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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Influenza immunization elicits antibodies specific for an egg-adapted vaccine strain</title><author><name sortKey="Raymond, Donald D" sort="Raymond, Donald D" uniqKey="Raymond D" first="Donald D" last="Raymond">Donald D. Raymond</name><affiliation><nlm:aff id="A1">Laboratory of Molecular Medicine, Boston Children’s Hospital, Harvard Medical School</nlm:aff></affiliation></author><author><name sortKey="Stewart, Shaun M" sort="Stewart, Shaun M" uniqKey="Stewart S" first="Shaun M" last="Stewart">Shaun M. Stewart</name><affiliation><nlm:aff id="A2">Seqirus, 45 Sidney St., Cambridge, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Lee, Jiwon" sort="Lee, Jiwon" uniqKey="Lee J" first="Jiwon" last="Lee">Jiwon Lee</name><affiliation><nlm:aff id="A3">Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA</nlm:aff></affiliation></author><author><name sortKey="Ferdman, Jack" sort="Ferdman, Jack" uniqKey="Ferdman J" first="Jack" last="Ferdman">Jack Ferdman</name><affiliation><nlm:aff id="A2">Seqirus, 45 Sidney St., Cambridge, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Bajic, Goran" sort="Bajic, Goran" uniqKey="Bajic G" first="Goran" last="Bajic">Goran Bajic</name><affiliation><nlm:aff id="A1">Laboratory of Molecular Medicine, Boston Children’s Hospital, Harvard Medical School</nlm:aff></affiliation></author><author><name sortKey="Do, Khoi T" sort="Do, Khoi T" uniqKey="Do K" first="Khoi T" last="Do">Khoi T. Do</name><affiliation><nlm:aff id="A1">Laboratory of Molecular Medicine, Boston Children’s Hospital, Harvard Medical School</nlm:aff></affiliation></author><author><name sortKey="Ernandes, Michael J" sort="Ernandes, Michael J" uniqKey="Ernandes M" first="Michael J" last="Ernandes">Michael J. Ernandes</name><affiliation><nlm:aff id="A1">Laboratory of Molecular Medicine, Boston Children’s Hospital, Harvard Medical School</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Graduate Program in Virology, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Suphaphiphat, Pirada" sort="Suphaphiphat, Pirada" uniqKey="Suphaphiphat P" first="Pirada" last="Suphaphiphat">Pirada Suphaphiphat</name><affiliation><nlm:aff id="A2">Seqirus, 45 Sidney St., Cambridge, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Settembre, Ethan C" sort="Settembre, Ethan C" uniqKey="Settembre E" first="Ethan C" last="Settembre">Ethan C. Settembre</name><affiliation><nlm:aff id="A2">Seqirus, 45 Sidney St., Cambridge, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Dormitzer, Philip R" sort="Dormitzer, Philip R" uniqKey="Dormitzer P" first="Philip R" last="Dormitzer">Philip R. Dormitzer</name><affiliation><nlm:aff id="A2">Seqirus, 45 Sidney St., Cambridge, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Giudice, Giuseppe Del" sort="Giudice, Giuseppe Del" uniqKey="Giudice G" first="Giuseppe Del" last="Giudice">Giuseppe Del Giudice</name><affiliation><nlm:aff id="A5">Novartis Vaccines and Diagnostics, Siena, Italy</nlm:aff></affiliation></author><author><name sortKey="Finco, Oretta" sort="Finco, Oretta" uniqKey="Finco O" first="Oretta" last="Finco">Oretta Finco</name><affiliation><nlm:aff id="A5">Novartis Vaccines and Diagnostics, Siena, Italy</nlm:aff></affiliation></author><author><name sortKey="Kang, Tae Hyun" sort="Kang, Tae Hyun" uniqKey="Kang T" first="Tae Hyun" last="Kang">Tae Hyun Kang</name><affiliation><nlm:aff id="A3">Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA</nlm:aff></affiliation></author><author><name sortKey="Ippolito, Gregory C" sort="Ippolito, Gregory C" uniqKey="Ippolito G" first="Gregory C" last="Ippolito">Gregory C. Ippolito</name><affiliation><nlm:aff id="A6">Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA</nlm:aff></affiliation></author><author><name sortKey="Georgiou, George" sort="Georgiou, George" uniqKey="Georgiou G" first="George" last="Georgiou">George Georgiou</name><affiliation><nlm:aff id="A3">Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Center of Systems and Synthetic Biology, University