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Influenza infection in humans induces broadly cross-reactive and protective neuraminidase-reactive antibodies

Identifieur interne : 000804 ( Pmc/Curation ); précédent : 000803; suivant : 000805

Influenza infection in humans induces broadly cross-reactive and protective neuraminidase-reactive antibodies

Auteurs : Yaoqing Chen [États-Unis] ; Teddy John Wohlbold [États-Unis] ; Nai-Ying Zheng [États-Unis] ; Min Huang [États-Unis] ; Yunping Huang [États-Unis] ; Karlynn E. Neu [États-Unis] ; Jiwon Lee [États-Unis] ; Hongquan Wan [États-Unis] ; Karla Thatcher Rojas [États-Unis] ; Ericka Kirkpatrick [États-Unis] ; Carole Henry [États-Unis] ; Anna-Karin E. Palm [États-Unis] ; Christopher T. Stamper [États-Unis] ; Linda Yu-Ling Lan [États-Unis] ; David J. Topham [États-Unis] ; John Treanor [États-Unis] ; Jens Wrammert [États-Unis] ; Rafi Ahmed [États-Unis] ; Maryna C. Eichelberger [États-Unis] ; George Georgiou [États-Unis] ; Florian Krammer [États-Unis] ; Patrick C. Wilson [États-Unis]

Source :

RBID : PMC:5890936

Abstract

SUMMARY

Antibodies to the hemagglutinin (HA) and neuraminidase (NA) glycoproteins are the major mediators of protection against influenza virus infection. Here, we report that current influenza vaccines poorly display key NA epitopes and rarely induce NA-reactive B cells. Conversely, influenza virus infection induces NA-reactive B cells at a frequency that approaches (H1N1) or exceeds (H3N2) that of HA-reactive B cells. NA-reactive antibodies display broad binding activity spanning the entire history of influenza A virus circulation in humans, including the original pandemic strains of both H1N1 and H3N2 subtypes. The antibodies robustly inhibit the enzymatic activity of NA, including oseltamivir-resistant variants, and provide robust prophylactic protection in vivo, including against avian H5N1 viruses. When used therapeutically, NA-reactive antibodies protected mice from lethal influenza virus challenge even 48-hours post-infection. These findings strongly suggest that influenza vaccines should be optimized to improve targeting of NA for durable and broad protection against divergent influenza strains.


