The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain.
Identifieur interne : 000007 ( PubMed/Curation ); précédent : 000006; suivant : 000008The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain.
Auteurs : Hongquan Wan [États-Unis] ; Jin Gao [États-Unis] ; Hua Yang [États-Unis] ; Shuang Yang [États-Unis] ; Ruth Harvey [Royaume-Uni] ; Yao-Qing Chen [États-Unis] ; Nai-Ying Zheng [États-Unis] ; Jessie Chang [États-Unis] ; Paul J. Carney [États-Unis] ; Xing Li [États-Unis] ; Ewan Plant [États-Unis] ; Lianlian Jiang [États-Unis] ; Laura Couzens [États-Unis] ; Carol Wang [États-Unis] ; Shirin Strohmeier [États-Unis] ; Wells W. Wu [États-Unis] ; Rong-Fong Shen [États-Unis] ; Florian Krammer [États-Unis] ; John F. Cipollo [États-Unis] ; Patrick C. Wilson [États-Unis] ; James Stevens [États-Unis] ; Xiu-Feng Wan [États-Unis] ; Maryna C. Eichelberger [États-Unis] ; Zhiping Ye [États-Unis]Source :
- Nature microbiology [ 2058-5276 ] ; 2019.
Abstract
A(H3N2) virus predominated recent influenza seasons, which has resulted in the rigorous investigation of haemagglutinin, but whether neuraminidase (NA) has undergone antigenic change and contributed to the predominance of A(H3N2) virus is unknown. Here, we show that the NA of the circulating A(H3N2) viruses has experienced significant antigenic drift since 2016 compared with the A/Hong Kong/4801/2014 vaccine strain. This antigenic drift was mainly caused by amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468. As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished. This antigenic drift also reduced NA-antibody-based protection against in vivo virus challenge. X-ray crystallography showed that the glycosylation site at residue 245 is within a conserved epitope that overlaps the NA active site, explaining why it impacts antibody binding. Our findings suggest that NA antigenic drift impacts protection against influenza virus infection, thus highlighting the importance of including NA antigenicity for consideration in the optimization of influenza vaccines.
DOI: 10.1038/s41564-019-0522-6
PubMed: 31406333
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Hongquan.wan@fda.hhs.gov.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD</wicri:regionArea></affiliation></author><author><name sortKey="Gao, Jin" sort="Gao, Jin" uniqKey="Gao J" first="Jin" last="Gao">Jin Gao</name><affiliation wicri:level="1"><nlm:affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Hua" sort="Yang, Hua" uniqKey="Yang H" first="Hua" last="Yang">Hua Yang</name><affiliation wicri:level="1"><nlm:affiliation>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Shuang" sort="Yang, Shuang" uniqKey="Yang S" first="Shuang" last="Yang">Shuang Yang</name><affiliation wicri:level="1"><nlm:affiliation>Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD</wicri:regionArea></affiliation></author><author><name sortKey="Harvey, Ruth" sort="Harvey, Ruth" uniqKey="Harvey R" first="Ruth" last="Harvey">Ruth Harvey</name><affiliation wicri:level="1"><nlm:affiliation>National Institute for Biological Standards and Control, Potters Bar, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>National Institute for Biological Standards and Control, Potters Bar</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Yao Qing" sort="Chen, Yao Qing" uniqKey="Chen Y" first="Yao-Qing" last="Chen">Yao-Qing Chen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL</wicri:regionArea></affiliation></author><author><name sortKey="Zheng, Nai Ying" sort="Zheng, Nai Ying" uniqKey="Zheng N" first="Nai-Ying" last="Zheng">Nai-Ying Zheng</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL</wicri:regionArea></affiliation></author><author><name sortKey="Chang, Jessie" sort="Chang, Jessie" uniqKey="Chang J" first="Jessie" last="Chang">Jessie Chang</name><affiliation wicri:level="1"><nlm:affiliation>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA</wicri:regionArea></affiliation></author><author><name sortKey="Carney, Paul J" sort="Carney, Paul J" uniqKey="Carney P" first="Paul J" last="Carney">Paul J. 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Cipollo</name><affiliation wicri:level="1"><nlm:affiliation>Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD</wicri:regionArea></affiliation></author><author><name sortKey="Wilson, Patrick C" sort="Wilson, Patrick C" uniqKey="Wilson P" first="Patrick C" last="Wilson">Patrick C. Wilson</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL</wicri:regionArea></affiliation></author><author><name sortKey="Stevens, James" sort="Stevens, James" uniqKey="Stevens J" first="James" last="Stevens">James Stevens</name><affiliation wicri:level="1"><nlm:affiliation>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA</wicri:regionArea></affiliation></author><author><name sortKey="Wan, Xiu Feng" sort="Wan, Xiu Feng" uniqKey="Wan X" first="Xiu-Feng" last="Wan">Xiu-Feng Wan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS</wicri:regionArea></affiliation></author><author><name