ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice
Identifieur interne : 000914 ( Pmc/Checkpoint ); précédent : 000913; suivant : 000915ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice
Auteurs : Naif Khalaf Alharbi [Royaume-Uni, 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 :
- Vaccine [ 0264-410X ] ; 2017.
Abstract
Inserting tPA leader sequence enhanced humoral responses of ChAdOx1 MERS. ChAdOx1 MERS elicited cellular immunity and neutralising antibodies. ChAdOx1 MERS responses were boosted by MVA MERS. Immunogenicity of a single dose of ChAdOx1 MERS was equivalent to 2 doses of MVA MERS. In MVA, F11 promoter enhanced cellular, but not humoral, immunogenicity, comparing to mH5 promoter.
Url:
DOI: 10.1016/j.vaccine.2017.05.032
PubMed: 28579232
PubMed Central: 5516308
Affiliations:
- Allemagne, Arabie saoudite, Royaume-Uni
- Angleterre, District de Giessen, Hesse (Land), Oxfordshire
- Marbourg, Oxford
- Université d'Oxford
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Thompson</name><affiliation wicri:level="4"><nlm:aff id="af005">The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Jenner Institute, University of Oxford, Oxford OX3 7DQ</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="af015">Department of Zoology, University of Oxford, Oxford, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Zoology, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Kupke, Alexandra" sort="Kupke, Alexandra" uniqKey="Kupke A" first="Alexandra" last="Kupke">Alexandra Kupke</name><affiliation wicri:level="3"><nlm:aff id="af020">Institute of Virology, Philipps University of Marburg, Marburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Philipps University of Marburg, Marburg</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Giessen</region><settlement type="city">Marbourg</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="af025">German Center for Infection Research, TTU Emerging Infections, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>German Center for Infection Research, TTU Emerging Infections</wicri:regionArea><wicri:noRegion>TTU Emerging Infections</wicri:noRegion><wicri:noRegion>TTU Emerging Infections</wicri:noRegion><wicri:noRegion>TTU Emerging Infections</wicri:noRegion></affiliation></author><author><name sortKey="Wells, Daniel" sort="Wells, Daniel" uniqKey="Wells D" first="Daniel" last="Wells">Daniel Wells</name><affiliation wicri:level="4"><nlm:aff id="af005">The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Jenner Institute, University of Oxford, Oxford OX3 7DQ</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Sloan, Megan A" sort="Sloan, Megan A" uniqKey="Sloan M" first="Megan A." last="Sloan">Megan A. Sloan</name><affiliation wicri:level="4"><nlm:aff id="af005">The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Jenner Institute, University of Oxford, Oxford OX3 7DQ</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Grehan, Keith" sort="Grehan, Keith" uniqKey="Grehan K" first="Keith" last="Grehan">Keith Grehan</name><affiliation wicri:level="1"><nlm:aff id="af030">Viral Pseudotype Unit, School of Pharmacy, University of Kent, Chatham Maritime, Kent ME4 4TB, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Viral Pseudotype Unit, School of Pharmacy, University of Kent, Chatham Maritime, Kent ME4 4TB</wicri:regionArea><wicri:noRegion>Kent ME4 4TB</wicri:noRegion></affiliation></author><author><name sortKey="Temperton, Nigel" sort="Temperton, Nigel" uniqKey="Temperton N" first="Nigel" last="Temperton">Nigel Temperton</name><affiliation wicri:level="1"><nlm:aff id="af030">Viral Pseudotype Unit, School of Pharmacy, University of Kent, Chatham Maritime, Kent ME4 4TB, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Viral Pseudotype Unit, School of Pharmacy, University of Kent, Chatham Maritime, Kent ME4 4TB</wicri:regionArea><wicri:noRegion>Kent ME4 4TB</wicri:noRegion></affiliation></author><author><name sortKey="Lambe, Teresa" sort="Lambe, Teresa" uniqKey="Lambe T" first="Teresa" last="Lambe">Teresa Lambe</name><affiliation wicri:level="4"><nlm:aff id="af005">The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Jenner Institute, University of Oxford, Oxford OX3 7DQ</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Warimwe, George" sort="Warimwe, George" uniqKey="Warimwe G" first="George" last="Warimwe">George Warimwe</name><affiliation wicri:level="4"><nlm:aff