Url:
DOI: 10.1016/j.cell.2018.03.030
PubMed: 29625056
PubMed Central: 5890936

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PMC:5890936

Le document en format XML

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<name sortKey="Ahmed, Rafi" sort="Ahmed, Rafi" uniqKey="Ahmed R" first="Rafi" last="Ahmed">Rafi Ahmed</name>
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<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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<title xml:lang="en" level="a" type="main">Influenza infection in humans induces broadly cross-reactive and protective neuraminidase-reactive antibodies</title>
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<name sortKey="Chen, Yaoqing" sort="Chen, Yaoqing" uniqKey="Chen Y" first="Yaoqing" last="Chen">Yaoqing Chen</name>
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<nlm:aff id="A1">Department of Medicine, Section of Rheumatology, the Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA</nlm:aff>
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<wicri:regionArea>Department of Medicine, Section of Rheumatology, the Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637</wicri:regionArea>
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<name sortKey="Wohlbold, Teddy John" sort="Wohlbold, Teddy John" uniqKey="Wohlbold T" first="Teddy John" last="Wohlbold">Teddy John Wohlbold</name>
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<nlm:aff id="A2">Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA</nlm:aff>
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<wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029</wicri:regionArea>
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<name sortKey="Zheng, Nai Ying" sort="Zheng, Nai Ying" uniqKey="Zheng N" first="Nai-Ying" last="Zheng">Nai-Ying Zheng</name>
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<nlm:aff id="A1">Department of Medicine, Section of Rheumatology, the Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA</nlm:aff>
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<name sortKey="Lee, Jiwon" sort="Lee, Jiwon" uniqKey="Lee J" first="Jiwon" last="Lee">Jiwon Lee</name>
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<name sortKey="Wan, Hongquan" sort="Wan, Hongquan" uniqKey="Wan H" first="Hongquan" last="Wan">Hongquan Wan</name>
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<name sortKey="Rojas, Karla Thatcher" sort="Rojas, Karla Thatcher" uniqKey="Rojas K" first="Karla Thatcher" last="Rojas">Karla Thatcher Rojas</name>
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<wicri:regionArea>Department of Medicine, Section of Rheumatology, the Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637</wicri:regionArea>
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<name sortKey="Kirkpatrick, Ericka" sort="Kirkpatrick, Ericka" uniqKey="Kirkpatrick E" first="Ericka" last="Kirkpatrick">Ericka Kirkpatrick</name>
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<wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029</wicri:regionArea>
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<name sortKey="Henry, Carole" sort="Henry, Carole" uniqKey="Henry C" first="Carole" last="Henry">Carole Henry</name>
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<wicri:regionArea>Department of Medicine, Section of Rheumatology, the Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637</wicri:regionArea>
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<name sortKey="Palm, Anna Karin E" sort="Palm, Anna Karin E" uniqKey="Palm A" first="Anna-Karin E." last="Palm">Anna-Karin E. Palm</name>
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<nlm:aff id="A1">Department of Medicine, Section of Rheumatology, the Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, Section of Rheumatology, the Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Stamper, Christopher T" sort="Stamper, Christopher T" uniqKey="Stamper C" first="Christopher T." last="Stamper">Christopher T. Stamper</name>
<affiliation wicri:level="1">
<nlm:aff id="A3">The Committee on Immunology, University of Chicago, Chicago, IL 60637, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Committee on Immunology, University of Chicago, Chicago, IL 60637</wicri:regionArea>
</affiliation>
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<author>
<name sortKey="Lan, Linda Yu Ling" sort="Lan, Linda Yu Ling" uniqKey="Lan L" first="Linda Yu-Ling" last="Lan">Linda Yu-Ling Lan</name>
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<nlm:aff id="A3">The Committee on Immunology, University of Chicago, Chicago, IL 60637, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Committee on Immunology, University of Chicago, Chicago, IL 60637</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Topham, David J" sort="Topham, David J" uniqKey="Topham D" first="David J." last="Topham">David J. Topham</name>
<affiliation wicri:level="1">
<nlm:aff id="A6">Center for Vaccine Biology & Immunology, Department of Microbiology & Immunology, University of Rochester Medical center, Rochester, NY 14642, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Vaccine Biology & Immunology, Department of Microbiology & Immunology, University of Rochester Medical center, Rochester, NY 14642</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Treanor, John" sort="Treanor, John" uniqKey="Treanor J" first="John" last="Treanor">John Treanor</name>
<affiliation wicri:level="1">
<nlm:aff id="A7">Division of Infectious Disease, Department of Medicine, University of Rochester Medical center, Rochester, NY 14642, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Infectious Disease, Department of Medicine, University of Rochester Medical center, Rochester, NY 14642</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Wrammert, Jens" sort="Wrammert, Jens" uniqKey="Wrammert J" first="Jens" last="Wrammert">Jens Wrammert</name>
<affiliation wicri:level="1">
<nlm:aff id="A8">Emory Vaccine Center, Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Emory Vaccine Center, Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Ahmed, Rafi" sort="Ahmed, Rafi" uniqKey="Ahmed R" first="Rafi" last="Ahmed">Rafi Ahmed</name>
<affiliation wicri:level="1">
<nlm:aff id="A8">Emory Vaccine Center, Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Emory Vaccine Center, Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322</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:aff id="A5">Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA</nlm:aff>
<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 20993</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Georgiou, George" sort="Georgiou, George" uniqKey="Georgiou G" first="George" last="Georgiou">George Georgiou</name>
<affiliation wicri:level="1">
<nlm:aff id="A4">Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78731, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78731</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:aff id="A2">Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029</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:aff id="A1">Department of Medicine, Section of Rheumatology, the Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, Section of Rheumatology, the Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Cell</title>
<idno type="ISSN">0092-8674</idno>
<idno type="eISSN">1097-4172</idno>
<imprint>
<date when="2018">2018</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<title>SUMMARY</title>