sortKey="Eichelberger, Maryna C" sort="Eichelberger, Maryna C" uniqKey="Eichelberger M" first="Maryna C" last="Eichelberger">Maryna C. Eichelberger</name><affiliation wicri:level="1"><nlm:affiliation>Division of Biological Standards and Quantity Control, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Biological Standards and Quantity Control, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD</wicri:regionArea></affiliation></author><author><name sortKey="Ye, Zhiping" sort="Ye, Zhiping" uniqKey="Ye Z" first="Zhiping" last="Ye">Zhiping Ye</name><affiliation wicri:level="1"><nlm:affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:31406333</idno><idno type="pmid">31406333</idno><idno type="doi">10.1038/s41564-019-0522-6</idno><idno type="wicri:Area/PubMed/Corpus">000007</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000007</idno><idno type="wicri:Area/PubMed/Curation">000007</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000007</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain.</title><author><name sortKey="Wan, Hongquan" sort="Wan, Hongquan" uniqKey="Wan H" first="Hongquan" last="Wan">Hongquan Wan</name><affiliation wicri:level="1"><nlm:affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Hongquan.wan@fda.hhs.gov.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD</wicri:regionArea></affiliation></author><author><name sortKey="Gao, Jin" sort="Gao, Jin" uniqKey="Gao J" first="Jin" last="Gao">Jin Gao</name><affiliation wicri:level="1"><nlm:affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Hua" sort="Yang, Hua" uniqKey="Yang H" first="Hua" last="Yang">Hua Yang</name><affiliation wicri:level="1"><nlm:affiliation>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Shuang" sort="Yang, Shuang" uniqKey="Yang S" first="Shuang" last="Yang">Shuang Yang</name><affiliation wicri:level="1"><nlm:affiliation>Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD</wicri:regionArea></affiliation></author><author><name sortKey="Harvey, Ruth" sort="Harvey, Ruth" uniqKey="Harvey R" first="Ruth" last="Harvey">Ruth Harvey</name><affiliation wicri:level="1"><nlm:affiliation>National Institute for Biological Standards and Control, Potters Bar, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>National Institute for Biological Standards and Control, Potters Bar</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Yao Qing" sort="Chen, Yao Qing" uniqKey="Chen Y" first="Yao-Qing" last="Chen">Yao-Qing Chen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL</wicri:regionArea></affiliation></author><author><name sortKey="Zheng, Nai Ying" sort="Zheng, Nai Ying" uniqKey="Zheng N" first="Nai-Ying" last="Zheng">Nai-Ying Zheng</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL</wicri:regionArea></affiliation></author><author><name sortKey="Chang, Jessie" sort="Chang, Jessie" uniqKey="Chang J" first="Jessie" last="Chang">Jessie Chang</name><affiliation wicri:level="1"><nlm:affiliation>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA</wicri:regionArea></affiliation></author><author><name sortKey="Carney, Paul J" sort="Carney, Paul J" uniqKey="Carney P" first="Paul J" last="Carney">Paul J. Carney</name><affiliation wicri:level="1"><nlm:affiliation>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA</wicri:regionArea></affiliation></author><author><name sortKey="Li, Xing" sort="Li, Xing" uniqKey="Li X" first="Xing" last="Li">Xing Li</name><affiliation wicri:level="1"><nlm:affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD</wicri:regionArea></affiliation></author><author><name sortKey="Plant, Ewan" sort="Plant, Ewan" uniqKey="Plant E" first="Ewan" last="Plant">Ewan Plant</name><affiliation wicri:level="1"><nlm:affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD</wicri:regionArea></affiliation></author><author><name sortKey="Jiang, Lianlian" sort="Jiang, Lianlian" uniqKey="Jiang L" first="Lianlian" last="Jiang">Lianlian Jiang</name><affiliation wicri:level="1"><nlm:affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD</wicri:regionArea></affiliation></author><author><name sortKey="Couzens, Laura" sort="Couzens, Laura" uniqKey="Couzens L" first="Laura" last="Couzens">Laura Couzens</name><affiliation wicri:level="1"><nlm:affiliation>Division of Biological Standards and Quantity Control, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Biological Standards and Quantity Control, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Carol" sort="Wang, Carol" uniqKey="Wang C" first="Carol" last="Wang">Carol Wang</name><affiliation wicri:level="1"><nlm:affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD</wicri:regionArea></affiliation></author><author><name sortKey="Strohmeier, Shirin" sort="Strohmeier, Shirin" uniqKey="Strohmeier S" first="Shirin" last="Strohmeier">Shirin Strohmeier</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY</wicri:regionArea></affiliation></author><author><name sortKey="Wu, Wells W" sort="Wu, Wells W" uniqKey="Wu W" first="Wells W" last="Wu">Wells