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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">H7N9 influenza virus neutralizing antibodies that possess few somatic mutations</title><author><name sortKey="Thornburg, Natalie J" sort="Thornburg, Natalie J" uniqKey="Thornburg N" first="Natalie J." last="Thornburg">Natalie J. Thornburg</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff></affiliation></author><author><name sortKey="Zhang, Heng" sort="Zhang, Heng" uniqKey="Zhang H" first="Heng" last="Zhang">Heng Zhang</name><affiliation><nlm:aff id="A3">Department of Integrative Structural and Computational Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA.</nlm:aff></affiliation></author><author><name sortKey="Bangaru, Sandhya" sort="Bangaru, Sandhya" uniqKey="Bangaru S" first="Sandhya" last="Bangaru">Sandhya Bangaru</name><affiliation><nlm:aff wicri:cut=", and" id="A4">Departments of Pathology, Microbiology, and Immunology</nlm:aff></affiliation></author><author><name sortKey="Sapparapu, Gopal" sort="Sapparapu, Gopal" uniqKey="Sapparapu G" first="Gopal" last="Sapparapu">Gopal Sapparapu</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff></affiliation></author><author><name sortKey="Kose, Nurgun" sort="Kose, Nurgun" uniqKey="Kose N" first="Nurgun" last="Kose">Nurgun Kose</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation></author><author><name sortKey="Lampley, Rebecca M" sort="Lampley, Rebecca M" uniqKey="Lampley R" first="Rebecca M." last="Lampley">Rebecca M. Lampley</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation></author><author><name sortKey="Bombardi, Robin G" sort="Bombardi, Robin G" uniqKey="Bombardi R" first="Robin G." last="Bombardi">Robin G. Bombardi</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation></author><author><name sortKey="Yu, Yingchun" sort="Yu, Yingchun" uniqKey="Yu Y" first="Yingchun" last="Yu">Yingchun Yu</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation></author><author><name sortKey="Graham, Stephen" sort="Graham, Stephen" uniqKey="Graham S" first="Stephen" last="Graham">Stephen Graham</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation></author><author><name sortKey="Branchizio, Andre" sort="Branchizio, Andre" uniqKey="Branchizio A" first="Andre" last="Branchizio">Andre Branchizio</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation></author><author><name sortKey="Yoder, Sandra M" sort="Yoder, Sandra M" uniqKey="Yoder S" first="Sandra M." last="Yoder">Sandra M. Yoder</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Vanderbilt Vaccine Research Program, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff></affiliation></author><author><name sortKey="Rock, Michael T" sort="Rock, Michael T" uniqKey="Rock M" first="Michael T." last="Rock">Michael T. Rock</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Vanderbilt Vaccine Research Program, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff></affiliation></author><author><name sortKey="Creech, C Buddy" sort="Creech, C Buddy" uniqKey="Creech C" first="C. Buddy" last="Creech">C. Buddy Creech</name><affiliation><nlm:aff id="A2">Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Vanderbilt Vaccine Research Program, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff></affiliation></author><author><name sortKey="Edwards, Kathryn M" sort="Edwards, Kathryn M" uniqKey="Edwards K" first="Kathryn M." last="Edwards">Kathryn M. Edwards</name><affiliation><nlm:aff id="A2">Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Vanderbilt Vaccine Research Program, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff></affiliation></author><author><name sortKey="Lee, David" sort="Lee, David" uniqKey="Lee D" first="David" last="Lee">David Lee</name><affiliation><nlm:aff id="A6">Department of Medicine and Biomedical Sciences Graduate Program, School of Medicine, UCSD, San Diego, California, USA.</nlm:aff></affiliation></author><author><name sortKey="Li, Sheng" sort="Li, Sheng" uniqKey="Li S" first="Sheng" last="Li">Sheng Li</name><affiliation><nlm:aff id="A6">Department of Medicine and Biomedical Sciences Graduate Program, School of Medicine, UCSD, San Diego, California, USA.</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="A3">Department of Integrative Structural and Computational Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA.</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="A7">Department of Microbiology,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="A8">Global Health and Emerging Pathogens Institute</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Department of Medicine, Division of Infectious Diseases at Icahn School of Medicine at Mount Sinai (ISMMS), New York, New York, USA.