<p id="P1">Antibodies to the hemagglutinin (HA) and neuraminidase (NA) glycoproteins are the major mediators of protection against influenza virus infection. Here, we report that current influenza vaccines poorly display key NA epitopes and rarely induce NA-reactive B cells. Conversely, influenza virus infection induces NA-reactive B cells at a frequency that approaches (H1N1) or exceeds (H3N2) that of HA-reactive B cells. NA-reactive antibodies display broad binding activity spanning the entire history of influenza A virus circulation in humans, including the original pandemic strains of both H1N1 and H3N2 subtypes. The antibodies robustly inhibit the enzymatic activity of NA, including oseltamivir-resistant variants, and provide robust prophylactic protection
<italic>in vivo</italic>
, including against avian H5N1 viruses. When used therapeutically, NA-reactive antibodies protected mice from lethal influenza virus challenge even 48-hours post-infection. These findings strongly suggest that influenza vaccines should be optimized to improve targeting of NA for durable and broad protection against divergent influenza strains.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-journal-id">0413066</journal-id>
<journal-id journal-id-type="pubmed-jr-id">2830</journal-id>
<journal-id journal-id-type="nlm-ta">Cell</journal-id>
<journal-id journal-id-type="iso-abbrev">Cell</journal-id>
<journal-title-group>
<journal-title>Cell</journal-title>
</journal-title-group>
<issn pub-type="ppub">0092-8674</issn>
<issn pub-type="epub">1097-4172</issn>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">29625056</article-id>
<article-id pub-id-type="pmc">5890936</article-id>
<article-id pub-id-type="doi">10.1016/j.cell.2018.03.030</article-id>
<article-id pub-id-type="manuscript">NIHMS952592</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Influenza infection in humans induces broadly cross-reactive and protective neuraminidase-reactive antibodies</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Chen</surname>
<given-names>Yaoqing</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wohlbold</surname>
<given-names>Teddy John</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zheng</surname>
<given-names>Nai-Ying</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Huang</surname>
<given-names>Min</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Huang</surname>
<given-names>Yunping</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Neu</surname>
<given-names>Karlynn E.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lee</surname>
<given-names>Jiwon</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wan</surname>
<given-names>Hongquan</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Rojas</surname>
<given-names>Karla Thatcher</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kirkpatrick</surname>
<given-names>Ericka</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Henry</surname>
<given-names>Carole</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Palm</surname>
<given-names>Anna-Karin E.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Stamper</surname>
<given-names>Christopher T.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lan</surname>
<given-names>Linda Yu-Ling</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Topham</surname>
<given-names>David J.</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Treanor</surname>
<given-names>John</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wrammert</surname>
<given-names>Jens</given-names>
</name>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ahmed</surname>
<given-names>Rafi</given-names>
</name>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Eichelberger</surname>
<given-names>Maryna C.</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Georgiou</surname>
<given-names>George</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Krammer</surname>
<given-names>Florian</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wilson</surname>
<given-names>Patrick C.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref rid="FN2" ref-type="author-notes">9</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
</contrib-group>
<aff id="A1">
<label>1</label>
Department of Medicine, Section of Rheumatology, the Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA</aff>
<aff id="A2">
<label>2</label>
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA</aff>
<aff id="A3">
<label>3</label>
The Committee on Immunology, University of Chicago, Chicago, IL 60637, USA</aff>
<aff id="A4">
<label>4</label>
Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78731, USA</aff>
<aff id="A5">
<label>5</label>
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA</aff>
<aff id="A6">
<label>6</label>
Center for Vaccine Biology & Immunology, Department of Microbiology & Immunology, University of Rochester Medical center, Rochester, NY 14642, USA</aff>
<aff id="A7">
<label>7</label>
Division of Infectious Disease, Department of Medicine, University of Rochester Medical center, Rochester, NY 14642, USA</aff>
<aff id="A8">
<label>8</label>
Emory Vaccine Center, Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322, USA</aff>
<author-notes>
<corresp id="FN1">
<label>*</label>
Correspondence:
<email>florian.krammer@mssm.edu</email>
(F.K.),
<email>wilsonp@uchicago.edu</email>
(P.C.W.)</corresp>
<fn id="FN2">
<label>9</label>
<p>Lead Contact</p>
</fn>
<fn fn-type="COI-statement" id="FN4">
<p>
<bold>DECLARATION OF INTERESTS</bold>
</p>
<p>The authors declare no competing interests.</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted">
<day>20</day>
<month>3</month>
<year>2018</year>
</pub-date>
<pub-date pub-type="ppub">
<day>05</day>
<month>4</month>
<year>2018</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>05</day>
<month>4</month>
<year>2019</year>
</pub-date>
<volume>173</volume>
<issue>2</issue>
<fpage>417</fpage>
<lpage>429.e10</lpage>
<pmc-comment>elocation-id from pubmed: 10.1016/j.cell.2018.03.030</pmc-comment>
<abstract id="Abs1">
<title>SUMMARY</title>
<p id="P1">Antibodies to the hemagglutinin (HA) and neuraminidase (NA) glycoproteins are the major mediators of protection against influenza virus infection. Here, we report that current influenza vaccines poorly display key NA epitopes and rarely induce NA-reactive B cells. Conversely, influenza virus infection induces NA-reactive B cells at a frequency that approaches (H1N1) or exceeds (H3N2) that of HA-reactive B cells. NA-reactive antibodies display broad binding activity spanning the entire history of influenza A virus circulation in humans, including the original pandemic strains of both H1N1 and H3N2 subtypes. The antibodies robustly inhibit the enzymatic activity of NA, including oseltamivir-resistant variants, and provide robust prophylactic protection
<italic>in vivo</italic>
, including against avian H5N1 viruses. When used therapeutically, NA-reactive antibodies protected mice from lethal influenza virus challenge even 48-hours post-infection. These findings strongly suggest that influenza vaccines should be optimized to improve targeting of NA for durable and broad protection against divergent influenza strains.</p>
</abstract>
<abstract abstract-type="graphical" id="Abs2">
<title>In Brief</title>
<p id="P2">Current influenza vaccines predominantly produce antibodies targeting the viral hemagglutinin (HA). However, during natural infection the body also produces antibodies targeting the viral neuraminidase (NA). These NA antibodies can provide robust and broad protection and could potentially be elicited prophylactically, via new vaccine strategies, or used therapeutically.</p>
<p id="P3">
<graphic xlink:href="nihms952592u1.jpg" position="anchor" orientation="portrait"></graphic>
</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>

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