasons":[],"metadata_status":"available","graph_status":"available","abstract_status":"available"},"source_flags":5},"paper_id":632011,"paper_uid":"82e69f2f-4550-41e2-86f6-b92561f39cf2","canonical_identity":{"paper_id":632011,"paper_uid":"82e69f2f-4550-41e2-86f6-b92561f39cf2","identity_status":"available","lookup_basis":"semantic_scholar_external_id","compatibility_path":"corpus_id"},"url":"https://sah.borca.ai/papers/12545316"}