</nlm:aff></affiliation></author><author><name sortKey="Albrecht, Randy A" sort="Albrecht, Randy A" uniqKey="Albrecht R" first="Randy A." last="Albrecht">Randy A. Albrecht</name><affiliation><nlm:aff id="A7">Department of Microbiology,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="A8">Global Health and Emerging Pathogens Institute</nlm:aff></affiliation></author><author><name sortKey="Crowe, James E" sort="Crowe, James E" uniqKey="Crowe J" first="James E." last="Crowe">James E. Crowe</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="A4">Departments of Pathology, Microbiology, and Immunology</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26950424</idno><idno type="pmc">4811156</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4811156</idno><idno type="RBID">PMC:4811156</idno><idno type="doi">10.1172/JCI85317</idno><date when="????">????</date><idno type="wicri:Area/Pmc/Corpus">000052</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000052</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">H7N9 influenza virus neutralizing antibodies that possess few somatic mutations</title><author><name sortKey="Thornburg, Natalie J" sort="Thornburg, Natalie J" uniqKey="Thornburg N" first="Natalie J." last="Thornburg">Natalie J. Thornburg</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff></affiliation></author><author><name sortKey="Zhang, Heng" sort="Zhang, Heng" uniqKey="Zhang H" first="Heng" last="Zhang">Heng Zhang</name><affiliation><nlm:aff id="A3">Department of Integrative Structural and Computational Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA.</nlm:aff></affiliation></author><author><name sortKey="Bangaru, Sandhya" sort="Bangaru, Sandhya" uniqKey="Bangaru S" first="Sandhya" last="Bangaru">Sandhya Bangaru</name><affiliation><nlm:aff wicri:cut=", and" id="A4">Departments of Pathology, Microbiology, and Immunology</nlm:aff></affiliation></author><author><name sortKey="Sapparapu, Gopal" sort="Sapparapu, Gopal" uniqKey="Sapparapu G" first="Gopal" last="Sapparapu">Gopal Sapparapu</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff></affiliation></author><author><name sortKey="Kose, Nurgun" sort="Kose, Nurgun" uniqKey="Kose N" first="Nurgun" last="Kose">Nurgun Kose</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation></author><author><name sortKey="Lampley, Rebecca M" sort="Lampley, Rebecca M" uniqKey="Lampley R" first="Rebecca M." last="Lampley">Rebecca M. Lampley</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation></author><author><name sortKey="Bombardi, Robin G" sort="Bombardi, Robin G" uniqKey="Bombardi R" first="Robin G." last="Bombardi">Robin G. Bombardi</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation></author><author><name sortKey="Yu, Yingchun" sort="Yu, Yingchun" uniqKey="Yu Y" first="Yingchun" last="Yu">Yingchun Yu</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation></author><author><name sortKey="Graham, Stephen" sort="Graham, Stephen" uniqKey="Graham S" first="Stephen" last="Graham">Stephen Graham</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation></author><author><name sortKey="Branchizio, Andre" sort="Branchizio, Andre" uniqKey="Branchizio A" first="Andre" last="Branchizio">Andre Branchizio</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation></author><author><name sortKey="Yoder, Sandra M" sort="Yoder, Sandra M" uniqKey="Yoder S" first="Sandra M." last="Yoder">Sandra M. Yoder</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Vanderbilt Vaccine Research Program, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff></affiliation></author><author><name sortKey="Rock, Michael T" sort="Rock, Michael T" uniqKey="Rock M" first="Michael T." last="Rock">Michael T. Rock</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Vanderbilt Vaccine Research Program, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff></affiliation></author><author><name sortKey="Creech, C Buddy" sort="Creech, C Buddy" uniqKey="Creech C" first="C. Buddy" last="Creech">C. Buddy Creech</name><affiliation><nlm:aff id="A2">Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Vanderbilt Vaccine Research Program, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff></affiliation></author><author><name sortKey="Edwards, Kathryn M" sort="Edwards, Kathryn M" uniqKey="Edwards K" first="Kathryn M." last="Edwards">Kathryn M. Edwards</name><affiliation><nlm:aff id="A2">Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Vanderbilt Vaccine Research Program, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff></affiliation></author><author><name sortKey="Lee, David" sort="Lee, David" uniqKey="Lee D" first="David" last="Lee">David Lee</name><affiliation><nlm:aff id="A6">Department of Medicine and Biomedical Sciences Graduate Program, School of Medicine, UCSD, San Diego, California, USA.</nlm:aff></affiliation></author><author><name sortKey="Li, Sheng" sort="Li, Sheng" uniqKey="Li S" first="Sheng" last="Li">Sheng Li</name><affiliation><nlm:aff id="A6">Department of Medicine and Biomedical Sciences Graduate Program, School of Medicine, UCSD, San Diego, California, USA.