Multistate design of influenza antibodies improves affinity and breadth against seasonal viruses
Identifieur interne : 000065 ( Main/Exploration ); précédent : 000064; suivant : 000066Multistate design of influenza antibodies improves affinity and breadth against seasonal viruses
Auteurs : Alexander M. Sevy ; Nicholas C. Wu ; Iuliia M. Gilchuk ; Erica H. Parrish ; Sebastian Burger [Allemagne] ; Dina Yousif ; Marcus B. M. Nagel ; Kevin L. Schey ; Ian A. Wilson ; James E. Crowe ; Jens MeilerSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2019.
Abstract
Influenza is an annual threat to global public health, in part because of constant antigenic drift that facilitates evasion of the antibody response. Rapid changes in the influenza HA protein make it difficult for an antibody to achieve broad activity against different virus subtypes. We developed a computational method that can optimize an antibody sequence to be robust against seasonal variation. As a proof of concept, we tested this method by redesigning a known antibody against a set of diverse HA antigens and showed that the variant redesigned antibodies have improved activity against the virus panel, as predicted. This work shows that computational design can improve naturally occurring antibodies for recognition of different virus strains.
Url:
DOI: 10.1073/pnas.1806004116
PubMed: 30642961
PubMed Central: 6358683
Affiliations:
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Sevy</name><affiliation><nlm:aff id="aff1">Chemical & Physical Biology Program,<institution>Vanderbilt University</institution>, Nashville,<addr-line>TN</addr-line> 37235;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Center for Structural Biology,<institution>Vanderbilt University</institution>, Nashville,<addr-line>TN</addr-line> 37235;</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Vanderbilt Vaccine Center,<institution>Vanderbilt University Medical Center</institution>, Nashville,<addr-line>TN</addr-line> 37232;</nlm:aff></affiliation></author><author><name sortKey="Wu, Nicholas C" sort="Wu, Nicholas C" uniqKey="Wu N" first="Nicholas C." last="Wu">Nicholas C. Wu</name><affiliation><nlm:aff id="aff4">Department of Integrative Structural and Computational Biology,<institution>The Scripps Research Institute</institution>, La Jolla,<addr-line>CA</addr-line> 92037;</nlm:aff></affiliation></author><author><name sortKey="Gilchuk, Iuliia M" sort="Gilchuk, Iuliia M" uniqKey="Gilchuk I" first="Iuliia M." last="Gilchuk">Iuliia M. Gilchuk</name><affiliation><nlm:aff id="aff3">Vanderbilt Vaccine Center,<institution>Vanderbilt University Medical Center</institution>, Nashville,<addr-line>TN</addr-line> 37232;</nlm:aff></affiliation></author><author><name sortKey="Parrish, Erica H" sort="Parrish, Erica H" uniqKey="Parrish E" first="Erica H." last="Parrish">Erica H. Parrish</name><affiliation><nlm:aff id="aff3">Vanderbilt Vaccine Center,<institution>Vanderbilt University Medical Center</institution>, Nashville,<addr-line>TN</addr-line> 37232;</nlm:aff></affiliation></author><author><name sortKey="Burger, Sebastian" sort="Burger, Sebastian" uniqKey="Burger S" first="Sebastian" last="Burger">Sebastian Burger</name><affiliation wicri:level="1"><nlm:aff id="aff5">Department of Mathematics,<institution>University of Leipzig</institution>, 04109 Leipzig,<country>Germany</country>;</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yousif, Dina" sort="Yousif, Dina" uniqKey="Yousif D" first="Dina" last="Yousif">Dina Yousif</name><affiliation><nlm:aff id="aff3">Vanderbilt Vaccine Center,<institution>Vanderbilt University Medical Center</institution>, Nashville,<addr-line>TN</addr-line> 37232;</nlm:aff></affiliation></author><author><name sortKey="Nagel, Marcus B M" sort="Nagel, Marcus B M" uniqKey="Nagel M" first="Marcus B. M." last="Nagel">Marcus B. M. Nagel</name><affiliation><nlm:aff id="aff2">Center for Structural Biology,<institution>Vanderbilt University</institution>, Nashville,<addr-line>TN</addr-line> 37235;</nlm:aff></affiliation><affiliation><nlm:aff id="aff6">Vanderbilt Mass Spectrometry Research Center and Department of Biochemistry,<institution>Vanderbilt University School of Medicine</institution>, Nashville,<addr-line>TN</addr-line> 37232;</nlm:aff></affiliation></author><author><name sortKey="Schey, Kevin L" sort="Schey, Kevin L" uniqKey="Schey K" first="Kevin L." last="Schey">Kevin L. Schey</name><affiliation><nlm:aff id="aff6">Vanderbilt Mass Spectrometry Research Center and Department of Biochemistry,<institution>Vanderbilt University School of Medicine</institution>, Nashville,<addr-line>TN</addr-line> 37232;</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="aff4">Department of Integrative Structural and Computational Biology,<institution>The Scripps Research Institute</institution>, La Jolla,<addr-line>CA</addr-line> 92037;</nlm:aff></affiliation><affiliation><nlm:aff id="aff7">The Skaggs Institute for Chemical Biology,<institution>The Scripps Research Institute</institution>, La Jolla,<addr-line>CA</addr-line> 