of Texas at Austin, Austin, Texas, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A8">Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, USA</nlm:aff></affiliation></author><author><name sortKey="Kepler, Thomas B" sort="Kepler, Thomas B" uniqKey="Kepler T" first="Thomas B" last="Kepler">Thomas B. Kepler</name><affiliation><nlm:aff id="A9">Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Haynes, Barton F" sort="Haynes, Barton F" uniqKey="Haynes B" first="Barton F" last="Haynes">Barton F. Haynes</name><affiliation><nlm:aff id="A10">Duke Human Vaccine Institute, Duke University Medical School, Durham, North Carolina, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A11">Department of Medicine, Duke University Medical School, Durham, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Moody, M Anthony" sort="Moody, M Anthony" uniqKey="Moody M" first="M Anthony" last="Moody">M Anthony Moody</name><affiliation><nlm:aff id="A10">Duke Human Vaccine Institute, Duke University Medical School, Durham, North Carolina, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Department of Pediatrics, Duke University Medical School, Durham, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Liao, Hua Xin" sort="Liao, Hua Xin" uniqKey="Liao H" first="Hua-Xin" last="Liao">Hua-Xin Liao</name><affiliation><nlm:aff id="A10">Duke Human Vaccine Institute, Duke University Medical School, Durham, North Carolina, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A11">Department of Medicine, Duke University Medical School, Durham, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Schmidt, Aaron G" sort="Schmidt, Aaron G" uniqKey="Schmidt A" first="Aaron G" last="Schmidt">Aaron G. Schmidt</name><affiliation><nlm:aff id="A1">Laboratory of Molecular Medicine, Boston Children’s Hospital, Harvard Medical School</nlm:aff></affiliation></author><author><name sortKey="Harrison, Stephen C" sort="Harrison, Stephen C" uniqKey="Harrison S" first="Stephen C" last="Harrison">Stephen C. Harrison</name><affiliation><nlm:aff id="A1">Laboratory of Molecular Medicine, Boston Children’s Hospital, Harvard Medical School</nlm:aff></affiliation><affiliation><nlm:aff id="A13">Howard Hughes Medical Institute, Boston, Massachusetts, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27820604</idno><idno type="pmc">5485662</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485662</idno><idno type="RBID">PMC:5485662</idno><idno type="doi">10.1038/nm.4223</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000884</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000884</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Influenza immunization elicits antibodies specific for an egg-adapted vaccine strain</title><author><name sortKey="Raymond, Donald D" sort="Raymond, Donald D" uniqKey="Raymond D" first="Donald D" last="Raymond">Donald D. Raymond</name><affiliation><nlm:aff id="A1">Laboratory of Molecular Medicine, Boston Children’s Hospital, Harvard Medical School</nlm:aff></affiliation></author><author><name sortKey="Stewart, Shaun M" sort="Stewart, Shaun M" uniqKey="Stewart S" first="Shaun M" last="Stewart">Shaun M. Stewart</name><affiliation><nlm:aff id="A2">Seqirus, 45 Sidney St., Cambridge, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Lee, Jiwon" sort="Lee, Jiwon" uniqKey="Lee J" first="Jiwon" last="Lee">Jiwon Lee</name><affiliation><nlm:aff id="A3">Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA</nlm:aff></affiliation></author><author><name sortKey="Ferdman, Jack" sort="Ferdman, Jack" uniqKey="Ferdman J" first="Jack" last="Ferdman">Jack Ferdman</name><affiliation><nlm:aff id="A2">Seqirus, 45 Sidney St., Cambridge, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Bajic, Goran" sort="Bajic, Goran" uniqKey="Bajic G" first="Goran" last="Bajic">Goran Bajic</name><affiliation><nlm:aff id="A1">Laboratory of Molecular Medicine, Boston Children’s Hospital, Harvard Medical School</nlm:aff></affiliation></author><author><name sortKey="Do, Khoi T" sort="Do, Khoi T" uniqKey="Do K" first="Khoi T" last="Do">Khoi T. Do</name><affiliation><nlm:aff