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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Antibody recognition of a highly conserved influenza virus epitope: implications for universal prevention and therapy</title><author><name sortKey="Ekiert, Damian C" sort="Ekiert, Damian C" uniqKey="Ekiert D" first="Damian C." last="Ekiert">Damian C. Ekiert</name><affiliation><nlm:aff id="A1">Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.</nlm:aff></affiliation></author><author><name sortKey="Bhabha, Gira" sort="Bhabha, Gira" uniqKey="Bhabha G" first="Gira" last="Bhabha">Gira Bhabha</name><affiliation><nlm:aff id="A1">Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.</nlm:aff></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><nlm:aff id="A1">Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.</nlm:aff></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><nlm:aff id="A2">Crucell Holland BV, Archimedesweg 4–6, 2301 CA Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Jongeneelen, Mandy" sort="Jongeneelen, Mandy" uniqKey="Jongeneelen M" first="Mandy" last="Jongeneelen">Mandy Jongeneelen</name><affiliation><nlm:aff id="A2">Crucell Holland BV, Archimedesweg 4–6, 2301 CA Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Throsby, Mark" sort="Throsby, Mark" uniqKey="Throsby M" first="Mark" last="Throsby">Mark Throsby</name><affiliation><nlm:aff id="A2">Crucell Holland BV, Archimedesweg 4–6, 2301 CA Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Goudsmit, Jaap" sort="Goudsmit, Jaap" uniqKey="Goudsmit J" first="Jaap" last="Goudsmit">Jaap Goudsmit</name><affiliation><nlm:aff id="A2">Crucell Holland BV, Archimedesweg 4–6, 2301 CA Leiden, The Netherlands</nlm:aff></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><nlm:aff id="A1">Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.</nlm:aff></affiliation><affiliation><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></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19251591</idno><idno type="pmc">2758658</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758658</idno><idno type="RBID">PMC:2758658</idno><idno type="doi">10.1126/science.1171491</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">000527</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000527</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Antibody recognition of a highly conserved influenza virus epitope: implications for universal prevention and therapy</title><author><name sortKey="Ekiert, Damian C" sort="Ekiert, Damian C" uniqKey="Ekiert D" first="Damian C." last="Ekiert">Damian C. Ekiert</name><affiliation><nlm:aff id="A1">Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.</nlm:aff></affiliation></author><author><name sortKey="Bhabha, Gira" sort="Bhabha, Gira" uniqKey="Bhabha G" first="Gira" last="Bhabha">Gira Bhabha</name><affiliation><nlm:aff id="A1">Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.</nlm:aff></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><nlm:aff id="A1">Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.</nlm:aff></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><nlm:aff id="A2">Crucell Holland BV, Archimedesweg 4–6, 2301 CA Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Jongeneelen, Mandy" sort="Jongeneelen, Mandy" uniqKey="Jongeneelen M" first="Mandy" last="Jongeneelen">Mandy Jongeneelen</name><affiliation><nlm:aff id="A2">Crucell Holland BV, Archimedesweg 4–6, 2301 CA Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Throsby, Mark" sort="Throsby, Mark" uniqKey="Throsby M" first="Mark" last="Throsby">Mark Throsby</name><affiliation><nlm:aff id="A2">Crucell Holland BV, Archimedesweg 4–6, 2301 CA Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Goudsmit, Jaap" sort="Goudsmit, Jaap" uniqKey="Goudsmit J" first="Jaap" last="Goudsmit">Jaap Goudsmit</name><affiliation><nlm:aff id="A2">Crucell Holland BV, Archimedesweg 4–6, 2301 CA Leiden, The Netherlands</nlm:aff></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><nlm:aff id="A1">Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.</nlm:aff></affiliation><affiliation><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></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></record>Pour manipuler ce document sous Unix (Dilib)
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