Serveur d'exploration H2N2

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The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain

Identifieur interne : 000838 ( Pmc/Corpus ); précédent : 000837; suivant : 000839

The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain

Auteurs : Hongquan Wan ; Jin Gao ; Hua Yang ; Shuang Yang ; Ruth Harvey ; Yao-Qing Chen ; Nai-Ying Zheng ; Jessie Chang ; Paul J. Carney ; Xing Li ; Ewan Plant ; Lianlian Jiang ; Laura Couzens ; Carol Wang ; Shirin Strohmeier ; Wells W. Wu ; Rong-Fong Shen ; Florian Krammer ; John F. Cipollo ; Patrick C. Wilson ; James Stevens ; Xiu-Feng Wan ; Maryna C. Eichelberger ; Zhiping Ye

Source :

RBID : PMC:6879794

Abstract

The predominance of A(H3N2) virus in recent influenza seasons has resulted in rigorous investigation on hemagglutinin, but little attention has been paid to the potential role of neuraminidase (NA). Here we show that since 2016, the S245N/S247T (introducing an N-linked glycosylation site at residue 245) and P468H mutations contributed to antigenic drift of the NA of circulating A(H3N2) viruses, compared with earlier viruses represented by the A/Hong Kong/4801/2014 vaccine strain. As a result, some human monoclonal antibodies, including those that have broad-reactivity with NA of the reference 1957 A(H2N2) and 1968 A(H3N2) pandemic viruses as well as contemporary seasonal A(H3N2) strains, lost binding to NA. This antigenic drift also reduced NA antibody-based protection against in vivo virus challenge. X-ray crystallography showed that the NA245 glycosylation site is within a conserved epitope that overlaps the NA active site, explaining why it impacts antibody binding. Our findings suggest that NA antigenic drift may impact protection against influenza virus infection, highlighting the importance of including NA antigenicity for consideration in optimizing influenza vaccines.


