Antibody recognition of a highly conserved influenza virus epitope: implications for universal prevention and therapy
Identifieur interne : 000C53 ( Pmc/Checkpoint ); précédent : 000C52; suivant : 000C54Antibody recognition of a highly conserved influenza virus epitope: implications for universal prevention and therapy
Auteurs : Damian C. Ekiert [États-Unis] ; Gira Bhabha [États-Unis] ; Marc-André Elsliger [États-Unis] ; Robert H. E. Friesen [Pays-Bas] ; Mandy Jongeneelen [Pays-Bas] ; Mark Throsby [Pays-Bas] ; Jaap Goudsmit [Pays-Bas] ; Ian A. Wilson [États-Unis]Source :
- Science (New York, N.Y.) [ 0036-8075 ] ; 2009.
Abstract
Influenza virus presents a significant and persistent threat to public health worldwide and current vaccines provide immunity to viral isolates similar to the vaccine strain. High affinity antibodies against a conserved epitope could provide immunity to the diverse influenza subtypes and protection against future pandemic viruses. Co-crystal structures were determined at 2.2 and 2.7 Å resolutions for broadly neutralizing human antibody CR6261 Fab in complexes with the major surface antigen (hemagglutinin, HA) from viruses responsible for the 1918 H1N1 influenza pandemic and a recent lethal case of H5N1 avian influenza. In contrast to all other structurally characterized influenza antibodies, CR6261 recognizes a highly conserved helical region in the membrane-proximal stem of HA1/HA2. The antibody neutralizes the virus by blocking conformational rearrangements associated with membrane fusion. The CR6261 epitope identified here should accelerate the design and implementation of improved vaccines that can elicit CR6261-like antibodies, as well as antibody-based therapies for the treatment of influenza.
Url:
DOI: 10.1126/science.1171491
PubMed: 19251591
PubMed Central: 2758658
Affiliations:
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Ekiert</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Bhabha, Gira" sort="Bhabha, Gira" uniqKey="Bhabha G" first="Gira" last="Bhabha">Gira Bhabha</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Elsliger, Marc Andre" sort="Elsliger, Marc Andre" uniqKey="Elsliger M" first="Marc-André" last="Elsliger">Marc-André Elsliger</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Friesen, Robert H E" sort="Friesen, Robert H E" uniqKey="Friesen R" first="Robert H. E." last="Friesen">Robert H. E. Friesen</name><affiliation wicri:level="1"><nlm:aff id="A2">Crucell Holland BV, Archimedesweg 4–6, 2301 CA Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Crucell Holland BV, Archimedesweg 4–6, 2301 CA Leiden</wicri:regionArea><wicri:noRegion>2301 CA Leiden</wicri:noRegion></affiliation></author><author><name sortKey="Jongeneelen, Mandy" sort="Jongeneelen, Mandy" uniqKey="Jongeneelen M" first="Mandy" last="Jongeneelen">Mandy Jongeneelen</name><affiliation wicri:level="1"><nlm:aff id="A2">Crucell Holland BV, Archimedesweg 4–6, 2301 CA Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Crucell Holland BV, Archimedesweg 4–6, 2301 CA Leiden</wicri:regionArea><wicri:noRegion>2301 CA Leiden</wicri:noRegion></affiliation></author><author><name sortKey="Throsby, Mark" sort="Throsby, Mark" uniqKey="Throsby M" first="Mark" last="Throsby">Mark Throsby</name><affiliation wicri:level="1"><nlm:aff id="A2">Crucell Holland BV, Archimedesweg 4–6, 2301 CA Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Crucell Holland BV, Archimedesweg 4–6, 2301 CA Leiden</wicri:regionArea><wicri:noRegion>2301 CA Leiden</wicri:noRegion></affiliation></author><author><name sortKey="Goudsmit, Jaap" sort="Goudsmit, Jaap" uniqKey="Goudsmit J" first="Jaap" last="Goudsmit">Jaap Goudsmit</name><affiliation wicri:level="1"><nlm:aff id="A2">Crucell Holland BV, Archimedesweg 4–6, 2301 CA Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Crucell Holland BV, Archimedesweg 4–6, 2301 CA Leiden</wicri:regionArea><wicri:noRegion>2301 CA Leiden</wicri:noRegion></affiliation></author><author><name sortKey="Wilson, Ian A" sort="Wilson, Ian A" uniqKey="Wilson I" first="Ian A." last="Wilson">Ian A. Wilson</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A3">The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author></analytic><series><title level="j">Science (New York, N.Y.)</title><idno type="ISSN">0036-8075</idno><idno type="eISSN">1095-9203</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Influenza virus presents a significant and persistent threat to public health worldwide and current vaccines provide immunity to viral isolates similar to the vaccine strain. High affinity antibodies against a conserved epitope could provide immunity to the diverse influenza subtypes and protection against future pandemic viruses. Co-crystal structures were determined at 2.2 and 2.7 Å resolutions for broadly neutralizing human antibody CR6261 Fab in complexes with the major surface antigen (hemagglutinin, HA) from viruses responsible for the 1918 H1N1 influenza pandemic and a recent lethal case of H5N1 avian influenza. In contrast to all other structurally characterized influenza antibodies, CR6261 recognizes a highly conserved helical region in the membrane-proximal stem of HA1/HA2. The antibody neutralizes the virus by blocking conformational rearrangements associated with membrane fusion. The CR6261 epitope identified here should accelerate the design and implementation of improved vaccines that can elicit CR6261-like antibodies, as well as antibody-based therapies for the treatment of influenza.