id="A1">Laboratory of Molecular Medicine, Boston Children’s Hospital, Harvard Medical School</nlm:aff></affiliation></author><author><name sortKey="Ernandes, Michael J" sort="Ernandes, Michael J" uniqKey="Ernandes M" first="Michael J" last="Ernandes">Michael J. Ernandes</name><affiliation><nlm:aff id="A1">Laboratory of Molecular Medicine, Boston Children’s Hospital, Harvard Medical School</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Graduate Program in Virology, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Suphaphiphat, Pirada" sort="Suphaphiphat, Pirada" uniqKey="Suphaphiphat P" first="Pirada" last="Suphaphiphat">Pirada Suphaphiphat</name><affiliation><nlm:aff id="A2">Seqirus, 45 Sidney St., Cambridge, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Settembre, Ethan C" sort="Settembre, Ethan C" uniqKey="Settembre E" first="Ethan C" last="Settembre">Ethan C. Settembre</name><affiliation><nlm:aff id="A2">Seqirus, 45 Sidney St., Cambridge, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Dormitzer, Philip R" sort="Dormitzer, Philip R" uniqKey="Dormitzer P" first="Philip R" last="Dormitzer">Philip R. Dormitzer</name><affiliation><nlm:aff id="A2">Seqirus, 45 Sidney St., Cambridge, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Giudice, Giuseppe Del" sort="Giudice, Giuseppe Del" uniqKey="Giudice G" first="Giuseppe Del" last="Giudice">Giuseppe Del Giudice</name><affiliation><nlm:aff id="A5">Novartis Vaccines and Diagnostics, Siena, Italy</nlm:aff></affiliation></author><author><name sortKey="Finco, Oretta" sort="Finco, Oretta" uniqKey="Finco O" first="Oretta" last="Finco">Oretta Finco</name><affiliation><nlm:aff id="A5">Novartis Vaccines and Diagnostics, Siena, Italy</nlm:aff></affiliation></author><author><name sortKey="Kang, Tae Hyun" sort="Kang, Tae Hyun" uniqKey="Kang T" first="Tae Hyun" last="Kang">Tae Hyun Kang</name><affiliation><nlm:aff id="A3">Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA</nlm:aff></affiliation></author><author><name sortKey="Ippolito, Gregory C" sort="Ippolito, Gregory C" uniqKey="Ippolito G" first="Gregory C" last="Ippolito">Gregory C. Ippolito</name><affiliation><nlm:aff id="A6">Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA</nlm:aff></affiliation></author><author><name sortKey="Georgiou, George" sort="Georgiou, George" uniqKey="Georgiou G" first="George" last="Georgiou">George Georgiou</name><affiliation><nlm:aff id="A3">Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Center of Systems and Synthetic Biology, University of Texas at Austin, Austin, Texas, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A8">Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, USA</nlm:aff></affiliation></author><author><name sortKey="Kepler, Thomas B" sort="Kepler, Thomas B" uniqKey="Kepler T" first="Thomas B" last="Kepler">Thomas B. Kepler</name><affiliation><nlm:aff id="A9">Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Haynes, Barton F" sort="Haynes, Barton F" uniqKey="Haynes B" first="Barton F" last="Haynes">Barton F. Haynes</name><affiliation><nlm:aff id="A10">Duke Human Vaccine Institute, Duke University Medical School, Durham, North Carolina, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A11">Department of Medicine, Duke University Medical School, Durham, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Moody, M Anthony" sort="Moody, M Anthony" uniqKey="Moody M" first="M Anthony" last="Moody">M Anthony Moody</name><affiliation><nlm:aff id="A10">Duke Human Vaccine Institute, Duke University Medical School, Durham, North Carolina, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Department of Pediatrics, Duke University Medical School, Durham, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Liao, Hua Xin" sort="Liao, Hua Xin" uniqKey="Liao H" first="Hua-Xin" last="Liao">Hua-Xin Liao</name><affiliation><nlm:aff id="A10">Duke Human Vaccine Institute, Duke University Medical School, Durham, North Carolina, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A11">Department of Medicine, Duke University Medical