Combination Attenuation Offers Strategy for Live Attenuated Coronavirus Vaccines.
Identifieur interne : 001E90 ( Ncbi/Merge ); précédent : 001E89; suivant : 001E91Combination Attenuation Offers Strategy for Live Attenuated Coronavirus Vaccines.
Auteurs : Vineet D. Menachery [États-Unis] ; Lisa E. Gralinski [États-Unis] ; Hugh D. Mitchell [États-Unis] ; Kenneth H. Dinnon [États-Unis] ; Sarah R. Leist [États-Unis] ; Boyd L. Yount [États-Unis] ; Eileen T. Mcanarney [États-Unis] ; Rachel L. Graham [États-Unis] ; Katrina M. Waters [États-Unis] ; Ralph S. Baric [États-Unis]Source :
- Journal of virology [ 1098-5514 ] ; 2018.
Descripteurs français
- KwdFr :
- Animaux, Cellules Vero, Coronavirus (immunologie), Infections à coronavirus (), Infections à coronavirus (immunologie), Infections à coronavirus (virologie), Methyltransferases (génétique), Methyltransferases (immunologie), Modèles animaux de maladie humaine, Mutation, Méthylation, Protéines d'archée (génétique), Protéines virales non structurales (génétique), Protéines virales non structurales (immunologie), Réplication virale, Souris, Souris de lignée BALB C, Sujet immunodéprimé, Vaccins antiviraux (génétique), Vaccins antiviraux (immunologie), Vaccins atténués (génétique), Vaccins atténués (immunologie), Vieillissement (immunologie), Virus du SRAS (génétique), Virus du SRAS (immunologie).
- MESH :
- génétique : Methyltransferases, Protéines d'archée, Protéines virales non structurales, Vaccins antiviraux, Vaccins atténués, Virus du SRAS.
- immunologie : Coronavirus, Infections à coronavirus, Methyltransferases, Protéines virales non structurales, Vaccins antiviraux, Vaccins atténués, Vieillissement, Virus du SRAS.
- virologie : Infections à coronavirus.
- Animaux, Cellules Vero, Infections à coronavirus, Modèles animaux de maladie humaine, Mutation, Méthylation, Réplication virale, Souris, Souris de lignée BALB C, Sujet immunodéprimé.
English descriptors
- KwdEn :
- Aging (immunology), Animals, Archaeal Proteins (genetics), Chlorocebus aethiops, Coronavirus (immunology), Coronavirus Infections (immunology), Coronavirus Infections (prevention & control), Coronavirus Infections (virology), Disease Models, Animal, Immunocompromised Host, Methylation, Methyltransferases (genetics), Methyltransferases (immunology), Mice, Mice, Inbred BALB C, Mutation, SARS Virus (genetics), SARS Virus (immunology), Vaccines, Attenuated (genetics), Vaccines, Attenuated (immunology), Vero Cells, Viral Nonstructural Proteins (genetics), Viral Nonstructural Proteins (immunology), Viral Vaccines (genetics), Viral Vaccines (immunology), Virus Replication.
- MESH :
- chemical , genetics : Archaeal Proteins, Methyltransferases, Vaccines, Attenuated, Viral Nonstructural Proteins, Viral Vaccines.
- genetics : SARS Virus.
- immunology : Aging, Coronavirus, Coronavirus Infections, Methyltransferases, SARS Virus, Vaccines, Attenuated, Viral Nonstructural Proteins, Viral Vaccines.
- prevention & control : Coronavirus Infections.
- virology : Coronavirus Infections.
- Animals, Chlorocebus aethiops, Disease Models, Animal, Immunocompromised Host, Methylation, Mice, Mice, Inbred BALB C, Mutation, Vero Cells, Virus Replication.