W. Wu</name><affiliation wicri:level="1"><nlm:affiliation>Facility for Biotechnology Resources, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Facility for Biotechnology Resources, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD</wicri:regionArea></affiliation></author><author><name sortKey="Shen, Rong Fong" sort="Shen, Rong Fong" uniqKey="Shen R" first="Rong-Fong" last="Shen">Rong-Fong Shen</name><affiliation wicri:level="1"><nlm:affiliation>Facility for Biotechnology Resources, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Facility for Biotechnology Resources, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD</wicri:regionArea></affiliation></author><author><name sortKey="Krammer, Florian" sort="Krammer, Florian" uniqKey="Krammer F" first="Florian" last="Krammer">Florian Krammer</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY</wicri:regionArea></affiliation></author><author><name sortKey="Cipollo, John F" sort="Cipollo, John F" uniqKey="Cipollo J" first="John F" last="Cipollo">John F. Cipollo</name><affiliation wicri:level="1"><nlm:affiliation>Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD</wicri:regionArea></affiliation></author><author><name sortKey="Wilson, Patrick C" sort="Wilson, Patrick C" uniqKey="Wilson P" first="Patrick C" last="Wilson">Patrick C. Wilson</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL</wicri:regionArea></affiliation></author><author><name sortKey="Stevens, James" sort="Stevens, James" uniqKey="Stevens J" first="James" last="Stevens">James Stevens</name><affiliation wicri:level="1"><nlm:affiliation>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA</wicri:regionArea></affiliation></author><author><name sortKey="Wan, Xiu Feng" sort="Wan, Xiu Feng" uniqKey="Wan X" first="Xiu-Feng" last="Wan">Xiu-Feng Wan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS</wicri:regionArea></affiliation></author><author><name sortKey="Eichelberger, Maryna C" sort="Eichelberger, Maryna C" uniqKey="Eichelberger M" first="Maryna C" last="Eichelberger">Maryna C. Eichelberger</name><affiliation wicri:level="1"><nlm:affiliation>Division of Biological Standards and Quantity Control, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Biological Standards and Quantity Control, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD</wicri:regionArea></affiliation></author><author><name sortKey="Ye, Zhiping" sort="Ye, Zhiping" uniqKey="Ye Z" first="Zhiping" last="Ye">Zhiping Ye</name><affiliation wicri:level="1"><nlm:affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD</wicri:regionArea></affiliation></author></analytic><series><title level="j">Nature microbiology</title><idno type="eISSN">2058-5276</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A(H3N2) virus predominated recent influenza seasons, which has resulted in the rigorous investigation of haemagglutinin, but whether neuraminidase (NA) has undergone antigenic change and contributed to the predominance of A(H3N2) virus is unknown. Here, we show that the NA of the circulating A(H3N2) viruses has experienced significant antigenic drift since 2016 compared with the A/Hong Kong/4801/2014 vaccine strain. This antigenic drift was mainly caused by amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468. As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished. This antigenic drift also reduced NA-antibody-based protection against in vivo virus challenge. X-ray crystallography showed that the glycosylation site at residue 245 is within a conserved epitope that overlaps the NA active site, explaining why it impacts antibody binding. Our findings suggest that NA antigenic drift impacts protection against influenza virus infection, thus highlighting the importance of including NA antigenicity for consideration in the optimization of influenza vaccines.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">31406333</PMID><DateRevised><Year>2020</Year><Month>03</Month><Day>11</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">2058-5276</ISSN><JournalIssue CitedMedium="Internet"><Volume>4</Volume><Issue>12</Issue><PubDate><Year>2019</Year><Month>12</Month></PubDate></JournalIssue><Title>Nature microbiology</Title><ISOAbbreviation>Nat Microbiol</ISOAbbreviation></Journal><ArticleTitle>The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain.</ArticleTitle><Pagination><MedlinePgn>2216-2225</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41564-019-0522-6</ELocationID><Abstract><AbstractText>A(H3N2) virus predominated recent influenza seasons, which has resulted in the rigorous investigation of haemagglutinin, but whether neuraminidase (NA) has undergone antigenic change and contributed to the predominance of A(H3N2) virus is unknown. Here, we show that the NA of the circulating A(H3N2) viruses has experienced significant antigenic drift since 2016 compared with the A/Hong Kong/4801/2014 vaccine strain. This antigenic drift was mainly caused by amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468. As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished. This antigenic drift also reduced NA-antibody-based protection against in vivo virus challenge. X-ray crystallography showed that the glycosylation site at residue 245 is within a conserved epitope that overlaps the NA active site, explaining why it impacts antibody binding. Our findings suggest that NA antigenic drift impacts protection against influenza virus infection, thus highlighting the importance of including NA antigenicity for consideration in the optimization of influenza vaccines.