id="af005">The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Jenner Institute, University of Oxford, Oxford OX3 7DQ</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Becker, Stephan" sort="Becker, Stephan" uniqKey="Becker S" first="Stephan" last="Becker">Stephan Becker</name><affiliation wicri:level="3"><nlm:aff id="af020">Institute of Virology, Philipps University of Marburg, Marburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Philipps University of Marburg, Marburg</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Giessen</region><settlement type="city">Marbourg</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="af025">German Center for Infection Research, TTU Emerging Infections, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>German Center for Infection Research, TTU Emerging Infections</wicri:regionArea><wicri:noRegion>TTU Emerging Infections</wicri:noRegion><wicri:noRegion>TTU Emerging Infections</wicri:noRegion><wicri:noRegion>TTU Emerging Infections</wicri:noRegion></affiliation></author><author><name sortKey="Hill, Adrian V S" sort="Hill, Adrian V S" uniqKey="Hill A" first="Adrian V. 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Thompson</name><affiliation wicri:level="4"><nlm:aff id="af005">The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Jenner Institute, University of Oxford, Oxford OX3 7DQ</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="af015">Department of Zoology, University of Oxford, Oxford, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Zoology, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Kupke, Alexandra" sort="Kupke, Alexandra" uniqKey="Kupke A" first="Alexandra" last="Kupke">Alexandra Kupke</name><affiliation wicri:level="3"><nlm:aff id="af020">Institute of Virology, Philipps University of Marburg, Marburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Philipps University of Marburg, Marburg</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Giessen</region><settlement type="city">Marbourg</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="af025">German Center for Infection Research, TTU Emerging Infections, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>German Center for Infection Research, TTU Emerging Infections</wicri:regionArea><wicri:noRegion>TTU Emerging Infections</wicri:noRegion><wicri:noRegion>TTU Emerging Infections</wicri:noRegion><wicri:noRegion>TTU Emerging Infections</wicri:noRegion></affiliation></author><author><name sortKey="Wells, Daniel" sort="Wells, Daniel" uniqKey="Wells D" first="Daniel" last="Wells">Daniel Wells</name><affiliation wicri:level="4"><nlm:aff id="af005">The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Jenner Institute, University of Oxford, Oxford OX3 7DQ</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Sloan, Megan A" sort="Sloan, Megan A" uniqKey="Sloan M" first="Megan A." last="Sloan">Megan A. Sloan</name><affiliation wicri:level="4"><nlm:aff id="af005">The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Jenner Institute, University of Oxford, Oxford OX3 7DQ</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Grehan, Keith" sort="Grehan, Keith" uniqKey="Grehan K" first="Keith" last="Grehan">Keith Grehan</name><affiliation wicri:level="1"><nlm:aff id="af030">Viral Pseudotype Unit, School of Pharmacy, University of Kent, Chatham Maritime, Kent ME4 4TB, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Viral Pseudotype Unit, School of Pharmacy, University of Kent, Chatham Maritime, Kent ME4 4TB</wicri:regionArea><wicri:noRegion>Kent ME4 4TB</wicri:noRegion></affiliation></author><author><name sortKey="Temperton, Nigel" sort="Temperton, Nigel" uniqKey="Temperton N" first="Nigel" last="Temperton">Nigel Temperton</name><affiliation wicri:level="1"><nlm:aff id="af030">Viral Pseudotype Unit, School of Pharmacy, University of Kent, Chatham Maritime, Kent ME4 4TB, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Viral Pseudotype Unit, School of Pharmacy, University of Kent, Chatham Maritime, Kent ME4 4TB</wicri:regionArea><wicri:noRegion>Kent ME4 4TB</wicri:noRegion></affiliation></author><author><name sortKey="Lambe, Teresa" sort="Lambe, Teresa" uniqKey="Lambe T" first="Teresa" last="Lambe">Teresa Lambe</name><affiliation wicri:level="4"><nlm:aff id="af005">The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Jenner Institute, University of Oxford, Oxford OX3 