Serveur d'exploration MERS

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ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice.

Identifieur interne : 000C73 ( PubMed/Curation ); précédent : 000C72; suivant : 000C74

ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice.

Auteurs : Naif Khalaf Alharbi [Arabie saoudite] ; Eriko Padron-Regalado [Royaume-Uni] ; Craig P. Thompson [Royaume-Uni] ; Alexandra Kupke [Allemagne] ; Daniel Wells [Royaume-Uni] ; Megan A. Sloan [Royaume-Uni] ; Keith Grehan [Royaume-Uni] ; Nigel Temperton [Royaume-Uni] ; Teresa Lambe [Royaume-Uni] ; George Warimwe [Royaume-Uni] ; Stephan Becker [Allemagne] ; Adrian V S. Hill [Royaume-Uni] ; Sarah C. Gilbert [Royaume-Uni]

Source :

RBID : pubmed:28579232

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English descriptors

Abstract

The Middle East respiratory syndrome coronavirus (MERS-CoV) has infected more than 1900 humans, since 2012. The syndrome ranges from asymptomatic and mild cases to severe pneumonia and death. The virus is believed to be circulating in dromedary camels without notable symptoms since the 1980s. Therefore, dromedary camels are considered the only animal source of infection. Neither antiviral drugs nor vaccines are approved for veterinary or medical use despite active research on this area. Here, we developed four vaccine candidates against MERS-CoV based on ChAdOx1 and MVA viral vectors, two candidates per vector. All vaccines contained the full-length spike gene of MERS-CoV; ChAdOx1 MERS vaccines were produced with or without the leader sequence of the human tissue plasminogen activator gene (tPA) where MVA MERS vaccines were produced with tPA, but either the mH5 or F11 promoter driving expression of the spike gene. All vaccine candidates were evaluated in a mouse model in prime only or prime-boost regimens. ChAdOx1 MERS with tPA induced higher neutralising antibodies than ChAdOx1 MERS without tPA. A single dose of ChAdOx1 MERS with tPA elicited cellular immune responses as well as neutralising antibodies that were boosted to a significantly higher level by MVA MERS. The humoral immunogenicity of a single dose of ChAdOx1 MERS with tPA was equivalent to two doses of MVA MERS (also with tPA). MVA MERS with mH5 or F11 promoter induced similar antibody levels; however, F11 promoter enhanced the cellular immunogenicity of MVA MERS to significantly higher magnitudes. In conclusion, our study showed that MERS-CoV vaccine candidates could be optimized by utilising different viral vectors, various genetic designs of the vectors, or different regimens to increase immunogenicity. ChAdOx1 and MVA vectored vaccines have been safely evaluated in camels and humans and these MERS vaccine candidates should now be tested in camels and in clinical trials.