Abstract
With an ongoing threat posed by circulating zoonotic strains, new strategies are required to prepare for the next emergent coronavirus (CoV). Previously, groups had targeted conserved coronavirus proteins as a strategy to generate live attenuated vaccine strains against current and future CoVs. With this in mind, we explored whether manipulation of CoV NSP16, a conserved 2'O methyltransferase (MTase), could provide a broad attenuation platform against future emergent strains. Using the severe acute respiratory syndrome-CoV mouse model, an NSP16 mutant vaccine was evaluated for protection from heterologous challenge, efficacy in the aging host, and potential for reversion to pathogenesis. Despite some success, concerns for virulence in the aged and potential for reversion makes targeting NSP16 alone an untenable approach. However, combining a 2'O MTase mutation with a previously described CoV fidelity mutant produced a vaccine strain capable of protection from heterologous virus challenge, efficacy in aged mice, and no evidence for reversion. Together, the results indicate that targeting the CoV 2'O MTase in parallel with other conserved attenuating mutations may provide a platform strategy for rapidly generating live attenuated coronavirus vaccines.IMPORTANCE Emergent coronaviruses remain a significant threat to global public health and rapid response vaccine platforms are needed to stem future outbreaks. However, failure of many previous CoV vaccine formulations has clearly highlighted the need to test efficacy under different conditions and especially in vulnerable populations such as the aged and immunocompromised. This study illustrates that despite success in young models, the 2'O methyltransferase mutant carries too much risk for pathogenesis and reversion in vulnerable models to be used as a stand-alone vaccine strategy. Importantly, the 2'O methyltransferase mutation can be paired with other attenuating approaches to provide robust protection from heterologous challenge and in vulnerable populations. Coupled with increased safety and reduced pathogenesis, the study highlights the potential for 2'O methyltransferase attenuation as a major component of future live attenuated coronavirus vaccines.
DOI: 10.1128/JVI.00710-18
PubMed: 29976657
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000845
- to stream PubMed, to step Curation: 000845
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pubmed:29976657Le document en format XML
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<front><div type="abstract" xml:lang="en">With an ongoing threat posed by circulating zoonotic strains, new strategies are required to prepare for the next emergent coronavirus (CoV). Previously, groups had targeted conserved coronavirus proteins as a strategy to generate live attenuated vaccine strains against current and future CoVs. With this in mind, we explored whether manipulation of CoV NSP16, a conserved 2'O methyltransferase (MTase), could provide a broad attenuation platform against future emergent strains. Using the severe acute respiratory syndrome-CoV mouse model, an NSP16 mutant vaccine was evaluated for protection from heterologous challenge, efficacy in the aging host, and potential for reversion to pathogenesis. Despite some success, concerns for virulence in the aged and potential for reversion makes targeting NSP16 alone an untenable approach. However, combining a 2'O MTase mutation with a previously described CoV fidelity mutant produced a vaccine strain capable of protection from heterologous virus challenge, efficacy in aged mice, and no evidence for reversion. Together, the results indicate that targeting the CoV 2'O MTase in parallel with other conserved attenuating mutations may provide a platform strategy for rapidly generating live attenuated coronavirus vaccines.<b>IMPORTANCE</b>
Emergent coronaviruses remain a significant threat to global public health and rapid response vaccine platforms are needed to stem future outbreaks. However, failure of many previous CoV vaccine formulations has clearly highlighted the need to test efficacy under different conditions and especially in vulnerable populations such as the aged and immunocompromised. This study illustrates that despite success in young models, the 2'O methyltransferase mutant carries too much risk for pathogenesis and reversion in vulnerable models to be used as a stand-alone vaccine strategy. Importantly, the 2'O methyltransferase mutation can be paired with other attenuating approaches to provide robust protection from heterologous challenge and in vulnerable populations. Coupled with increased safety and reduced pathogenesis, the study highlights the potential for 2'O methyltransferase attenuation as a major component of future live attenuated coronavirus vaccines.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">29976657</PMID>
