Influenza Virus Vaccine Based on the Conserved Hemagglutinin Stalk Domain
Identifieur interne : 000554 ( Ncbi/Merge ); précédent : 000553; suivant : 000555Influenza Virus Vaccine Based on the Conserved Hemagglutinin Stalk Domain
Auteurs : John Steel ; Anice C. Lowen ; Taia T. Wang ; Mark Yondola ; Qinshan Gao ; Kester Haye ; Adolfo García-Sastre ; Peter PaleseSource :
- mBio [ 2150-7511 ] ; 2010.
Abstract
Although highly effective in the general population when well matched to circulating influenza virus strains, current influenza vaccines are limited in their utility due to the narrow breadth of protection they provide. The strain specificity of vaccines presently in use mirrors the exquisite specificity of the neutralizing antibodies that they induce, that is, antibodies which bind to the highly variable globular head domain of hemagglutinin (HA). Herein, we describe the construction of a novel immunogen comprising the conserved influenza HA stalk domain and lacking the globular head. Vaccination of mice with this headless HA construct elicited immune sera with broader reactivity than those obtained from mice immunized with a full-length HA. Furthermore, the headless HA vaccine provided full protection against death and partial protection against disease following lethal viral challenge. Our results suggest that the response induced by headless HA vaccines is sufficiently potent to warrant their further development toward a universal influenza virus vaccine.
Url:
DOI: 10.1128/mBio.00018-10
PubMed: 20689752
PubMed Central: 2912658
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PMC:2912658Le document en format XML
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Wang</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Yondola, Mark" sort="Yondola, Mark" uniqKey="Yondola M" first="Mark" last="Yondola">Mark Yondola</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Gao, Qinshan" sort="Gao, Qinshan" uniqKey="Gao Q" first="Qinshan" last="Gao">Qinshan Gao</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Haye, Kester" sort="Haye, Kester" uniqKey="Haye K" first="Kester" last="Haye">Kester Haye</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="García-Sastre">Adolfo García-Sastre</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Palese, Peter" sort="Palese, Peter" uniqKey="Palese P" first="Peter" last="Palese">Peter Palese</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20689752</idno><idno type="pmc">2912658</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912658</idno><idno type="RBID">PMC:2912658</idno><idno type="doi">10.1128/mBio.00018-10</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">000C59</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000C59</idno><idno type="wicri:Area/Pmc/Curation">000C59</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000C59</idno><idno type="wicri:Area/Pmc/Checkpoint">000930</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000930</idno><idno type="wicri:Area/Ncbi/Merge">000554</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Influenza Virus Vaccine Based on the Conserved Hemagglutinin Stalk Domain</title><author><name sortKey="Steel, John" sort="Steel, John" uniqKey="Steel J" first="John" last="Steel">John Steel</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Lowen, Anice C" sort="Lowen, Anice C" uniqKey="Lowen A" first="Anice C." last="Lowen">Anice C. Lowen</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Wang, Taia T" sort="Wang, Taia T" uniqKey="Wang T" first="Taia T." last="Wang">Taia T. Wang</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Yondola, Mark" sort="Yondola, Mark" uniqKey="Yondola M" first="Mark" last="Yondola">Mark Yondola</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Gao, Qinshan" sort="Gao, Qinshan" uniqKey="Gao Q" first="Qinshan" last="Gao">Qinshan Gao</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Haye, Kester" sort="Haye, Kester" uniqKey="Haye K" first="Kester" last="Haye">Kester Haye</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="García-Sastre">Adolfo García-Sastre</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Palese, Peter" sort="Palese, Peter" uniqKey="Palese P" first="Peter" last="Palese">Peter Palese</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author></analytic><series><title level="j">mBio</title><idno type="eISSN">2150-7511</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>ABSTRACT</title><p>Although highly effective in the general population when well matched to circulating influenza virus strains, current influenza vaccines are limited in their utility due to the narrow breadth of protection they provide. The strain specificity of vaccines presently in use mirrors the exquisite specificity of the neutralizing antibodies that they induce, that is, antibodies which bind to the highly variable globular head domain of hemagglutinin (HA). Herein, we describe the construction of a novel immunogen comprising the conserved influenza HA stalk domain and lacking the globular head. Vaccination of mice with this headless HA construct elicited immune sera with broader reactivity than those obtained from mice immunized with a full-length HA. Furthermore, the headless HA vaccine provided full protection against death and partial protection against disease following lethal viral challenge. Our results suggest that the response induced by headless HA vaccines is sufficiently potent to warrant their further development toward a universal influenza virus vaccine.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Fox, J P" uniqKey="Fox J">J. P. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">mBio</journal-id><journal-id journal-id-type="iso-abbrev">MBio</journal-id><journal-id journal-id-type="hwp">mbio</journal-id><journal-id journal-id-type="pmc">mbio</journal-id><journal-id journal-id-type="publisher-id">mBio</journal-id><journal-title-group><journal-title>mBio</journal-title></journal-title-group><issn pub-type="epub">2150-7511</issn><publisher><publisher-name>American Society of Microbiology</publisher-name><publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">20689752</article-id><article-id pub-id-type="pmc">2912658</article-id><article-id pub-id-type="publisher-id">mBio00018-10</article-id><article-id pub-id-type="doi">10.1128/mBio.00018-10</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Influenza Virus Vaccine Based on the Conserved Hemagglutinin Stalk Domain</article-title><alt-title>Headless HA Influenza Vaccine</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Steel</surname><given-names>John</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lowen</surname><given-names>Anice C.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Taia T.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Yondola</surname><given-names>Mark</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gao</surname><given-names>Qinshan</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Haye</surname><given-names>Kester</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>García-Sastre</surname><given-names>Adolfo</given-names></name><xref ref-type="aff" rid="aff1"><sup>a,</sup></xref><xref ref-type="aff" rid="aff2"><sup>b,</sup></xref><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Palese</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="aff1"><sup>a,</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><aff id="aff1">Department of Microbiology,<label><sup>a</sup></label></aff><aff id="aff2">Department of Medicine, Division of Infectious Diseases,<label><sup>b</sup></label> and</aff><aff id="aff3">Emerging Pathogens Institute,<label><sup>c</sup></label> Mount Sinai School of Medicine, New York, New York, USA</aff></contrib-group><author-notes><corresp id="cor1">Address correspondence to Peter Palese, <email>peter.palese@mssm.edu</email>.</corresp><fn fn-type="equal"><p>John Steel and Anice C. Lowen contributed equally to this article.</p></fn><fn fn-type="edited-by"><p><bold>Editor</bold> Terence Dermody, Vanderbilt University Medical Center</p></fn></author-notes><pub-date pub-type="epub"><day>18</day><month>5</month><year>2010</year></pub-date><pub-date pub-type="collection"><month>4</month><year>2010</year></pub-date><volume>1</volume><issue>1</issue><elocation-id>e00018-10</elocation-id><history><date date-type="received"><day>28</day><month>1</month><year>2010</year></date><date date-type="accepted"><day>29</day><month>1</month><year>2010</year></date></history><permissions><copyright-statement>Copyright © 2010 Steel et al. </copyright-statement><copyright-year>2010</copyright-year><copyright-holder>Steel et al.</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-sa/3.0/"><license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc-sa/3.0/">Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License</ext-link>, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><abstract><title>ABSTRACT</title><p>Although highly effective in the general population when well matched to circulating influenza virus strains, current influenza vaccines are limited in their utility due to the narrow breadth of protection they provide. The strain specificity of vaccines presently in use mirrors the exquisite specificity of the neutralizing antibodies that they induce, that is, antibodies which bind to the highly variable globular head domain of hemagglutinin (HA). Herein, we describe the construction of a novel immunogen comprising the conserved influenza HA stalk domain and lacking the globular head. Vaccination of mice with this headless HA construct elicited immune sera with broader reactivity than those obtained from mice immunized with a full-length HA. Furthermore, the headless HA vaccine provided full protection against death and partial protection against disease following lethal viral challenge. Our results suggest that the response induced by headless HA vaccines is sufficiently potent to warrant their further development toward a universal influenza virus vaccine.</p></abstract><abstract abstract-type="executive-summary"><title>IMPORTANCE</title><p> Current influenza vaccines are effective against only a narrow range of influenza virus strains. It is for this reason that new vaccines must be generated and administered each year. We now report progress toward the goal of an influenza virus vaccine which would protect against multiple strains. Our approach is based on presentation to the host immune system of a region of the influenza virus—called a “headless hemagglutinin” (headless HA)—which is similar among a multitude of diverse strains. We show that vaccination of mice with a headless HA confers protection to these animals against a lethal influenza virus challenge, thereby demonstrating the viability of the approach. Through further development and testing, we predict that a single immunization with a headless HA vaccine will offer effective protection through several influenza epidemics.</p></abstract></article-meta></front></pmc><affiliations><list></list><tree><noCountry><name sortKey="Gao, Qinshan" sort="Gao, Qinshan" uniqKey="Gao Q" first="Qinshan" last="Gao">Qinshan Gao</name><name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="García-Sastre">Adolfo García-Sastre</name><name sortKey="Haye, Kester" sort="Haye, Kester" uniqKey="Haye K" first="Kester" last="Haye">Kester Haye</name><name sortKey="Lowen, Anice C" sort="Lowen, Anice C" uniqKey="Lowen A" first="Anice C." last="Lowen">Anice C. Lowen</name><name sortKey="Palese, Peter" sort="Palese, Peter" uniqKey="Palese P" first="Peter" last="Palese">Peter Palese</name><name sortKey="Steel, John" sort="Steel, John" uniqKey="Steel J" first="John" last="Steel">John Steel</name><name sortKey="Wang, Taia T" sort="Wang, Taia T" uniqKey="Wang T" first="Taia T." last="Wang">Taia T. Wang</name><name sortKey="Yondola, Mark" sort="Yondola, Mark" uniqKey="Yondola M" first="Mark" last="Yondola">Mark Yondola</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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