Url:
DOI: 10.1038/s41564-019-0522-6
PubMed: 31406333
PubMed Central: 6879794

Links to Exploration step

PMC:6879794

Le document en format XML

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<name sortKey="Couzens, Laura" sort="Couzens, Laura" uniqKey="Couzens L" first="Laura" last="Couzens">Laura Couzens</name>
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<name sortKey="Wang, Carol" sort="Wang, Carol" uniqKey="Wang C" first="Carol" last="Wang">Carol Wang</name>
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<name sortKey="Strohmeier, Shirin" sort="Strohmeier, Shirin" uniqKey="Strohmeier S" first="Shirin" last="Strohmeier">Shirin Strohmeier</name>
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<nlm:aff id="A7">Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA</nlm:aff>
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<name sortKey="Wu, Wells W" sort="Wu, Wells W" uniqKey="Wu W" first="Wells W." last="Wu">Wells W. Wu</name>
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<name sortKey="Shen, Rong Fong" sort="Shen, Rong Fong" uniqKey="Shen R" first="Rong-Fong" last="Shen">Rong-Fong Shen</name>
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<name sortKey="Krammer, Florian" sort="Krammer, Florian" uniqKey="Krammer F" first="Florian" last="Krammer">Florian Krammer</name>
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<nlm:aff id="A6">Division of Biological Standards and Quantity Control, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA</nlm:aff>
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<title xml:lang="en" level="a" type="main">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>
<nlm:aff id="A1">Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA</nlm:aff>
</affiliation>
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<name sortKey="Gao, Jin" sort="Gao, Jin" uniqKey="Gao J" first="Jin" last="Gao">Jin Gao</name>
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<nlm:aff id="A1">Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA</nlm:aff>
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<author>
<name sortKey="Yang, Hua" sort="Yang, Hua" uniqKey="Yang H" first="Hua" last="Yang">Hua Yang</name>
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<nlm:aff id="A2">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30033, USA</nlm:aff>
</affiliation>
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<author>
<name sortKey="Yang, Shuang" sort="Yang, Shuang" uniqKey="Yang S" first="Shuang" last="Yang">Shuang Yang</name>
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<nlm:aff id="A3">Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA</nlm:aff>
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<name sortKey="Harvey, Ruth" sort="Harvey, Ruth" uniqKey="Harvey R" first="Ruth" last="Harvey">Ruth Harvey</name>
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<nlm:aff id="A4">National Institute of Biological Standards and Control, Potters Bar, EN6 3QG, UK</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Chen, Yao Qing" sort="Chen, Yao Qing" uniqKey="Chen Y" first="Yao-Qing" last="Chen">Yao-Qing Chen</name>
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<nlm:aff id="A5">Department of Medicine, Section of Rheumatology, the Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA</nlm:aff>
</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>
<nlm:aff id="A5">Department of Medicine, Section of Rheumatology, the Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Chang, Jessie" sort="Chang, Jessie" uniqKey="Chang J" first="Jessie" last="Chang">Jessie Chang</name>
<affiliation>
<nlm:aff id="A2">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30033, USA</nlm:aff>
</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>
<nlm:aff id="A2">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30033, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Li, Xing" sort="Li, Xing" uniqKey="Li X" first="Xing" last="Li">Xing Li</name>
<affiliation>
<nlm:aff id="A1">Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Plant, Ewan" sort="Plant, Ewan" uniqKey="Plant E" first="Ewan" last="Plant">Ewan Plant</name>
<affiliation>
<nlm:aff id="A1">Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Jiang, Lianlian" sort="Jiang, Lianlian" uniqKey="Jiang L" first="Lianlian" last="Jiang">Lianlian Jiang</name>
<affiliation>
<nlm:aff id="A1">Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Couzens, Laura" sort="Couzens, Laura" uniqKey="Couzens L" first="Laura" last="Couzens">Laura Couzens</name>
<affiliation>
<nlm:aff id="A6">Division of Biological Standards and Quantity Control, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Wang, Carol" sort="Wang, Carol" uniqKey="Wang C" first="Carol" last="Wang">Carol Wang</name>
<affiliation>
<nlm:aff id="A1">Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Strohmeier, Shirin" sort="Strohmeier, Shirin" uniqKey="Strohmeier S" first="Shirin" last="Strohmeier">Shirin Strohmeier</name>
<affiliation>
<nlm:aff id="A7">Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA</nlm:aff>
</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>
<nlm:aff id="A8">Facility for Biotechnology Resources, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA</nlm:aff>
</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>
<nlm:aff id="A8">Facility for Biotechnology Resources, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Krammer, Florian" sort="Krammer, Florian" uniqKey="Krammer F" first="Florian" last="Krammer">Florian Krammer</name>
<affiliation>
<nlm:aff id="A7">Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA</nlm:aff>
</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>
<nlm:aff id="A3">Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA</nlm:aff>
</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>
<nlm:aff id="A5">Department of Medicine, Section of Rheumatology, the Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Stevens, James" sort="Stevens, James" uniqKey="Stevens J" first="James" last="Stevens">James Stevens</name>
<affiliation>
<nlm:aff id="A2">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30033, USA</nlm:aff>
</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>
<nlm:aff id="A9">Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS 39762, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Eichelberger, Maryna C" sort="Eichelberger, Maryna C" uniqKey="Eichelberger M" first="Maryna C." last="Eichelberger">Maryna C. Eichelberger</name>
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<nlm:aff id="A6">Division of Biological Standards and Quantity Control, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Ye, Zhiping" sort="Ye, Zhiping" uniqKey="Ye Z" first="Zhiping" last="Ye">Zhiping Ye</name>
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<nlm:aff id="A1">Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA</nlm:aff>
</affiliation>
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<p id="P3">The predominance of A(H3N2) virus in recent influenza seasons has resulted in rigorous investigation on hemagglutinin, but little attention has been paid to the potential role of neuraminidase (NA). Here we show that since 2016, the S245N/S247T (introducing an
<italic>N</italic>