</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="A3">Department of Integrative Structural and Computational Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA.</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="A7">Department of Microbiology,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="A8">Global Health and Emerging Pathogens Institute</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Department of Medicine, Division of Infectious Diseases at Icahn School of Medicine at Mount Sinai (ISMMS), New York, New York, USA.</nlm:aff></affiliation></author><author><name sortKey="Albrecht, Randy A" sort="Albrecht, Randy A" uniqKey="Albrecht R" first="Randy A." last="Albrecht">Randy A. Albrecht</name><affiliation><nlm:aff id="A7">Department of Microbiology,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="A8">Global Health and Emerging Pathogens Institute</nlm:aff></affiliation></author><author><name sortKey="Crowe, James E" sort="Crowe, James E" uniqKey="Crowe J" first="James E." last="Crowe">James E. Crowe</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="A4">Departments of Pathology, Microbiology, and Immunology</nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Clinical Investigation</title><idno type="ISSN">0021-9738</idno><idno type="eISSN">1558-8238</idno><imprint><date when="????">????</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Avian H7N9 influenza viruses are group 2 influenza A viruses that have been identified as the etiologic agent for a current major outbreak that began in China in 2013 and may pose a pandemic threat. Here, we examined the human H7-reactive antibody response in 75 recipients of a monovalent inactivated A/Shanghai/02/2013 H7N9 vaccine. After 2 doses of vaccine, the majority of donors had memory B cells that secreted IgGs specific for H7 HA, with dominant responses against single HA subtypes, although frequencies of H7-reactive B cells ranged widely between donors. We isolated 12 naturally occurring mAbs with low half-maximal effective concentrations for binding, 5 of which possessed neutralizing and HA-inhibiting activities. The 5 neutralizing mAbs exhibited narrow breadth of reactivity with influenza H7 strains. Epitope-mapping studies using neutralization escape mutant analysis, deuterium exchange mass spectrometry, and x-ray crystallography revealed that these neutralizing mAbs bind near the receptor-binding pocket on HA. All 5 neutralizing mAbs possessed low numbers of somatic mutations, suggesting the clones arose from naive B cells. The most potent mAb, H7.167, was tested as a prophylactic treatment in a mouse intranasal virus challenge study, and systemic administration of the mAb markedly reduced viral lung titers.</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>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Clin Invest</journal-id><journal-id journal-id-type="iso-abbrev">J. Clin. Invest</journal-id><journal-id journal-id-type="publisher-id">J Clin Invest</journal-id><journal-title-group><journal-title>The Journal of Clinical Investigation</journal-title></journal-title-group><issn pub-type="ppub">0021-9738</issn><issn pub-type="epub">1558-8238</issn><publisher><publisher-name>American Society for Clinical Investigation</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26950424</article-id><article-id pub-id-type="pmc">4811156</article-id><article-id pub-id-type="publisher-id">85317</article-id><article-id pub-id-type="doi">10.1172/JCI85317</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>H7N9 influenza virus neutralizing antibodies that possess few somatic mutations</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Thornburg</surname><given-names>Natalie J.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Heng</given-names></name><email>zhangh@scripps.edu</email><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Bangaru</surname><given-names>Sandhya</given-names></name><email>sandhya.bangaru@Vanderbilt.Edu</email><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0001-9670-1757</contrib-id><name><surname>Sapparapu</surname><given-names>Gopal</given-names></name><email>gopal.sapparapu@Vanderbilt.Edu</email><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kose</surname><given-names>Nurgun</given-names></name><email>nurgun.kose@Vanderbilt.Edu</email><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Lampley</surname><given-names>Rebecca M.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Bombardi</surname><given-names>Robin G.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Yu</surname><given-names>Yingchun</given-names></name><email>yuantou8@gmail.com</email><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Graham</surname><given-names>Stephen</given-names></name><email>sdgraham118@gmail.com</email><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Branchizio</surname><given-names>Andre</given-names></name><email>andre.j.branchizio@Vanderbilt.Edu</email><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Yoder</surname><given-names>Sandra M.