DOI: 10.1016/j.vaccine.2017.05.032
PubMed: 28579232

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Le document en format XML

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<name sortKey="Becker, Stephan" sort="Becker, Stephan" uniqKey="Becker S" first="Stephan" last="Becker">Stephan Becker</name>
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<term>Antibodies, Neutralizing (immunology)</term>
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<front>
<div type="abstract" xml:lang="en">The Middle East respiratory syndrome coronavirus (MERS-CoV) has infected more than 1900 humans, since 2012. The syndrome ranges from asymptomatic and mild cases to severe pneumonia and death. The virus is believed to be circulating in dromedary camels without notable symptoms since the 1980s. Therefore, dromedary camels are considered the only animal source of infection. Neither antiviral drugs nor vaccines are approved for veterinary or medical use despite active research on this area. Here, we developed four vaccine candidates against MERS-CoV based on ChAdOx1 and MVA viral vectors, two candidates per vector. All vaccines contained the full-length spike gene of MERS-CoV; ChAdOx1 MERS vaccines were produced with or without the leader sequence of the human tissue plasminogen activator gene (tPA) where MVA MERS vaccines were produced with tPA, but either the mH5 or F11 promoter driving expression of the spike gene. All vaccine candidates were evaluated in a mouse model in prime only or prime-boost regimens. ChAdOx1 MERS with tPA induced higher neutralising antibodies than ChAdOx1 MERS without tPA. A single dose of ChAdOx1 MERS with tPA elicited cellular immune responses as well as neutralising antibodies that were boosted to a significantly higher level by MVA MERS. The humoral immunogenicity of a single dose of ChAdOx1 MERS with tPA was equivalent to two doses of MVA MERS (also with tPA). MVA MERS with mH5 or F11 promoter induced similar antibody levels; however, F11 promoter enhanced the cellular immunogenicity of MVA MERS to significantly higher magnitudes. In conclusion, our study showed that MERS-CoV vaccine candidates could be optimized by utilising different viral vectors, various genetic designs of the vectors, or different regimens to increase immunogenicity. ChAdOx1 and MVA vectored vaccines have been safely evaluated in camels and humans and these MERS vaccine candidates should now be tested in camels and in clinical trials.</div>
</front>
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<Day>02</Day>
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<ISSN IssnType="Electronic">1873-2518</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>35</Volume>
<Issue>30</Issue>
<PubDate>
<Year>2017</Year>
<Month>06</Month>
<Day>27</Day>
</PubDate>
</JournalIssue>
<Title>Vaccine</Title>
<ISOAbbreviation>Vaccine</ISOAbbreviation>
</Journal>
<ArticleTitle>ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice.</ArticleTitle>
<Pagination>
<MedlinePgn>3780-3788</MedlinePgn>
</Pagination>
<ELocationID EIdType="pii" ValidYN="Y">S0264-410X(17)30656-4</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.vaccine.2017.05.032</ELocationID>
<Abstract>
<AbstractText>The Middle East respiratory syndrome coronavirus (MERS-CoV) has infected more than 1900 humans, since 2012. The syndrome ranges from asymptomatic and mild cases to severe pneumonia and death. The virus is believed to be circulating in dromedary camels without notable symptoms since the 1980s. Therefore, dromedary camels are considered the only animal source of infection. Neither antiviral drugs nor vaccines are approved for veterinary or medical use despite active research on this area. Here, we developed four vaccine candidates against MERS-CoV based on ChAdOx1 and MVA viral vectors, two candidates per vector. All vaccines contained the full-length spike gene of MERS-CoV; ChAdOx1 MERS vaccines were produced with or without the leader sequence of the human tissue plasminogen activator gene (tPA) where MVA MERS vaccines were produced with tPA, but either the mH5 or F11 promoter driving expression of the spike gene. All vaccine candidates were evaluated in a mouse model in prime only or prime-boost regimens. ChAdOx1 MERS with tPA induced higher neutralising antibodies than ChAdOx1 MERS without tPA. A single dose of ChAdOx1 MERS with tPA elicited cellular immune responses as well as neutralising antibodies that were boosted to a significantly higher level by MVA MERS. The humoral immunogenicity of a single dose of ChAdOx1 MERS with tPA was equivalent to two doses of MVA MERS (also with tPA). MVA MERS with mH5 or F11 promoter induced similar antibody levels; however, F11 promoter enhanced the cellular immunogenicity of MVA MERS to significantly higher magnitudes. In conclusion, our study showed that MERS-CoV vaccine candidates could be optimized by utilising different viral vectors, various genetic designs of the vectors, or different regimens to increase immunogenicity. ChAdOx1 and MVA vectored vaccines have been safely evaluated in camels and humans and these MERS vaccine candidates should now be tested in camels and in clinical trials.</AbstractText>
<CopyrightInformation>Copyright © 2017. Published by Elsevier Ltd.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y">
<LastName>Alharbi</LastName>
<ForeName>Naif Khalaf</ForeName>
<Initials>NK</Initials>
<AffiliationInfo>
<Affiliation>The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK; King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Electronic address: harbina2@ngha.med.sa.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Padron-Regalado</LastName>
<ForeName>Eriko</ForeName>
<Initials>E</Initials>
<AffiliationInfo>
<Affiliation>The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Thompson</LastName>
<ForeName>Craig P</ForeName>
<Initials>CP</Initials>
<AffiliationInfo>
