Double-layered protein nanoparticles induce broad protection against divergent influenza A viruses
Identifieur interne : 000187 ( Pmc/Curation ); précédent : 000186; suivant : 000188Double-layered protein nanoparticles induce broad protection against divergent influenza A viruses
Auteurs : Lei Deng [États-Unis] ; Teena Mohan [États-Unis] ; Timothy Z. Chang [États-Unis] ; Gilbert X. Gonzalez [États-Unis] ; Ye Wang [États-Unis] ; Young-Man Kwon [États-Unis] ; Sang-Moo Kang [États-Unis] ; Richard W. Compans [États-Unis] ; Julie A. Champion [États-Unis] ; Bao-Zhong Wang [États-Unis]Source :
- Nature Communications [ 2041-1723 ] ; 2018.
Abstract
Current influenza vaccines provide limited protection against circulating influenza A viruses. A universal influenza vaccine will eliminate the intrinsic limitations of the seasonal flu vaccines. Here we report methodology to generate double-layered protein nanoparticles as a universal influenza vaccine. Layered nanoparticles are fabricated by desolvating tetrameric M2e into protein nanoparticle cores and coating these cores by crosslinking headless HAs. Representative headless HAs of two HA phylogenetic groups are constructed and purified. Vaccinations with the resulting protein nanoparticles in mice induces robust long-lasting immunity, fully protecting the mice against challenges by divergent influenza A viruses of the same group or both groups. The results demonstrate the importance of incorporating both structure-stabilized HA stalk domains and M2e into a universal influenza vaccine to improve its protective potency and breadth. These potent disassemblable protein nanoparticles indicate a wide application in protein drug delivery and controlled release.
Url:
DOI: 10.1038/s41467-017-02725-4
PubMed: 29367723
PubMed Central: 5783933
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A universal influenza vaccine will eliminate the intrinsic limitations of the seasonal flu vaccines. Here we report methodology to generate double-layered protein nanoparticles as a universal influenza vaccine. Layered nanoparticles are fabricated by desolvating tetrameric M2e into protein nanoparticle cores and coating these cores by crosslinking headless HAs. Representative headless HAs of two HA phylogenetic groups are constructed and purified. Vaccinations with the resulting protein nanoparticles in mice induces robust long-lasting immunity, fully protecting the mice against challenges by divergent influenza A viruses of the same group or both groups. The results demonstrate the importance of incorporating both structure-stabilized HA stalk domains and M2e into a universal influenza vaccine to improve its protective potency and breadth. These potent disassemblable protein nanoparticles indicate a wide application in protein drug delivery and controlled release.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Pica, N" uniqKey="Pica N">N Pica</name></author><author><name sortKey="Palese, P" uniqKey="Palese P">P Palese</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dawood, Fs" uniqKey="Dawood F">FS Dawood</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chambers, Bs" uniqKey="Chambers B">BS Chambers</name></author><author><name sortKey="Parkhouse, K" uniqKey="Parkhouse K">K Parkhouse</name></author><author><name sortKey="Ross, Tm" uniqKey="Ross T">TM Ross</name></author><author><name sortKey="Alby, K" uniqKey="Alby K">K Alby</name></author><author><name sortKey="Hensley, Se" uniqKey="Hensley S">SE Hensley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ohmit, 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Nat Commun</journal-id><journal-id journal-id-type="iso-abbrev">Nat Commun</journal-id><journal-title-group><journal-title>Nature Communications</journal-title></journal-title-group><issn pub-type="epub">2041-1723</issn><publisher><publisher-name>Nature Publishing Group UK</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">29367723</article-id><article-id pub-id-type="pmc">5783933</article-id><article-id pub-id-type="publisher-id">2725</article-id><article-id pub-id-type="doi">10.1038/s41467-017-02725-4</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Double-layered protein nanoparticles induce broad protection against divergent influenza A viruses</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Deng</surname><given-names>Lei</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Mohan</surname><given-names>Teena</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Chang</surname><given-names>Timothy Z.</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Gonzalez</surname><given-names>Gilbert X.</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Ye</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Kwon</surname><given-names>Young-Man</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Kang</surname><given-names>Sang-Moo</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Compans</surname><given-names>Richard W.</given-names></name><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Champion</surname><given-names>Julie A.</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-1561-4318</contrib-id><name><surname>Wang</surname><given-names>Bao-Zhong</given-names></name><address><email>bwang23@gsu.edu</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 7400</institution-id><institution-id institution-id-type="GRID">grid.256304.6</institution-id><institution>Center for Inflammation, Immunity & Infection,</institution><institution>Georgia State University,</institution></institution-wrap>Atlanta, GA 30303 USA</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2097 4943</institution-id><institution-id institution-id-type="GRID">grid.213917.f</institution-id><institution>School of Chemical & Biomolecular Engineering,</institution><institution>Georgia Institute of Technology,</institution></institution-wrap>Atlanta, GA 30332 USA</aff><aff id="Aff3"><label>3</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0941 6502</institution-id><institution-id institution-id-type="GRID">grid.189967.8</institution-id><institution>Department of Microbiology and Immunology and Emory Vaccine Center,</institution><institution>Emory University School of Medicine,</institution></institution-wrap>Atlanta, GA 30322 USA</aff></contrib-group><pub-date pub-type="epub"><day>24</day><month>1</month><year>2018</year></pub-date><pub-date pub-type="pmc-release"><day>24</day><month>1</month><year>2018</year></pub-date><pub-date pub-type="collection"><year>2018</year></pub-date><volume>9</volume><elocation-id>359</elocation-id><history><date date-type="received"><day>13</day><month>7</month><year>2017</year></date><date date-type="accepted"><day>20</day><month>12</month><year>2017</year></date></history><permissions><copyright-statement>© The Author(s) 2018</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold> This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>.</license-p></license></permissions><abstract id="Abs1"><p id="Par1">Current influenza vaccines provide limited protection against circulating influenza A viruses. A universal influenza vaccine will eliminate the intrinsic limitations of the seasonal flu vaccines. Here we report methodology to generate double-layered protein nanoparticles as a universal influenza vaccine. Layered nanoparticles are fabricated by desolvating tetrameric M2e into protein nanoparticle cores and coating these cores by crosslinking headless HAs. Representative headless HAs of two HA phylogenetic groups are constructed and purified. Vaccinations with the resulting protein nanoparticles in mice induces robust long-lasting immunity, fully protecting the mice against challenges by divergent influenza A viruses of the same group or both groups. The results demonstrate the importance of incorporating both structure-stabilized HA stalk domains and M2e into a universal influenza vaccine to improve its protective potency and breadth. These potent disassemblable protein nanoparticles indicate a wide application in protein drug delivery and controlled release.</p></abstract><abstract id="Abs2" abstract-type="web-summary"><p id="Par2">Relatively well conserved domains of influenza A virus (IAV) proteins are potential candidates for the development of a universal IAV vaccine. Here, Deng <italic>et al</italic>. combine two such conserved antigens (M2e and HA stalk) in a double-layered protein nanoparticle and show that it protects against divergent IAVs in mice.</p></abstract><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2018</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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