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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">H5N1 vaccine-elicited memory B cells are genetically constrained by the IGHV locus in the recognition of a neutralizing epitope in the HA stem</title><author><name sortKey="Wheatley, Adam K" sort="Wheatley, Adam K" uniqKey="Wheatley A" first="Adam K" last="Wheatley">Adam K. Wheatley</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Whittle, James Rr" sort="Whittle, James Rr" uniqKey="Whittle J" first="James Rr" last="Whittle">James Rr Whittle</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Lingwood, Daniel" sort="Lingwood, Daniel" uniqKey="Lingwood D" first="Daniel" last="Lingwood">Daniel Lingwood</name><affiliation><nlm:aff id="A3"> Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America</nlm:aff></affiliation></author><author><name sortKey="Kanekiyo, Masaru" sort="Kanekiyo, Masaru" uniqKey="Kanekiyo M" first="Masaru" last="Kanekiyo">Masaru Kanekiyo</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Yassine, Hadi M" sort="Yassine, Hadi M" uniqKey="Yassine H" first="Hadi M" last="Yassine">Hadi M. Yassine</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Ma, Steven S" sort="Ma, Steven S" uniqKey="Ma S" first="Steven S" last="Ma">Steven S. Ma</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Narpala, Sandeep R" sort="Narpala, Sandeep R" uniqKey="Narpala S" first="Sandeep R" last="Narpala">Sandeep R. Narpala</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Prabhakaran, Madhu S" sort="Prabhakaran, Madhu S" uniqKey="Prabhakaran M" first="Madhu S" last="Prabhakaran">Madhu S. Prabhakaran</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Matus Nicodemos, Rodrigo A" sort="Matus Nicodemos, Rodrigo A" uniqKey="Matus Nicodemos R" first="Rodrigo A" last="Matus-Nicodemos">Rodrigo A. Matus-Nicodemos</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Bailer, Robert T" sort="Bailer, Robert T" uniqKey="Bailer R" first="Robert T" last="Bailer">Robert T. Bailer</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Nabel, Gary J" sort="Nabel, Gary J" uniqKey="Nabel G" first="Gary J" last="Nabel">Gary J. Nabel</name><affiliation><nlm:aff id="A2"> Sanofi, Cambridge, Massachusetts, United States of America</nlm:aff></affiliation></author><author><name sortKey="Graham, Barney S" sort="Graham, Barney S" uniqKey="Graham B" first="Barney S" last="Graham">Barney S. Graham</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Ledgerwood, Julie E" sort="Ledgerwood, Julie E" uniqKey="Ledgerwood J" first="Julie E" last="Ledgerwood">Julie E. Ledgerwood</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Koup, Richard A" sort="Koup, Richard A" uniqKey="Koup R" first="Richard A" last="Koup">Richard A. Koup</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Mcdermott, Adrian B" sort="Mcdermott, Adrian B" uniqKey="Mcdermott A" first="Adrian B" last="Mcdermott">Adrian B. Mcdermott</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26078272</idno><idno type="pmc">4491024</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491024</idno><idno type="RBID">PMC:4491024</idno><idno type="doi">10.4049/jimmunol.1402835</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000843</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000843</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">H5N1 vaccine-elicited memory B cells are genetically constrained by the IGHV locus in the recognition of a neutralizing epitope in the HA stem</title><author><name sortKey="Wheatley, Adam K" sort="Wheatley, Adam K" uniqKey="Wheatley A" first="Adam K" last="Wheatley">Adam K. Wheatley</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Whittle, James Rr" sort="Whittle, James Rr" uniqKey="Whittle J" first="James Rr" last="Whittle">James Rr Whittle</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Lingwood, Daniel" sort="Lingwood, Daniel" uniqKey="Lingwood D" first="Daniel" last="Lingwood">Daniel Lingwood</name><affiliation><nlm:aff id="A3"> Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America</nlm:aff></affiliation></author><author><name sortKey="Kanekiyo, Masaru" sort="Kanekiyo, Masaru" uniqKey="Kanekiyo M" first="Masaru" last="Kanekiyo">Masaru Kanekiyo</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Yassine, Hadi M" sort="Yassine, Hadi M" uniqKey="Yassine H" first="Hadi M" last="Yassine">Hadi M. Yassine</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Ma, Steven S" sort="Ma, Steven S" uniqKey="Ma S" first="Steven S" last="Ma">Steven S. Ma</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Narpala, Sandeep R" sort="Narpala, Sandeep R" uniqKey="Narpala S" first="Sandeep R" last="Narpala">Sandeep R. Narpala</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Prabhakaran, Madhu S" sort="Prabhakaran, Madhu S" uniqKey="Prabhakaran M" first="Madhu S" last="Prabhakaran">Madhu S. Prabhakaran</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Matus Nicodemos, Rodrigo A" sort="Matus Nicodemos, Rodrigo A" uniqKey="Matus Nicodemos R" first="Rodrigo A" last="Matus-Nicodemos">Rodrigo A. Matus-Nicodemos</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Bailer, Robert T" sort="Bailer, Robert T" uniqKey="Bailer R" first="Robert T" last="Bailer">Robert T. Bailer</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Nabel, Gary J" sort="Nabel, Gary J" uniqKey="Nabel G" first="Gary J" last="Nabel">Gary J. Nabel</name><affiliation><nlm:aff id="A2"> Sanofi, Cambridge, Massachusetts, United States of America</nlm:aff></affiliation></author><author><name sortKey="Graham, Barney S" sort="Graham, Barney S" uniqKey="Graham B" first="Barney S" last="Graham">Barney S. Graham</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Ledgerwood, Julie E" sort="Ledgerwood, Julie E" uniqKey="Ledgerwood J" first="Julie E" last="Ledgerwood">Julie E. Ledgerwood</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Koup, Richard A" sort="Koup, Richard A" uniqKey="Koup R" first="Richard A" last="Koup">Richard A. Koup</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author><author><name sortKey="Mcdermott, Adrian B" sort="Mcdermott, Adrian B" uniqKey="Mcdermott A" first="Adrian B" last="Mcdermott">Adrian