<DateCompleted><Year>2018</Year>
<Month>08</Month>
<Day>24</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>04</Month>
<Day>15</Day>
</DateRevised>
<Article PubModel="Electronic-Print"><Journal><ISSN IssnType="Electronic">1098-5514</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>92</Volume>
<Issue>17</Issue>
<PubDate><Year>2018</Year>
<Month>09</Month>
<Day>01</Day>
</PubDate>
</JournalIssue>
<Title>Journal of virology</Title>
<ISOAbbreviation>J. Virol.</ISOAbbreviation>
</Journal>
<ArticleTitle>Combination Attenuation Offers Strategy for Live Attenuated Coronavirus Vaccines.</ArticleTitle>
<ELocationID EIdType="pii" ValidYN="Y">e00710-18</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1128/JVI.00710-18</ELocationID>
<Abstract><AbstractText>With an ongoing threat posed by circulating zoonotic strains, new strategies are required to prepare for the next emergent coronavirus (CoV). Previously, groups had targeted conserved coronavirus proteins as a strategy to generate live attenuated vaccine strains against current and future CoVs. With this in mind, we explored whether manipulation of CoV NSP16, a conserved 2'O methyltransferase (MTase), could provide a broad attenuation platform against future emergent strains. Using the severe acute respiratory syndrome-CoV mouse model, an NSP16 mutant vaccine was evaluated for protection from heterologous challenge, efficacy in the aging host, and potential for reversion to pathogenesis. Despite some success, concerns for virulence in the aged and potential for reversion makes targeting NSP16 alone an untenable approach. However, combining a 2'O MTase mutation with a previously described CoV fidelity mutant produced a vaccine strain capable of protection from heterologous virus challenge, efficacy in aged mice, and no evidence for reversion. Together, the results indicate that targeting the CoV 2'O MTase in parallel with other conserved attenuating mutations may provide a platform strategy for rapidly generating live attenuated coronavirus vaccines.<b>IMPORTANCE</b>
Emergent coronaviruses remain a significant threat to global public health and rapid response vaccine platforms are needed to stem future outbreaks. However, failure of many previous CoV vaccine formulations has clearly highlighted the need to test efficacy under different conditions and especially in vulnerable populations such as the aged and immunocompromised. This study illustrates that despite success in young models, the 2'O methyltransferase mutant carries too much risk for pathogenesis and reversion in vulnerable models to be used as a stand-alone vaccine strategy. Importantly, the 2'O methyltransferase mutation can be paired with other attenuating approaches to provide robust protection from heterologous challenge and in vulnerable populations. Coupled with increased safety and reduced pathogenesis, the study highlights the potential for 2'O methyltransferase attenuation as a major component of future live attenuated coronavirus vaccines.</AbstractText>
<CopyrightInformation>Copyright © 2018 American Society for Microbiology.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Menachery</LastName>
<ForeName>Vineet D</ForeName>
<Initials>VD</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gralinski</LastName>
<ForeName>Lisa E</ForeName>
<Initials>LE</Initials>
<AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mitchell</LastName>
<ForeName>Hugh D</ForeName>
<Initials>HD</Initials>
<AffiliationInfo><Affiliation>Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Dinnon</LastName>
<ForeName>Kenneth H</ForeName>
<Initials>KH</Initials>
<Suffix>3rd</Suffix>
<AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Leist</LastName>
<ForeName>Sarah R</ForeName>
<Initials>SR</Initials>
<AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yount</LastName>
<ForeName>Boyd L</ForeName>
<Initials>BL</Initials>
<Suffix>Jr</Suffix>
<AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>McAnarney</LastName>
<ForeName>Eileen T</ForeName>
<Initials>ET</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Graham</LastName>
<ForeName>Rachel L</ForeName>
<Initials>RL</Initials>
<AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Waters</LastName>
<ForeName>Katrina M</ForeName>
<Initials>KM</Initials>
<AffiliationInfo><Affiliation>Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Baric</LastName>
<ForeName>Ralph S</ForeName>
<Initials>RS</Initials>
<AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA Rbaric@email.unc.edu.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>R00 AG049092</GrantID>
<Acronym>AG</Acronym>
<Agency>NIA NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 AI108197</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>K99 AG049092</GrantID>
<Acronym>AG</Acronym>
<Agency>NIA NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>U19 AI106772</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>U19 AI100625</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType>
<PublicationType UI="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2018</Year>
<Month>08</Month>
<Day>16</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>J Virol</MedlineTA>
<NlmUniqueID>0113724</NlmUniqueID>
<ISSNLinking>0022-538X</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D019843">Archaeal Proteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014613">Vaccines, Attenuated</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D017361">Viral Nonstructural Proteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014765">Viral Vaccines</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.1.1.-</RegistryNumber>
<NameOfSubstance UI="D008780">Methyltransferases</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.1.1.-</RegistryNumber>
<NameOfSubstance UI="C558879">Nsp16 protein, SARS virus</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.1.1.-</RegistryNumber>
<NameOfSubstance UI="C023894">methylcobalamin-coenzyme M methyltransferase</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000375" MajorTopicYN="N">Aging</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D019843" MajorTopicYN="N">Archaeal Proteins</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002522" MajorTopicYN="N">Chlorocebus aethiops</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D017934" MajorTopicYN="N">Coronavirus</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016867" MajorTopicYN="N">Immunocompromised Host</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008745" MajorTopicYN="N">Methylation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008780" MajorTopicYN="N">Methyltransferases</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008807" MajorTopicYN="N">Mice, Inbred BALB C</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009154" MajorTopicYN="N">Mutation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D045473" MajorTopicYN="N">SARS Virus</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014613" MajorTopicYN="N">Vaccines, Attenuated</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014709" MajorTopicYN="N">Vero Cells</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D017361" MajorTopicYN="N">Viral Nonstructural Proteins</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014765" MajorTopicYN="N">Viral Vaccines</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014779" MajorTopicYN="N">Virus Replication</DescriptorName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">MERS-CoV</Keyword>
<Keyword MajorTopicYN="Y">SARS-CoV</Keyword>
<Keyword MajorTopicYN="Y">aged</Keyword>
<Keyword MajorTopicYN="Y">coronavirus</Keyword>
<Keyword MajorTopicYN="Y">live attenuated</Keyword>
<Keyword MajorTopicYN="Y">vaccine</Keyword>
</KeywordList>
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<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year>
<Month>04</Month>
<Day>26</Day>
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<Month>06</Month>
<Day>20</Day>
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<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Caroline du Nord</li>
<li>Texas</li>
<li>Washington (État)</li>
</region>
<settlement><li>Chapel Hill (Caroline du Nord)</li>
</settlement>
<orgName><li>Université de Caroline du Nord à Chapel Hill</li>
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<tree><country name="États-Unis"><region name="Texas"><name sortKey="Menachery, Vineet D" sort="Menachery, Vineet D" uniqKey="Menachery V" first="Vineet D" last="Menachery">Vineet D. Menachery</name>
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<name sortKey="Graham, Rachel L" sort="Graham, Rachel L" uniqKey="Graham R" first="Rachel L" last="Graham">Rachel L. Graham</name>
<name sortKey="Gralinski, Lisa E" sort="Gralinski, Lisa E" uniqKey="Gralinski L" first="Lisa E" last="Gralinski">Lisa E. Gralinski</name>
<name sortKey="Leist, Sarah R" sort="Leist, Sarah R" uniqKey="Leist S" first="Sarah R" last="Leist">Sarah R. Leist</name>
<name sortKey="Mcanarney, Eileen T" sort="Mcanarney, Eileen T" uniqKey="Mcanarney E" first="Eileen T" last="Mcanarney">Eileen T. Mcanarney</name>
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