<Affiliation>The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK; Department of Zoology, University of Oxford, Oxford, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Kupke</LastName>
<ForeName>Alexandra</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>Institute of Virology, Philipps University of Marburg, Marburg, Germany; German Center for Infection Research, TTU Emerging Infections, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Wells</LastName>
<ForeName>Daniel</ForeName>
<Initials>D</Initials>
<AffiliationInfo>
<Affiliation>The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Sloan</LastName>
<ForeName>Megan A</ForeName>
<Initials>MA</Initials>
<AffiliationInfo>
<Affiliation>The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Grehan</LastName>
<ForeName>Keith</ForeName>
<Initials>K</Initials>
<AffiliationInfo>
<Affiliation>Viral Pseudotype Unit, School of Pharmacy, University of Kent, Chatham Maritime, Kent ME4 4TB, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Temperton</LastName>
<ForeName>Nigel</ForeName>
<Initials>N</Initials>
<AffiliationInfo>
<Affiliation>Viral Pseudotype Unit, School of Pharmacy, University of Kent, Chatham Maritime, Kent ME4 4TB, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Lambe</LastName>
<ForeName>Teresa</ForeName>
<Initials>T</Initials>
<AffiliationInfo>
<Affiliation>The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Warimwe</LastName>
<ForeName>George</ForeName>
<Initials>G</Initials>
<AffiliationInfo>
<Affiliation>The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Becker</LastName>
<ForeName>Stephan</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>Institute of Virology, Philipps University of Marburg, Marburg, Germany; German Center for Infection Research, TTU Emerging Infections, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Hill</LastName>
<ForeName>Adrian V S</ForeName>
<Initials>AVS</Initials>
<AffiliationInfo>
<Affiliation>The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Gilbert</LastName>
<ForeName>Sarah C</ForeName>
<Initials>SC</Initials>
<AffiliationInfo>
<Affiliation>The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y">
<Grant>
<GrantID>MC_PC_14111</GrantID>
<Agency>Medical Research Council</Agency>
<Country>United Kingdom</Country>
</Grant>
</GrantList>
<PublicationTypeList>
<PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic">
<Year>2017</Year>
<Month>06</Month>
<Day>01</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo>
<Country>Netherlands</Country>
<MedlineTA>Vaccine</MedlineTA>
<NlmUniqueID>8406899</NlmUniqueID>
<ISSNLinking>0264-410X</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D057134">Antibodies, Neutralizing</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000914">Antibodies, Viral</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C560489">MVA vaccine</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D064370">Spike Glycoprotein, Coronavirus</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014614">Vaccines, Synthetic</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014765">Viral Vaccines</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList>
<MeshHeading>
<DescriptorName UI="D000256" MajorTopicYN="N">Adenoviridae</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D057134" MajorTopicYN="N">Antibodies, Neutralizing</DescriptorName>
<QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000914" MajorTopicYN="N">Antibodies, Viral</DescriptorName>
<QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">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>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D004306" MajorTopicYN="N">Dose-Response Relationship, Immunologic</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D007111" MajorTopicYN="Y">Immunity, Cellular</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D056724" MajorTopicYN="N">Immunity, Humoral</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000071497" MajorTopicYN="N">Immunogenicity, Vaccine</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D065207" MajorTopicYN="N">Middle East Respiratory Syndrome Coronavirus</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D064370" MajorTopicYN="N">Spike Glycoprotein, Coronavirus</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D014611" MajorTopicYN="N">Vaccination</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D014614" MajorTopicYN="N">Vaccines, Synthetic</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D014765" MajorTopicYN="N">Viral Vaccines</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM">
<Keyword MajorTopicYN="Y">Adenoviral vector</Keyword>
<Keyword MajorTopicYN="Y">ChAdOx1</Keyword>
<Keyword MajorTopicYN="Y">Coronavirus</Keyword>
<Keyword MajorTopicYN="Y">Immunogenicity</Keyword>
<Keyword MajorTopicYN="Y">MERS-CoV</Keyword>
<Keyword MajorTopicYN="Y">MVA</Keyword>
<Keyword MajorTopicYN="Y">Poxviral vector</Keyword>
<Keyword MajorTopicYN="Y">Prime boost</Keyword>
<Keyword MajorTopicYN="Y">Vaccination</Keyword>
<Keyword MajorTopicYN="Y">Vaccine</Keyword>
</KeywordList>
</MedlineCitation>
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<Year>2017</Year>
<Month>03</Month>
<Day>02</Day>
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<PubMedPubDate PubStatus="revised">
<Year>2017</Year>
<Month>04</Month>
<Day>30</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted">
<Year>2017</Year>
<Month>05</Month>
<Day>10</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed">
<Year>2017</Year>
<Month>6</Month>
<Day>6</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline">
<Year>2018</Year>
<Month>3</Month>
<Day>3</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez">
<Year>2017</Year>
<Month>6</Month>
<Day>6</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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</History>
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