92037;</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 id="aff1">Chemical & Physical Biology Program,<institution>Vanderbilt University</institution>, Nashville,<addr-line>TN</addr-line> 37235;</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Vanderbilt Vaccine Center,<institution>Vanderbilt University Medical Center</institution>, Nashville,<addr-line>TN</addr-line> 37232;</nlm:aff></affiliation><affiliation><nlm:aff id="aff8">Department of Pediatrics,<institution>Vanderbilt University Medical Center</institution>, Nashville,<addr-line>TN</addr-line> 37232;</nlm:aff></affiliation></author><author><name sortKey="Meiler, Jens" sort="Meiler, Jens" uniqKey="Meiler J" first="Jens" last="Meiler">Jens Meiler</name><affiliation><nlm:aff id="aff1">Chemical & Physical Biology Program,<institution>Vanderbilt University</institution>, Nashville,<addr-line>TN</addr-line> 37235;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Center for Structural Biology,<institution>Vanderbilt University</institution>, Nashville,<addr-line>TN</addr-line> 37235;</nlm:aff></affiliation><affiliation><nlm:aff id="aff9">Department of Chemistry,<institution>Vanderbilt University</institution>, Nashville,<addr-line>TN</addr-line> 37235</nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Significance</title><p>Influenza is an annual threat to global public health, in part because of constant antigenic drift that facilitates evasion of the antibody response. Rapid changes in the influenza HA protein make it difficult for an antibody to achieve broad activity against different virus subtypes. We developed a computational method that can optimize an antibody sequence to be robust against seasonal variation. As a proof of concept, we tested this method by redesigning a known antibody against a set of diverse HA antigens and showed that the variant redesigned antibodies have improved activity against the virus panel, as predicted. This work shows that computational design can improve naturally occurring antibodies for recognition of different virus strains.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Rolfes, Ma" uniqKey="Rolfes M">MA Rolfes</name></author><author><name sortKey="Foppa, Im" uniqKey="Foppa I">IM Foppa</name></author><author><name sortKey="Garg, S" uniqKey="Garg S">S Garg</name></author><author><name sortKey="Flannery, B" uniqKey="Flannery B">B Flannery</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Belongia, Ea" uniqKey="Belongia E">EA Belongia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ekiert, Dc" uniqKey="Ekiert D">DC Ekiert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Krause, Jc" uniqKey="Krause J">JC Krause</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Whittle, Jrr" uniqKey="Whittle 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uniqKey="Ionescu R">RM Ionescu</name></author><author><name sortKey="Vlasak, J" uniqKey="Vlasak J">J Vlasak</name></author><author><name sortKey="Price, C" uniqKey="Price C">C Price</name></author><author><name sortKey="Kirchmeier, M" uniqKey="Kirchmeier M">M Kirchmeier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Willis, Jr" uniqKey="Willis J">JR Willis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Babor, M" uniqKey="Babor M">M Babor</name></author><author><name sortKey="Kortemme, T" uniqKey="Kortemme T">T Kortemme</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Havranek, Jj" uniqKey="Havranek J">JJ Havranek</name></author><author><name sortKey="Harbury, Pb" uniqKey="Harbury P">PB Harbury</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lewis, Sm" uniqKey="Lewis S">SM 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Crowe</name><name sortKey="Gilchuk, Iuliia M" sort="Gilchuk, Iuliia M" uniqKey="Gilchuk I" first="Iuliia M." last="Gilchuk">Iuliia M. Gilchuk</name><name sortKey="Meiler, Jens" sort="Meiler, Jens" uniqKey="Meiler J" first="Jens" last="Meiler">Jens Meiler</name><name sortKey="Nagel, Marcus B M" sort="Nagel, Marcus B M" uniqKey="Nagel M" first="Marcus B. M." last="Nagel">Marcus B. M. Nagel</name><name sortKey="Parrish, Erica H" sort="Parrish, Erica H" uniqKey="Parrish E" first="Erica H." last="Parrish">Erica H. Parrish</name><name sortKey="Schey, Kevin L" sort="Schey, Kevin L" uniqKey="Schey K" first="Kevin L." last="Schey">Kevin L. Schey</name><name sortKey="Sevy, Alexander M" sort="Sevy, Alexander M" uniqKey="Sevy A" first="Alexander M." last="Sevy">Alexander M. Sevy</name><name sortKey="Wilson, Ian A" sort="Wilson, Ian A" uniqKey="Wilson I" first="Ian A." last="Wilson">Ian A. Wilson</name><name sortKey="Wu, Nicholas C" sort="Wu, Nicholas C" uniqKey="Wu N" first="Nicholas C." last="Wu">Nicholas C. Wu</name><name sortKey="Yousif, Dina" sort="Yousif, Dina" uniqKey="Yousif D" first="Dina" last="Yousif">Dina Yousif</name></noCountry><country name="Allemagne"><noRegion><name sortKey="Burger, Sebastian" sort="Burger, Sebastian" uniqKey="Burger S" first="Sebastian" last="Burger">Sebastian Burger</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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