Evaluation of a recombination-resistant coronavirus as a broadly applicable, rapidly implementable vaccine platform.
Identifieur interne : 000961 ( PubMed/Curation ); précédent : 000960; suivant : 000962Evaluation 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.
DOI: 10.1038/s42003-018-0175-7
PubMed: 30393776
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Deming</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599</wicri:regionArea></affiliation></author><author><name sortKey="Yount, Boyd L" sort="Yount, Boyd L" uniqKey="Yount B" first="Boyd L" last="Yount">Boyd L. Yount</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology, The University of North Carolina at Chapel Hill, 2107 McGavran-Greenberg, CB 7435, Chapel Hill, NC, 27599, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, The University of North Carolina at Chapel Hill, 2107 McGavran-Greenberg, CB 7435, Chapel Hill, NC, 27599</wicri:regionArea></affiliation></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology, The University of North Carolina at Chapel Hill, 2107 McGavran-Greenberg, CB 7435, Chapel Hill, NC, 27599, USA. rbaric@ad.unc.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, The University of North Carolina at Chapel Hill, 2107 McGavran-Greenberg, CB 7435, Chapel Hill, NC, 27599</wicri:regionArea></affiliation></author></analytic><series><title level="j">Communications biology</title><idno type="eISSN">2399-3642</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">30393776</PMID><DateRevised><Year>2020</Year><Month>03</Month><Day>26</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">2399-3642</ISSN><JournalIssue CitedMedium="Internet"><Volume>1</Volume><PubDate><Year>2018</Year></PubDate></JournalIssue><Title>Communications biology</Title><ISOAbbreviation>Commun Biol</ISOAbbreviation></Journal><ArticleTitle>Evaluation of a recombination-resistant coronavirus as a broadly applicable, rapidly implementable vaccine platform.</ArticleTitle><Pagination><MedlinePgn>179</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/s42003-018-0175-7</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Graham</LastName><ForeName>Rachel L</ForeName><Initials>RL</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-3143-6515</Identifier><AffiliationInfo><Affiliation>Department of Epidemiology, The University of North Carolina at Chapel Hill, 2107 McGavran-Greenberg, CB 7435, Chapel Hill, NC, 27599, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Deming</LastName><ForeName>Damon J</ForeName><Initials>DJ</Initials><AffiliationInfo><Affiliation>Department of Epidemiology, The University of North Carolina at Chapel Hill, 2107 McGavran-Greenberg, CB 7435, Chapel Hill, NC, 27599, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Food and Drug Administration, 10933 New Hampshire Avenue, Bldg 22, Rm 6170, Silver Spring, MD, 20993, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Deming</LastName><ForeName>Meagan E</ForeName><Initials>ME</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>University of Maryland Medical Center, Department of Medicine, Division of Infectious Disease, Institute of Human Virology, 725 West Lombard Street, Room 211A, Baltimore, MD, 21201, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yount</LastName><ForeName>Boyd L</ForeName><Initials>BL</Initials><AffiliationInfo><Affiliation>Department of Epidemiology, The University of North Carolina at Chapel Hill, 2107 McGavran-Greenberg, CB 7435, Chapel Hill, NC, 27599, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Baric</LastName><ForeName>Ralph S</ForeName><Initials>RS</Initials><AffiliationInfo><Affiliation>Department of Epidemiology, The University of North Carolina at Chapel Hill, 2107 McGavran-Greenberg, CB 7435, Chapel Hill, NC, 27599, USA. rbaric@ad.unc.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. rbaric@ad.unc.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>F32 AI080148</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI108197</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United 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