School, Durham, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Schmidt, Aaron G" sort="Schmidt, Aaron G" uniqKey="Schmidt A" first="Aaron G" last="Schmidt">Aaron G. Schmidt</name><affiliation><nlm:aff id="A1">Laboratory of Molecular Medicine, Boston Children’s Hospital, Harvard Medical School</nlm:aff></affiliation></author><author><name sortKey="Harrison, Stephen C" sort="Harrison, Stephen C" uniqKey="Harrison S" first="Stephen C" last="Harrison">Stephen C. Harrison</name><affiliation><nlm:aff id="A1">Laboratory of Molecular Medicine, Boston Children’s Hospital, Harvard Medical School</nlm:aff></affiliation><affiliation><nlm:aff id="A13">Howard Hughes Medical Institute, Boston, Massachusetts, USA</nlm:aff></affiliation></author></analytic><series><title level="j">Nature medicine</title><idno type="ISSN">1078-8956</idno><idno type="eISSN">1546-170X</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">For broad protection against infection by viruses such as influenza or HIV, vaccines should elicit antibodies that bind conserved viral epitopes, such as the receptor-binding site (RBS). RBS-directed antibodies have been described for both HIV<sup><xref rid="R1" ref-type="bibr">1</xref>–<xref rid="R3" ref-type="bibr">3</xref></sup> and influenza virus<sup><xref rid="R4" ref-type="bibr">4</xref>–<xref rid="R8" ref-type="bibr">8</xref></sup>, and the design of immunogens to elicit them is a goal of vaccine research in both fields. Residues in the RBS of influenza virus hemagglutinin (HA) determine a preference for the avian or human receptor, α -2,3-linked sialic acid and α -2,6-linked sialic acid, respectively<sup><xref rid="R9" ref-type="bibr">9</xref>,<xref rid="R10" ref-type="bibr">10</xref></sup>. Transmission of an avian-origin virus between humans generally requires one or more mutations in the sequences encoding the influenza virus RBS to change the preferred receptor from avian to human<sup><xref rid="R9" ref-type="bibr">9</xref>,<xref rid="R11" ref-type="bibr">11</xref>,<xref rid="R12" ref-type="bibr">12</xref></sup>, but passage of a human-derived vaccine candidate in chicken eggs can select for reversion to avian receptor preference<sup><xref rid="R13" ref-type="bibr">13</xref>–<xref rid="R15" ref-type="bibr">15</xref></sup>. For example, the X-181 strain of the 2009 new pandemic H1N1 influenza virus, derived from the A/California/07/2009 isolate and used in essentially all vaccines since 2009, has arginine at position 226, a residue known to confer preference for an α -2,3 linkage in H1 subtype viruses<sup><xref rid="R13" ref-type="bibr">13</xref>,<xref rid="R14" ref-type="bibr">14</xref></sup>; the wild-type A/California/07/2009 isolate, like most circulating human H1N1 viruses, has glutamine at position 226. We describe, from three different individuals, RBS-directed antibodies that recognize the avian-adapted H1 strain in current influenza vaccines but not the circulating new pandemic 2009 virus; Arg226 in the vaccine-strain RBS accounts for the restriction. The polyclonal sera of the three donors also reflect this preference. Therefore, when vaccines produced from strains that are never passaged in avian cells become widely available, they may prove more capable of eliciting RBS-directed, broadly neutralizing antibodies than those produced from egg-adapted viruses, extending the established benefits of current seasonal influenza immunizations.</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>
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<front><journal-meta><journal-id journal-id-type="nlm-journal-id">9502015</journal-id><journal-id journal-id-type="pubmed-jr-id">8791</journal-id><journal-id journal-id-type="nlm-ta">Nat Med</journal-id><journal-id journal-id-type="iso-abbrev">Nat. Med.