Evaluation of a recombination-resistant coronavirus as a broadly applicable, rapidly implementable vaccine platform
Identifieur interne : 000358 ( Pmc/Curation ); précédent : 000357; suivant : 000359Evaluation of a recombination-resistant coronavirus as a broadly applicable, rapidly implementable vaccine platform
Auteurs : Rachel L. Graham [États-Unis] ; Damon J. Deming [États-Unis] ; Meagan E. Deming [États-Unis] ; Boyd L. Yount [États-Unis] ; Ralph S. Baric [États-Unis]Source :
- Communications Biology [ 2399-3642 ] ; 2018.
Abstract
Emerging and re-emerging zoonotic viral diseases are major threats to global health, economic stability, and national security. Vaccines are key for reducing coronaviral disease burden; however, the utility of live-attenuated vaccines is limited by risks of reversion or repair. Because of their history of emergence events due to their prevalence in zoonotic pools, designing live-attenuated coronavirus vaccines that can be rapidly and broadly implemented is essential for outbreak preparedness. Here, we show that coronaviruses with completely rewired transcription regulatory networks (TRNs) are effective vaccines against SARS-CoV. The TRN-rewired viruses are attenuated and protect against lethal SARS-CoV challenge. While a 3-nt rewired TRN reverts via second-site mutation upon serial passage, a 7-nt rewired TRN is more stable, suggesting that a more extensively rewired TRN might be essential for avoiding growth selection. In summary, rewiring the TRN is a feasible strategy for limiting reversion in an effective live-attenuated coronavirus vaccine candidate that is potentially portable across the Nidovirales order.
Url:
DOI: 10.1038/s42003-018-0175-7
PubMed: 30393776
PubMed Central: 6206136
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Baric</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000000122483208</institution-id><institution-id institution-id-type="GRID">grid.10698.36</institution-id><institution>Department of Epidemiology,</institution><institution>The University of North Carolina at Chapel Hill,</institution></institution-wrap>2107 McGavran-Greenberg, CB 7435, Chapel Hill, NC 27599 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>2107 McGavran-Greenberg, CB 7435, Chapel Hill</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000000122483208</institution-id><institution-id institution-id-type="GRID">grid.10698.36</institution-id><institution>Department of Microbiology and Immunology,</institution><institution>The University of North Carolina at Chapel Hill,</institution></institution-wrap>Chapel Hill, NC 27599 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Chapel Hill</wicri:cityArea></affiliation></author></analytic><series><title level="j">Communications Biology</title><idno type="eISSN">2399-3642</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">Emerging and re-emerging zoonotic viral diseases are major threats to global health, economic stability, and national security. Vaccines are key for reducing coronaviral disease burden; however, the utility of live-attenuated vaccines is limited by risks of reversion or repair. Because of their history of emergence events due to their prevalence in zoonotic pools, designing live-attenuated coronavirus vaccines that can be rapidly and broadly implemented is essential for outbreak preparedness. Here, we show that coronaviruses with completely rewired transcription regulatory networks (TRNs) are effective vaccines against SARS-CoV. The TRN-rewired viruses are attenuated and protect against lethal SARS-CoV challenge. While a 3-nt rewired TRN reverts via second-site mutation upon serial passage, a 7-nt rewired TRN is more stable, suggesting that a more extensively rewired TRN might be essential for avoiding growth selection. In summary, rewiring the TRN is a feasible strategy for limiting reversion in an effective live-attenuated coronavirus vaccine candidate that is potentially portable across the Nidovirales order.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Graham, Rl" uniqKey="Graham R">RL Graham</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Graham, Rl" uniqKey="Graham R">RL Graham</name></author><author><name sortKey="Donaldson, Ef" uniqKey="Donaldson E">EF Donaldson</name></author><author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jones, Ke" uniqKey="Jones K">KE Jones</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Morens, Dm" uniqKey="Morens D">DM Morens</name></author><author><name sortKey="Fauci, As" uniqKey="Fauci A">AS Fauci</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sessa, R" uniqKey="Sessa R">R Sessa</name></author><author><name sortKey="Palagiano, C" uniqKey="Palagiano C">C Palagiano</name></author><author><name sortKey="Scifoni, Mg" uniqKey="Scifoni M">MG Scifoni</name></author><author><name sortKey="Di Pietro, M" uniqKey="Di Pietro M">M di Pietro</name></author><author><name sortKey="Del Piano, M" uniqKey="Del Piano M">M Del Piano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Karesh, Wb" uniqKey="Karesh W">WB Karesh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kreuder Johnson, C" uniqKey="Kreuder Johnson C">C Kreuder Johnson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Tawfiq, Ja" uniqKey="Al Tawfiq J">JA 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sortKey="Roberts, Rs" uniqKey="Roberts R">RS Roberts</name></author><author><name sortKey="Lindesmith, L" uniqKey="Lindesmith L">L Lindesmith</name></author><author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zuniga, S" uniqKey="Zuniga S">S Zuniga</name></author><author><name sortKey="Sola, I" uniqKey="Sola I">I Sola</name></author><author><name sortKey="Alonso, S" uniqKey="Alonso S">S Alonso</name></author><author><name sortKey="Enjuanes, L" uniqKey="Enjuanes L">L Enjuanes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sheahan, T" uniqKey="Sheahan T">T