</p></div></front></TEI><pmc article-type="research-article" xml:lang="EN"><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">0404511</journal-id><journal-id journal-id-type="pubmed-jr-id">7473</journal-id><journal-id journal-id-type="nlm-ta">Science</journal-id><journal-title>Science (New York, N.Y.)</journal-title><issn pub-type="ppub">0036-8075</issn><issn pub-type="epub">1095-9203</issn></journal-meta><article-meta><article-id pub-id-type="pmid">19251591</article-id><article-id pub-id-type="pmc">2758658</article-id><article-id pub-id-type="doi">10.1126/science.1171491</article-id><article-id pub-id-type="manuscript">NIHMS121423</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Antibody recognition of a highly conserved influenza virus epitope: implications for universal prevention and therapy</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Ekiert</surname><given-names>Damian C.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Bhabha</surname><given-names>Gira</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Elsliger</surname><given-names>Marc-André</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Friesen</surname><given-names>Robert H. E.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Jongeneelen</surname><given-names>Mandy</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Throsby</surname><given-names>Mark</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Goudsmit</surname><given-names>Jaap</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Wilson</surname><given-names>Ian A.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A3">3</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.</aff><aff id="A2"><label>2</label>Crucell Holland BV, Archimedesweg 4–6, 2301 CA Leiden, The Netherlands</aff><aff id="A3"><label>3</label>The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.</aff><author-notes><corresp id="cor1"><label>*</label>To whom correspondence should be addressed. E-mail: <email>wilson@scripps.edu</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>12</day><month>6</month><year>2009</year></pub-date><pub-date pub-type="epub"><day>26</day><month>2</month><year>2009</year></pub-date><pub-date pub-type="ppub"><day>10</day><month>4</month><year>2009</year></pub-date><pub-date pub-type="pmc-release"><day>10</day><month>4</month><year>2010</year></pub-date><volume>324</volume><issue>5924</issue><fpage>246</fpage><lpage>251</lpage><abstract><p id="P1">Influenza virus presents a significant and persistent threat to public health worldwide and current vaccines provide immunity to viral isolates similar to the vaccine strain. High affinity antibodies against a conserved epitope could provide immunity to the diverse influenza subtypes and protection against future pandemic viruses. Co-crystal structures were determined at 2.2 and 2.7 Å resolutions for broadly neutralizing human antibody CR6261 Fab in complexes with the major surface antigen (hemagglutinin, HA) from viruses responsible for the 1918 H1N1 influenza pandemic and a recent lethal case of H5N1 avian influenza. In contrast to all other structurally characterized influenza antibodies, CR6261 recognizes a highly conserved helical region in the membrane-proximal stem of HA1/HA2. The antibody neutralizes the virus by blocking conformational rearrangements associated with membrane fusion. The CR6261 epitope identified here should accelerate the design and implementation of improved vaccines that can elicit CR6261-like antibodies, as well as antibody-based therapies for the treatment of influenza.</p></abstract><contract-num rid="GM1">U54 GM074898-03
||GM</contract-num><contract-num rid="AI1">P01 AI058113-040002
||AI</contract-num><contract-sponsor id="GM1">National Institute of General Medical Sciences : NIGMS</contract-sponsor><contract-sponsor id="AI1">National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID</contract-sponsor></article-meta></front></pmc><affiliations><list><country><li>Pays-Bas</li><li>États-Unis</li></country><region><li>Californie</li></region></list><tree><country name="États-Unis"><region name="Californie"><name sortKey="Ekiert, Damian C" sort="Ekiert, Damian C" uniqKey="Ekiert D" first="Damian C." last="Ekiert">Damian C. Ekiert</name></region><name sortKey="Bhabha, Gira" sort="Bhabha, Gira" uniqKey="Bhabha G" first="Gira" last="Bhabha">Gira Bhabha</name><name sortKey="Elsliger, Marc Andre" sort="Elsliger, Marc Andre" uniqKey="Elsliger M" first="Marc-André" last="Elsliger">Marc-André Elsliger</name><name sortKey="Wilson, Ian A" sort="Wilson, Ian A" uniqKey="Wilson I" first="Ian A." last="Wilson">Ian A. Wilson</name><name sortKey="Wilson, Ian A" sort="Wilson, Ian A" uniqKey="Wilson I" first="Ian A." last="Wilson">Ian A. Wilson</name></country><country name="Pays-Bas"><noRegion><name sortKey="Friesen, Robert H E" sort="Friesen, Robert H E" uniqKey="Friesen R" first="Robert H. E." last="Friesen">Robert H. E. Friesen</name></noRegion><name sortKey="Goudsmit, Jaap" sort="Goudsmit, Jaap" uniqKey="Goudsmit J" first="Jaap" last="Goudsmit">Jaap Goudsmit</name><name sortKey="Jongeneelen, Mandy" sort="Jongeneelen, Mandy" uniqKey="Jongeneelen M" first="Mandy" last="Jongeneelen">Mandy Jongeneelen</name><name sortKey="Throsby, Mark" sort="Throsby, Mark" uniqKey="Throsby M" first="Mark" last="Throsby">Mark Throsby</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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