</journal-id><journal-title-group><journal-title>Nature medicine</journal-title></journal-title-group><issn pub-type="ppub">1078-8956</issn><issn pub-type="epub">1546-170X</issn></journal-meta><article-meta><article-id pub-id-type="pmid">27820604</article-id><article-id pub-id-type="pmc">5485662</article-id><article-id pub-id-type="doi">10.1038/nm.4223</article-id><article-id pub-id-type="manuscript">NIHMS867171</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Influenza immunization elicits antibodies specific for an egg-adapted vaccine strain</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Raymond</surname><given-names>Donald D</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Stewart</surname><given-names>Shaun M</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref rid="FN2" ref-type="author-notes">14</xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Jiwon</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Ferdman</surname><given-names>Jack</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Bajic</surname><given-names>Goran</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Do</surname><given-names>Khoi T</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ernandes</surname><given-names>Michael J</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Suphaphiphat</surname><given-names>Pirada</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Settembre</surname><given-names>Ethan C</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Dormitzer</surname><given-names>Philip R</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref rid="FN2" ref-type="author-notes">14</xref></contrib><contrib contrib-type="author"><name><surname>Giudice</surname><given-names>Giuseppe Del</given-names></name><xref ref-type="aff" rid="A5">5</xref><xref rid="FN2" ref-type="author-notes">14</xref></contrib><contrib contrib-type="author"><name><surname>Finco</surname><given-names>Oretta</given-names></name><xref ref-type="aff" rid="A5">5</xref><xref rid="FN2" ref-type="author-notes">14</xref></contrib><contrib contrib-type="author"><name><surname>Kang</surname><given-names>Tae Hyun</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Ippolito</surname><given-names>Gregory C</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Georgiou</surname><given-names>George</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Kepler</surname><given-names>Thomas B</given-names></name><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Haynes</surname><given-names>Barton F</given-names></name><xref ref-type="aff" rid="A10">10</xref><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Moody</surname><given-names>M Anthony</given-names></name><xref ref-type="aff" rid="A10">10</xref><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Liao</surname><given-names>Hua-Xin</given-names></name><xref ref-type="aff" rid="A10">10</xref><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Schmidt</surname><given-names>Aaron G</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Harrison</surname><given-names>Stephen C</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A13">13</xref></contrib></contrib-group><aff id="A1"><label>1</label>Laboratory of Molecular Medicine, Boston Children’s Hospital, Harvard Medical School</aff><aff id="A2"><label>2</label>Seqirus, 45 Sidney St., Cambridge, Massachusetts, USA</aff><aff id="A3"><label>3</label>Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA</aff><aff id="A4"><label>4</label>Graduate Program in Virology, Harvard Medical School, Boston, Massachusetts, USA</aff><aff id="A5"><label>5</label>Novartis Vaccines and Diagnostics, Siena, Italy</aff><aff id="A6"><label>6</label>Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA</aff><aff id="A7"><label>7</label>Center of Systems and Synthetic Biology, University of Texas at Austin, Austin, Texas, USA</aff><aff id="A8"><label>8</label>Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, USA</aff><aff id="A9"><label>9</label>Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA</aff><aff id="A10"><label>10</label>Duke Human Vaccine Institute, Duke University Medical School, Durham, North Carolina, USA</aff><aff id="A11"><label>11</label>Department of Medicine, Duke University Medical School, Durham, North Carolina, USA</aff><aff id="A12"><label>12</label>Department of Pediatrics, Duke University Medical School, Durham, North Carolina, USA</aff><aff id="A13"><label>13</label>Howard Hughes Medical Institute, Boston, Massachusetts, USA</aff><author-notes><corresp id="FN1">Correspondence should be addressed to S.C.H. (<email>harrison@crystal.harvard.edu</email>)</corresp><fn id="FN2" fn-type="present-address"><label>14</label><p>Present addresses: Incyte, Wilmington, Delaware, USA (S.M.S.); Pfizer Vaccines Research and Development, Pearl River, New York, USA (P.R.D.); GSK Vaccines, Siena, Italy (G.D.G. and O.F.).