Sheahan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Graham, Rl" uniqKey="Graham R">RL Graham</name></author><author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Consortium, Csme" 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Commun Biol</journal-id><journal-id journal-id-type="iso-abbrev">Commun Biol</journal-id><journal-title-group><journal-title>Communications Biology</journal-title></journal-title-group><issn pub-type="epub">2399-3642</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">30393776</article-id><article-id pub-id-type="pmc">6206136</article-id><article-id pub-id-type="publisher-id">175</article-id><article-id pub-id-type="doi">10.1038/s42003-018-0175-7</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Evaluation of a recombination-resistant coronavirus as a broadly applicable, rapidly implementable vaccine platform</article-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-3143-6515</contrib-id><name><surname>Graham</surname><given-names>Rachel L.</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Deming</surname><given-names>Damon J.</given-names></name><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Deming</surname><given-names>Meagan E.</given-names></name><xref ref-type="aff" rid="Aff2">2</xref><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Yount</surname><given-names>Boyd L.</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Baric</surname><given-names>Ralph S.</given-names></name><address><email>rbaric@ad.unc.edu</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="ISNI">0000000122483208</institution-id><institution-id institution-id-type="GRID">grid.10698.36</institution-id><institution>Department of Epidemiology,</institution><institution>The University of North Carolina at Chapel Hill,</institution></institution-wrap>2107 McGavran-Greenberg, CB 7435, Chapel Hill, NC 27599 USA</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="ISNI">0000000122483208</institution-id><institution-id institution-id-type="GRID">grid.10698.36</institution-id><institution>Department of Microbiology and Immunology,</institution><institution>The University of North Carolina at Chapel Hill,</institution></institution-wrap>Chapel Hill, NC 27599 USA</aff><aff id="Aff3"><label>3</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2243 3366</institution-id><institution-id institution-id-type="GRID">grid.417587.8</institution-id><institution>Present Address: Food and Drug Administration, 10933 New Hampshire Avenue,</institution></institution-wrap>Bldg 22, Rm 6170, Silver Spring, MD 20993 USA</aff><aff id="Aff4"><label>4</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2175 4264</institution-id><institution-id institution-id-type="GRID">grid.411024.2</institution-id><institution>Present Address: University of Maryland Medical Center, Department of Medicine, Division of Infectious Disease,</institution><institution>Institute of Human Virology,</institution></institution-wrap>725 West Lombard Street, Room 211A, Baltimore, MD 21201 USA</aff></contrib-group><pub-date pub-type="epub"><day>29</day><month>10</month><year>2018</year></pub-date><pub-date pub-type="pmc-release"><day>29</day><month>10</month><year>2018</year></pub-date><pub-date pub-type="collection"><year>2018</year></pub-date><volume>1</volume><elocation-id>179</elocation-id><history><date date-type="received"><day>31</day><month>1</month><year>2018</year></date><date date-type="accepted"><day>19</day><month>9</month><year>2018</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">Emerging and re-emerging zoonotic viral diseases are major threats to global health, economic stability, and national security. Vaccines are key for reducing coronaviral disease burden; however, the utility of live-attenuated vaccines is limited by risks of reversion or repair. Because of their history of emergence events due to their prevalence in zoonotic pools, designing live-attenuated coronavirus vaccines that can be rapidly and broadly implemented is essential for outbreak preparedness. Here, we show that coronaviruses with completely rewired transcription regulatory networks (TRNs) are effective vaccines against SARS-CoV. The TRN-rewired viruses are attenuated and protect against lethal SARS-CoV challenge. While a 3-nt rewired TRN reverts via second-site mutation upon serial passage, a 7-nt rewired TRN is more stable, suggesting that a more extensively rewired TRN might be essential for avoiding growth selection. In summary, rewiring the TRN is a feasible strategy for limiting reversion in an effective live-attenuated coronavirus vaccine candidate that is potentially portable across the Nidovirales order.</p></abstract><abstract id="Abs2" abstract-type="web-summary"><p id="Par2">Rachel Graham et al. show that coronaviruses with extensively rewired transcription regulatory networks are effective vaccine candidates against Severe Acute Respiratory Syndrome Coronavirus. The reversion of live-attenuated vaccine strains to virulence can be avoided with these vaccines.</p></abstract><kwd-group kwd-group-type="npg-subject"><title>Subject terms</title><kwd>SARS virus</kwd><kwd>Live attenuated vaccines</kwd><kwd>Transcriptional regulatory elements</kwd><kwd>Viral genetics</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/100006955</institution-id><institution>Office of Extramural Research, National Institutes of Health (OER)</institution></institution-wrap></funding-source><award-id>5F32AI080148</award-id><award-id>U19-AI107810</award-id><award-id>R01-AI108197</award-id><award-id>U54-AI057157</award-id><principal-award-recipient><name><surname>Graham</surname><given-names>Rachel L.</given-names></name><name><surname>Baric</surname><given-names>Ralph S.</given-names></name></principal-award-recipient></award-group></funding-group><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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