H7N9 influenza virus neutralizing antibodies that possess few somatic mutations
Identifieur interne : 002E54 ( Main/Exploration ); précédent : 002E53; suivant : 002E55H7N9 influenza virus neutralizing antibodies that possess few somatic mutations
Auteurs : Natalie J. Thornburg [États-Unis] ; Heng Zhang [États-Unis] ; Sandhya Bangaru ; Gopal Sapparapu [États-Unis] ; Nurgun Kose ; Rebecca M. Lampley ; Robin G. Bombardi ; Yingchun Yu ; Stephen Graham ; Andre Branchizio ; Sandra M. Yoder [États-Unis] ; Michael T. Rock [États-Unis] ; C. Buddy Creech [États-Unis] ; Kathryn M. Edwards [États-Unis] ; David Lee [États-Unis] ; Sheng Li [États-Unis] ; Ian A. Wilson [États-Unis] ; Adolfo García-Sastre [États-Unis] ; Randy A. Albrecht ; James E. Crowe [États-Unis]Source :
- The Journal of Clinical Investigation [ 0021-9738 ] ; ????.
Abstract
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.
Url:
DOI: 10.1172/JCI85317
PubMed: 26950424
PubMed Central: 4811156
Affiliations:
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Thornburg</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Pediatrics, Vanderbilt University, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation></author><author><name sortKey="Zhang, Heng" sort="Zhang, Heng" uniqKey="Zhang H" first="Heng" last="Zhang">Heng Zhang</name><affiliation wicri:level="2"><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><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Integrative Structural and Computational Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></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><wicri:noCountry code="subfield">and Immunology</wicri:noCountry></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 wicri:level="2"><nlm:aff id="A2">Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Pediatrics, Vanderbilt University, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></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. 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Thornburg</name><affiliation><nlm:aff wicri:cut=" and" id="A1">The Vanderbilt Vaccine Center</nlm:aff></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Pediatrics, Vanderbilt University, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation></author><author><name sortKey="Zhang, Heng" sort="Zhang, Heng" uniqKey="Zhang H" first="Heng" last="Zhang">Heng Zhang</name><affiliation wicri:level="2"><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><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Integrative Structural and Computational Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></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><wicri:noCountry code="subfield">and Immunology</wicri:noCountry></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 wicri:level="2"><nlm:aff id="A2">Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Pediatrics, Vanderbilt University, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></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 wicri:level="2"><nlm:aff id="A5">Vanderbilt Vaccine Research Program, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Vanderbilt Vaccine Research Program, Vanderbilt University, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></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 wicri:level="2"><nlm:aff id="A2">Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Pediatrics, Vanderbilt University, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A5">Vanderbilt Vaccine Research Program, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Vanderbilt Vaccine Research Program, Vanderbilt University, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></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 wicri:level="2"><nlm:aff id="A2">Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Pediatrics, Vanderbilt University, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A5">Vanderbilt Vaccine Research Program, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Vanderbilt Vaccine Research Program, Vanderbilt University, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></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 wicri:level="2"><nlm:aff id="A2">Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Pediatrics, Vanderbilt University, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A5">Vanderbilt Vaccine Research Program, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Vanderbilt Vaccine Research Program, Vanderbilt University, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation></author><author><name sortKey="Lee, David" sort="Lee, David" uniqKey="Lee D" first="David" last="Lee">David Lee</name><affiliation wicri:level="2"><nlm:aff id="A6">Department of Medicine and Biomedical Sciences Graduate Program, School of Medicine, UCSD, San