</p></fn><fn fn-type="COI-statement" id="FN6"><p><bold>COMPETING FINANCIAL INTERESTS</bold></p><p>The authors declare competing financial interests: details are available in the online version of the paper.</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>24</day><month>4</month><year>2017</year></pub-date><pub-date pub-type="epub"><day>07</day><month>11</month><year>2016</year></pub-date><pub-date pub-type="ppub"><month>12</month><year>2016</year></pub-date><pub-date pub-type="pmc-release"><day>27</day><month>6</month><year>2017</year></pub-date><volume>22</volume><issue>12</issue><fpage>1465</fpage><lpage>1469</lpage><pmc-comment>elocation-id from pubmed: 10.1038/nm.4223</pmc-comment>
<permissions><license license-type="permissions-link"><license-p>Reprints and permissions information is available online at <ext-link ext-link-type="uri" xlink:href="http://www.nature.com/reprints/index.html">http://www.nature.com/reprints/index.html</ext-link>.</license-p></license></permissions><abstract><p id="P1">For broad protection against infection by viruses such as influenza or HIV, vaccines should elicit antibodies that bind conserved viral epitopes, such as the receptor-binding site (RBS). RBS-directed antibodies have been described for both HIV<sup><xref rid="R1" ref-type="bibr">1</xref>–<xref rid="R3" ref-type="bibr">3</xref></sup> and influenza virus<sup><xref rid="R4" ref-type="bibr">4</xref>–<xref rid="R8" ref-type="bibr">8</xref></sup>, and the design of immunogens to elicit them is a goal of vaccine research in both fields. Residues in the RBS of influenza virus hemagglutinin (HA) determine a preference for the avian or human receptor, α -2,3-linked sialic acid and α -2,6-linked sialic acid, respectively<sup><xref rid="R9" ref-type="bibr">9</xref>,<xref rid="R10" ref-type="bibr">10</xref></sup>. Transmission of an avian-origin virus between humans generally requires one or more mutations in the sequences encoding the influenza virus RBS to change the preferred receptor from avian to human<sup><xref rid="R9" ref-type="bibr">9</xref>,<xref rid="R11" ref-type="bibr">11</xref>,<xref rid="R12" ref-type="bibr">12</xref></sup>, but passage of a human-derived vaccine candidate in chicken eggs can select for reversion to avian receptor preference<sup><xref rid="R13" ref-type="bibr">13</xref>–<xref rid="R15" ref-type="bibr">15</xref></sup>. For example, the X-181 strain of the 2009 new pandemic H1N1 influenza virus, derived from the A/California/07/2009 isolate and used in essentially all vaccines since 2009, has arginine at position 226, a residue known to confer preference for an α -2,3 linkage in H1 subtype viruses<sup><xref rid="R13" ref-type="bibr">13</xref>,<xref rid="R14" ref-type="bibr">14</xref></sup>; the wild-type A/California/07/2009 isolate, like most circulating human H1N1 viruses, has glutamine at position 226. We describe, from three different individuals, RBS-directed antibodies that recognize the avian-adapted H1 strain in current influenza vaccines but not the circulating new pandemic 2009 virus; Arg226 in the vaccine-strain RBS accounts for the restriction. The polyclonal sera of the three donors also reflect this preference. Therefore, when vaccines produced from strains that are never passaged in avian cells become widely available, they may prove more capable of eliciting RBS-directed, broadly neutralizing antibodies than those produced from egg-adapted viruses, extending the established benefits of current seasonal influenza immunizations.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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