B. Mcdermott</name><affiliation><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff></affiliation></author></analytic><series><title level="j">Journal of immunology (Baltimore, Md. : 1950)</title><idno type="ISSN">0022-1767</idno><idno type="eISSN">1550-6606</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Due to significant viral diversity, vaccines that elicit durable and broad protection against influenza have been elusive. Recent research has focused on the potential of highly conserved regions of the viral hemagglutinin (HA) as targets for broadly neutralizing antibody responses. Antibodies that bind the highly conserved stem or stalk of HA can be elicited by vaccination in humans and animal models and neutralize diverse influenza strains. However, the frequency and phenotype of HA stem-specific B cells in vivo remains unclear. Here we characterize HA stem-specific B cell responses following H5N1 vaccination and describe the re-expansion of a pre-existing population of memory B cells specific for stem epitopes. This population utilizes primarily, but not exclusively, IGHV1-69-based immunoglobulins for HA recognition. However within some subjects, allelic polymorphism at the <italic>ighv1-69</italic> locus can limit IGHV1-69 immunodominance and may reduce circulating frequencies of stem-reactive B cells in vivo. The accurate definition of allelic selection, recombination requirements and ontogeny of neutralizing antibody responses to influenza will aid rational influenza vaccine design.</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">2985117R</journal-id><journal-id journal-id-type="pubmed-jr-id">4816</journal-id><journal-id journal-id-type="nlm-ta">J Immunol</journal-id><journal-id journal-id-type="iso-abbrev">J. Immunol.</journal-id><journal-title-group><journal-title>Journal of immunology (Baltimore, Md. : 1950)</journal-title></journal-title-group><issn pub-type="ppub">0022-1767</issn><issn pub-type="epub">1550-6606</issn></journal-meta><article-meta><article-id pub-id-type="pmid">26078272</article-id><article-id pub-id-type="pmc">4491024</article-id><article-id pub-id-type="doi">10.4049/jimmunol.1402835</article-id><article-id pub-id-type="manuscript">NIHMS692205</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>H5N1 vaccine-elicited memory B cells are genetically constrained by the IGHV locus in the recognition of a neutralizing epitope in the HA stem</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Wheatley</surname><given-names>Adam K</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Whittle</surname><given-names>James RR</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Lingwood</surname><given-names>Daniel</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Kanekiyo</surname><given-names>Masaru</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Yassine</surname><given-names>Hadi M</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ma</surname><given-names>Steven S</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Narpala</surname><given-names>Sandeep R</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Prabhakaran</surname><given-names>Madhu S</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Matus-Nicodemos</surname><given-names>Rodrigo A</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Bailer</surname><given-names>Robert T</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Nabel</surname><given-names>Gary J</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Graham</surname><given-names>Barney S</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ledgerwood</surname><given-names>Julie E</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Koup</surname><given-names>Richard A</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>McDermott</surname><given-names>Adrian B</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="corresp" rid="CR1">*</xref></contrib></contrib-group><aff id="A1"><label>1</label> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</aff><aff id="A2"><label>2</label> Sanofi, Cambridge, Massachusetts, United States of America</aff><aff id="A3"><label>3</label> Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America</aff><author-notes><corresp id="CR1"><label>*</label> Corresponding Author A B McDermott, 40 Covent Drive, Rm3508, Bethesda, MD 20892, <email>adrian.mcdermott@nih.gov</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>20</day><month>5</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>15</day><month>6</month><year>2015</year></pub-date><pub-date pub-type="ppub"><day>15</day><month>7</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>15</day><month>7</month><year>2016</year></pub-date><volume>195</volume><issue>2</issue><fpage>602</fpage><lpage>610</lpage><pmc-comment>elocation-id from pubmed: 10.4049/jimmunol.1402835</pmc-comment>
<abstract><p id="P1">Due to significant viral diversity, vaccines that elicit durable and broad protection against influenza have been elusive. Recent research has focused on the potential of highly conserved regions of the viral hemagglutinin (HA) as targets for broadly neutralizing antibody responses. Antibodies that bind the highly conserved stem or stalk of HA can be elicited by vaccination in humans and animal models and neutralize diverse influenza strains. However, the frequency and phenotype of HA stem-specific B cells in vivo remains unclear. Here we characterize HA stem-specific B cell responses following H5N1 vaccination and describe the re-expansion of a pre-existing population of memory B cells specific for stem epitopes. This population utilizes primarily, but not exclusively, IGHV1-69-based immunoglobulins for HA recognition. However within some subjects, allelic polymorphism at the <italic>ighv1-69</italic> locus can limit IGHV1-69 immunodominance and may reduce circulating frequencies of stem-reactive B cells in vivo. The accurate definition of allelic selection, recombination requirements and ontogeny of neutralizing antibody responses to influenza will aid rational influenza vaccine design.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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