Diego, California, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Medicine and Biomedical Sciences Graduate Program, School of Medicine, UCSD, San Diego, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Li, Sheng" sort="Li, Sheng" uniqKey="Li S" first="Sheng" last="Li">Sheng Li</name><affiliation wicri:level="2"><nlm:aff id="A6">Department of Medicine and Biomedical Sciences Graduate Program, School of Medicine, UCSD, San Diego, California, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Medicine and Biomedical Sciences Graduate Program, School of Medicine, UCSD, San Diego, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></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="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><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Integrative Structural and Computational Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></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 wicri:level="2"><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><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Medicine, Division of Infectious Diseases at Icahn School of Medicine at Mount Sinai (ISMMS), New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></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 wicri:level="2"><nlm:aff id="A2">Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Pediatrics, Vanderbilt University, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation><affiliation><nlm:aff wicri:cut=", and" id="A4">Departments of Pathology, Microbiology, and Immunology</nlm:aff><wicri:noCountry code="subfield">and Immunology</wicri:noCountry></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><affiliations><list><country><li>États-Unis</li></country><region><li>Californie</li><li>Tennessee</li><li>État de New York</li></region></list><tree><noCountry><name sortKey="Albrecht, Randy A" sort="Albrecht, Randy A" uniqKey="Albrecht R" first="Randy A." last="Albrecht">Randy A. Albrecht</name><name sortKey="Bangaru, Sandhya" sort="Bangaru, Sandhya" uniqKey="Bangaru S" first="Sandhya" last="Bangaru">Sandhya Bangaru</name><name sortKey="Bombardi, Robin G" sort="Bombardi, Robin G" uniqKey="Bombardi R" first="Robin G." last="Bombardi">Robin G. Bombardi</name><name sortKey="Branchizio, Andre" sort="Branchizio, Andre" uniqKey="Branchizio A" first="Andre" last="Branchizio">Andre Branchizio</name><name sortKey="Graham, Stephen" sort="Graham, Stephen" uniqKey="Graham S" first="Stephen" last="Graham">Stephen Graham</name><name sortKey="Kose, Nurgun" sort="Kose, Nurgun" uniqKey="Kose N" first="Nurgun" last="Kose">Nurgun Kose</name><name sortKey="Lampley, Rebecca M" sort="Lampley, Rebecca M" uniqKey="Lampley R" first="Rebecca M." last="Lampley">Rebecca M. Lampley</name><name sortKey="Yu, Yingchun" sort="Yu, Yingchun" uniqKey="Yu Y" first="Yingchun" last="Yu">Yingchun Yu</name></noCountry><country name="États-Unis"><region name="Tennessee"><name sortKey="Thornburg, Natalie J" sort="Thornburg, Natalie J" uniqKey="Thornburg N" first="Natalie J." last="Thornburg">Natalie J. Thornburg</name></region><name sortKey="Creech, C Buddy" sort="Creech, C Buddy" uniqKey="Creech C" first="C. Buddy" last="Creech">C. Buddy Creech</name><name sortKey="Creech, C Buddy" sort="Creech, C Buddy" uniqKey="Creech C" first="C. Buddy" last="Creech">C. Buddy Creech</name><name sortKey="Crowe, James E" sort="Crowe, James E" uniqKey="Crowe J" first="James E." last="Crowe">James E. Crowe</name><name sortKey="Edwards, Kathryn M" sort="Edwards, Kathryn M" uniqKey="Edwards K" first="Kathryn M." last="Edwards">Kathryn M. Edwards</name><name sortKey="Edwards, Kathryn M" sort="Edwards, Kathryn M" uniqKey="Edwards K" first="Kathryn M." last="Edwards">Kathryn M. Edwards</name><name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="García-Sastre">Adolfo García-Sastre</name><name sortKey="Lee, David" sort="Lee, David" uniqKey="Lee D" first="David" last="Lee">David Lee</name><name sortKey="Li, Sheng" sort="Li, Sheng" uniqKey="Li S" first="Sheng" last="Li">Sheng Li</name><name sortKey="Rock, Michael T" sort="Rock, Michael T" uniqKey="Rock M" first="Michael T." last="Rock">Michael T. Rock</name><name sortKey="Rock, Michael T" sort="Rock, Michael T" uniqKey="Rock M" first="Michael T." last="Rock">Michael T. Rock</name><name sortKey="Sapparapu, Gopal" sort="Sapparapu, Gopal" uniqKey="Sapparapu G" first="Gopal" last="Sapparapu">Gopal Sapparapu</name><name sortKey="Wilson, Ian A" sort="Wilson, Ian A" uniqKey="Wilson I" first="Ian A." last="Wilson">Ian A. Wilson</name><name sortKey="Yoder, Sandra M" sort="Yoder, Sandra M" uniqKey="Yoder S" first="Sandra M." last="Yoder">Sandra M. Yoder</name><name sortKey="Zhang, Heng" sort="Zhang, Heng" uniqKey="Zhang H" first="Heng" last="Zhang">Heng Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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