Double-layered protein nanoparticles induce broad protection against divergent influenza A viruses
Identifieur interne : 000206 ( Main/Exploration ); précédent : 000205; suivant : 000207Double-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
Affiliations:
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Champion</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><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</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Géorgie (États-Unis)</region></placeName><wicri:cityArea>Atlanta</wicri:cityArea></affiliation></author><author><name sortKey="Wang, Bao Zhong" sort="Wang, Bao Zhong" uniqKey="Wang B" first="Bao-Zhong" last="Wang">Bao-Zhong Wang</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><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</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Géorgie (États-Unis)</region></placeName><wicri:cityArea>Atlanta</wicri:cityArea></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><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></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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uniqKey="Champion J" first="Julie A." last="Champion">Julie A. Champion</name><name sortKey="Chang, Timothy Z" sort="Chang, Timothy Z" uniqKey="Chang T" first="Timothy Z." last="Chang">Timothy Z. Chang</name><name sortKey="Compans, Richard W" sort="Compans, Richard W" uniqKey="Compans R" first="Richard W." last="Compans">Richard W. Compans</name><name sortKey="Gonzalez, Gilbert X" sort="Gonzalez, Gilbert X" uniqKey="Gonzalez G" first="Gilbert X." last="Gonzalez">Gilbert X. Gonzalez</name><name sortKey="Kang, Sang Moo" sort="Kang, Sang Moo" uniqKey="Kang S" first="Sang-Moo" last="Kang">Sang-Moo Kang</name><name sortKey="Kwon, Young Man" sort="Kwon, Young Man" uniqKey="Kwon Y" first="Young-Man" last="Kwon">Young-Man Kwon</name><name sortKey="Mohan, Teena" sort="Mohan, Teena" uniqKey="Mohan T" first="Teena" last="Mohan">Teena Mohan</name><name sortKey="Wang, Bao Zhong" sort="Wang, Bao Zhong" uniqKey="Wang B" first="Bao-Zhong" last="Wang">Bao-Zhong Wang</name><name sortKey="Wang, Ye" sort="Wang, Ye" uniqKey="Wang Y" first="Ye" last="Wang">Ye Wang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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