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wan</LastName><ForeName>Hongquan</ForeName><Initials>H</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-6374-0343</Identifier><AffiliationInfo><Affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Hongquan.wan@fda.hhs.gov.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gao</LastName><ForeName>Jin</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Hua</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Shuang</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Harvey</LastName><ForeName>Ruth</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>National Institute for Biological Standards and Control, Potters Bar, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Yao-Qing</ForeName><Initials>YQ</Initials><AffiliationInfo><Affiliation>Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zheng</LastName><ForeName>Nai-Ying</ForeName><Initials>NY</Initials><AffiliationInfo><Affiliation>Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chang</LastName><ForeName>Jessie</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Carney</LastName><ForeName>Paul J</ForeName><Initials>PJ</Initials><AffiliationInfo><Affiliation>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Xing</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Plant</LastName><ForeName>Ewan</ForeName><Initials>E</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-0166-5939</Identifier><AffiliationInfo><Affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jiang</LastName><ForeName>Lianlian</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Couzens</LastName><ForeName>Laura</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Division of Biological Standards and Quantity Control, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Carol</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Strohmeier</LastName><ForeName>Shirin</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Wells W</ForeName><Initials>WW</Initials><AffiliationInfo><Affiliation>Facility for Biotechnology Resources, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shen</LastName><ForeName>Rong-Fong</ForeName><Initials>RF</Initials><AffiliationInfo><Affiliation>Facility for Biotechnology Resources, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Krammer</LastName><ForeName>Florian</ForeName><Initials>F</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-4121-776X</Identifier><AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cipollo</LastName><ForeName>John F</ForeName><Initials>JF</Initials><AffiliationInfo><Affiliation>Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wilson</LastName><ForeName>Patrick C</ForeName><Initials>PC</Initials><AffiliationInfo><Affiliation>Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stevens</LastName><ForeName>James</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wan</LastName><ForeName>Xiu-Feng</ForeName><Initials>XF</Initials><AffiliationInfo><Affiliation>Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Eichelberger</LastName><ForeName>Maryna C</ForeName><Initials>MC</Initials><AffiliationInfo><Affiliation>Division of Biological Standards and Quantity Control, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ye</LastName><ForeName>Zhiping</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AI116744</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P20 GM103476</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI147640</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P20 GM103646</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R15 AI107702</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>RC1 AI086830</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>08</Month><Day>12</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Nat Microbiol</MedlineTA><NlmUniqueID>101674869</NlmUniqueID><ISSNLinking>2058-5276</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>12</Month><Day>20</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>06</Month><Day>24</Day></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2019</Year><Month>12</Month><Day>01</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>8</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Curation/RBID.i -Sk "pubmed:31406333" \
| HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Curation/biblio.hfd \
| NlmPubMed2Wicri -a H2N2V1
| This area was generated with Dilib version V0.6.33. |  |