-linked glycosylation site at residue 245) and P468H mutations contributed to antigenic drift of the NA of circulating A(H3N2) viruses, compared with earlier viruses represented by the A/Hong Kong/4801/2014 vaccine strain. As a result, some human monoclonal antibodies, including those that have broad-reactivity with NA of the reference 1957 A(H2N2) and 1968 A(H3N2) pandemic viruses as well as contemporary seasonal A(H3N2) strains, lost binding to NA. This antigenic drift also reduced NA antibody-based protection against
<italic>in vivo</italic>
virus challenge. X-ray crystallography showed that the NA245 glycosylation site is within a conserved epitope that overlaps the NA active site, explaining why it impacts antibody binding. Our findings suggest that NA antigenic drift may impact protection against influenza virus infection, highlighting the importance of including NA antigenicity for consideration in optimizing influenza vaccines.</p>
</div>
</front>
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<contrib contrib-type="author">
<name>
<surname>Wan</surname>
<given-names>Hongquan</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref rid="CR1" ref-type="corresp">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gao</surname>
<given-names>Jin</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yang</surname>
<given-names>Hua</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yang</surname>
<given-names>Shuang</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Harvey</surname>
<given-names>Ruth</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chen</surname>
<given-names>Yao-Qing</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zheng</surname>
<given-names>Nai-Ying</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chang</surname>
<given-names>Jessie</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Carney</surname>
<given-names>Paul J.</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Li</surname>
<given-names>Xing</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Plant</surname>
<given-names>Ewan</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Jiang</surname>
<given-names>Lianlian</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Couzens</surname>
<given-names>Laura</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wang</surname>
<given-names>Carol</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Strohmeier</surname>
<given-names>Shirin</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wu</surname>
<given-names>Wells W.</given-names>
</name>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Shen</surname>
<given-names>Rong-Fong</given-names>
</name>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Krammer</surname>
<given-names>Florian</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cipollo</surname>
<given-names>John F.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wilson</surname>
<given-names>Patrick C.</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Stevens</surname>
<given-names>James</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wan</surname>
<given-names>Xiu-Feng</given-names>
</name>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Eichelberger</surname>
<given-names>Maryna C.</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ye</surname>
<given-names>Zhiping</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
</contrib-group>
<aff id="A1">
<label>1</label>
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA</aff>
<aff id="A2">
<label>2</label>
Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30033, USA</aff>
<aff id="A3">
<label>3</label>
Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA</aff>
<aff id="A4">
<label>4</label>
National Institute of Biological Standards and Control, Potters Bar, EN6 3QG, UK</aff>
<aff id="A5">
<label>5</label>
Department of Medicine, Section of Rheumatology, the Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA</aff>
<aff id="A6">
<label>6</label>
Division of Biological Standards and Quantity Control, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA</aff>
<aff id="A7">
<label>7</label>
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA</aff>
<aff id="A8">
<label>8</label>
Facility for Biotechnology Resources, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA</aff>
<aff id="A9">
<label>9</label>
Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS 39762, USA</aff>
<author-notes>
<fn fn-type="con" id="FN1">
<p id="P1">Author contributions</p>
<p id="P2">H.Q.W. conceived the project, designed and supervised the work, analyzed data and wrote the manuscript. J.G. rescued reassortant viruses, performed serological assays and assisted with animal studies. H.Y., J.C., and P.J.C. expressed NA and defined the crystal structure. S.Y. W.W.W, R.F.S., and J.F.C. analyzed the glycans with mass-spectrometry. R.H. contributed to serological assays. Y.Q.C., N.Y.Z. and P.C.W. prepared human monoclonal antibodies (mAbs). X.L. and E.P. performed Western blot and virus counting. L.C., L.L.J, and C.W. characterized mouse mAbs. S.S. and F.K. helped with animal experiments. J.S. supervised the crystal structural work. X.F.W. analyzed NA sequences and generated antigenic maps. M.C.E. and Z.P.Y. provided suggestions for the work. All authors helped improve the manuscript.</p>
</fn>
<corresp id="CR1">
<label>*</label>
<bold>Correspondence and requests for materials</bold>
should be addressed to Hongquan Wan,
<email>Hongquan.wan@fda.hhs.gov</email>
</corresp>
<fn fn-type="COI-statement" id="FN2">
<p id="P45">Competing interests</p>
<p id="P46">The authors declare no competing interests.</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted">
<day>15</day>
<month>8</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="epub">
<day>12</day>
<month>8</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="ppub">
<month>12</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>01</day>
<month>12</month>
<year>2019</year>
</pub-date>
<volume>4</volume>
<issue>12</issue>
<fpage>2216</fpage>
<lpage>2225</lpage>
<pmc-comment>elocation-id from pubmed: 10.1038/s41564-019-0522-6</pmc-comment>
<abstract id="ABS1">
<p id="P3">The predominance of A(H3N2) virus in recent influenza seasons has resulted in rigorous investigation on hemagglutinin, but little attention has been paid to the potential role of neuraminidase (NA). Here we show that since 2016, the S245N/S247T (introducing an
<italic>N</italic>
-linked glycosylation site at residue 245) and P468H mutations contributed to antigenic drift of the NA of circulating A(H3N2) viruses, compared with earlier viruses represented by the A/Hong Kong/4801/2014 vaccine strain. As a result, some human monoclonal antibodies, including those that have broad-reactivity with NA of the reference 1957 A(H2N2) and 1968 A(H3N2) pandemic viruses as well as contemporary seasonal A(H3N2) strains, lost binding to NA. This antigenic drift also reduced NA antibody-based protection against
<italic>in vivo</italic>
virus challenge. X-ray crystallography showed that the NA245 glycosylation site is within a conserved epitope that overlaps the NA active site, explaining why it impacts antibody binding. Our findings suggest that NA antigenic drift may impact protection against influenza virus infection, highlighting the importance of including NA antigenicity for consideration in optimizing influenza vaccines.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>

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