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Rock</surname><given-names>Michael T.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Creech</surname><given-names>C. Buddy</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Edwards</surname><given-names>Kathryn M.</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>David</given-names></name><email>David.Lee@med.wmich.edu</email><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Sheng</given-names></name><email>s4li@ucsd.edu</email><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Wilson</surname><given-names>Ian A.</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>García-Sastre</surname><given-names>Adolfo</given-names></name><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Albrecht</surname><given-names>Randy A.</given-names></name><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Crowe</surname><given-names>James E.</given-names><suffix>Jr.</suffix></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A4">4</xref></contrib></contrib-group><aff id="A1"><label>1</label>The Vanderbilt Vaccine Center and</aff><aff id="A2"><label>2</label>Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</aff><aff id="A3"><label>3</label>Department of Integrative Structural and Computational Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA.</aff><aff id="A4"><label>4</label>Departments of Pathology, Microbiology, and Immunology, and</aff><aff id="A5"><label>5</label>Vanderbilt Vaccine Research Program, Vanderbilt University, Nashville, Tennessee, USA.</aff><aff id="A6"><label>6</label>Department of Medicine and Biomedical Sciences Graduate Program, School of Medicine, UCSD, San Diego, California, USA.</aff><aff id="A7"><label>7</label>Department of Microbiology,</aff><aff id="A8"><label>8</label>Global Health and Emerging Pathogens Institute, and</aff><aff id="A9"><label>9</label>Department of Medicine, Division of Infectious Diseases at Icahn School of Medicine at Mount Sinai (ISMMS), New York, New York, USA.</aff><author-notes><corresp>Address correspondence to: James E. Crowe Jr., Vanderbilt Vaccine Center, Vanderbilt University Medical Center, 11475 MRB IV, 2213 Garland Avenue, Nashville, Tennessee 37232-0417, USA. Phone: 615.343.8064; E-mail: <email>james.crowe@vanderbilt.edu</email>.</corresp></author-notes><pub-date date-type="pub" publication-format="electronic" iso-8601-date="2016-03-07"><day>7</day><month>3</month><year>2016</year></pub-date><pub-date date-type="pub" publication-format="print" iso-8601-date="2016-04-01"><day>1</day><month>4</month><year>2016</year></pub-date><pub-date pub-type="pmc-release"><day>1</day><month>7</month><year>2016</year></pub-date><pmc-comment> PMC Release delay is 3 months and
0 days and was based on the
<volume>126</volume><issue>4</issue><fpage>1482</fpage><lpage>1494</lpage><history><date date-type="received"><day>30</day><month>10</month><year>2015</year></date><date date-type="accepted"><day>21</day><month>1</month><year>2016</year></date></history><permissions><copyright-statement>Copyright © 2016, American Society for Clinical Investigation</copyright-statement><copyright-year>2016</copyright-year><copyright-holder>American Society for Clinical Investigation</copyright-holder></permissions><self-uri xlink:href="https://www.jci.org/articles/view/85317">This article is available online at https://www.jci.org/articles/view/85317</self-uri><abstract><p>Avian H7N9 influenza viruses are group 2 influenza A viruses that have been identified as the etiologic agent for a current major outbreak that began in China in 2013 and may pose a pandemic threat. Here, we examined the human H7-reactive antibody response in 75 recipients of a monovalent inactivated A/Shanghai/02/2013 H7N9 vaccine. After 2 doses of vaccine, the majority of donors had memory B cells that secreted IgGs specific for H7 HA, with dominant responses against single HA subtypes, although frequencies of H7-reactive B cells ranged widely between donors. We isolated 12 naturally occurring mAbs with low half-maximal effective concentrations for binding, 5 of which possessed neutralizing and HA-inhibiting activities. The 5 neutralizing mAbs exhibited narrow breadth of reactivity with influenza H7 strains. Epitope-mapping studies using neutralization escape mutant analysis, deuterium exchange mass spectrometry, and x-ray crystallography revealed that these neutralizing mAbs bind near the receptor-binding pocket on HA. All 5 neutralizing mAbs possessed low numbers of somatic mutations, suggesting the clones arose from naive B cells. The most potent mAb, H7.167, was tested as a prophylactic treatment in a mouse intranasal virus challenge study, and systemic administration of the mAb markedly reduced viral lung titers.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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