Evaluation of a recombination-resistant coronavirus as a broadly applicable, rapidly implementable vaccine platform
Identifieur interne : 000C86 ( Main/Exploration ); précédent : 000C85; suivant : 000C87Evaluation 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
Affiliations:
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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 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V">VD Menachery</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yount, B" uniqKey="Yount B">B Yount</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Becker, Mm" uniqKey="Becker M">MM Becker</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Caroline du Nord</li><li>Maryland</li></region></list><tree><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Graham, Rachel L" sort="Graham, Rachel L" uniqKey="Graham R" first="Rachel L." last="Graham">Rachel L. Graham</name></region><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><name sortKey="Deming, Damon J" sort="Deming, Damon J" uniqKey="Deming D" first="Damon J." last="Deming">Damon J. Deming</name><name sortKey="Deming, Damon J" sort="Deming, Damon J" uniqKey="Deming D" first="Damon J." last="Deming">Damon J. Deming</name><name sortKey="Deming, Damon J" sort="Deming, Damon J" uniqKey="Deming D" first="Damon J." last="Deming">Damon J. Deming</name><name sortKey="Deming, Meagan E" sort="Deming, Meagan E" uniqKey="Deming M" first="Meagan E." last="Deming">Meagan E. Deming</name><name sortKey="Deming, Meagan E" sort="Deming, Meagan E" uniqKey="Deming M" first="Meagan E." last="Deming">Meagan E. Deming</name><name sortKey="Yount, Boyd L" sort="Yount, Boyd L" uniqKey="Yount B" first="Boyd L." last="Yount">Boyd L. Yount</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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