7DQ</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Warimwe, George" sort="Warimwe, George" uniqKey="Warimwe G" first="George" last="Warimwe">George Warimwe</name><affiliation wicri:level="4"><nlm:aff id="af005">The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Jenner Institute, University of Oxford, Oxford OX3 7DQ</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Becker, Stephan" sort="Becker, Stephan" uniqKey="Becker S" first="Stephan" last="Becker">Stephan Becker</name><affiliation wicri:level="3"><nlm:aff id="af020">Institute of Virology, Philipps University of Marburg, Marburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Philipps University of Marburg, Marburg</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Giessen</region><settlement type="city">Marbourg</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="af025">German Center for Infection Research, TTU Emerging Infections, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>German Center for Infection Research, TTU Emerging Infections</wicri:regionArea><wicri:noRegion>TTU Emerging Infections</wicri:noRegion><wicri:noRegion>TTU Emerging Infections</wicri:noRegion><wicri:noRegion>TTU Emerging Infections</wicri:noRegion></affiliation></author><author><name sortKey="Hill, Adrian V S" sort="Hill, Adrian V S" uniqKey="Hill A" first="Adrian V. S." last="Hill">Adrian V. S. Hill</name><affiliation wicri:level="4"><nlm:aff id="af005">The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Jenner Institute, University of Oxford, Oxford OX3 7DQ</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Gilbert, Sarah C" sort="Gilbert, Sarah C" uniqKey="Gilbert S" first="Sarah C." last="Gilbert">Sarah C. Gilbert</name><affiliation wicri:level="4"><nlm:aff id="af005">The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Jenner Institute, University of Oxford, Oxford OX3 7DQ</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author></analytic><series><title level="j">Vaccine</title><idno type="ISSN">0264-410X</idno><idno type="eISSN">1873-2518</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Highlights</title><p><list list-type="simple" id="l0005"><list-item id="o0005"><label>•</label><p id="p0005">Inserting tPA leader sequence enhanced humoral responses of ChAdOx1 MERS.</p></list-item><list-item id="o0010"><label>•</label><p id="p0010">ChAdOx1 MERS elicited cellular immunity and neutralising antibodies.</p></list-item><list-item id="o0015"><label>•</label><p id="p0015">ChAdOx1 MERS responses were boosted by MVA MERS.</p></list-item><list-item id="o0020"><label>•</label><p id="p0020">Immunogenicity of a single dose of ChAdOx1 MERS was equivalent to 2 doses of MVA MERS.</p></list-item><list-item id="o0025"><label>•</label><p id="p0025">In MVA, F11 promoter enhanced cellular, but not humoral, immunogenicity, comparing to mH5 promoter.</p></list-item></list></p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zaki, A M" uniqKey="Zaki A">A.M. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Vaccine</journal-id><journal-id journal-id-type="iso-abbrev">Vaccine</journal-id><journal-title-group><journal-title>Vaccine</journal-title></journal-title-group><issn pub-type="ppub">0264-410X</issn><issn pub-type="epub">1873-2518</issn><publisher><publisher-name>The Authors. Published by Elsevier Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28579232</article-id><article-id pub-id-type="pmc">5516308</article-id><article-id pub-id-type="publisher-id">S0264-410X(17)30656-4</article-id><article-id pub-id-type="doi">10.1016/j.vaccine.2017.05.032</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice</article-title></title-group><contrib-group><contrib contrib-type="author" id="au005"><name><surname>Alharbi</surname><given-names>Naif Khalaf</given-names></name><email>harbina2@ngha.med.sa</email><xref rid="af005" ref-type="aff">a</xref><xref rid="af010" ref-type="aff">b</xref><xref rid="cor1" ref-type="corresp">⁎</xref></contrib><contrib contrib-type="author" id="au010"><name><surname>Padron-Regalado</surname><given-names>Eriko</given-names></name><xref rid="af005" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au015"><name><surname>Thompson</surname><given-names>Craig P.</given-names></name><xref rid="af005" ref-type="aff">a</xref><xref rid="af015" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au020"><name><surname>Kupke</surname><given-names>Alexandra</given-names></name><xref rid="af020" ref-type="aff">d</xref><xref rid="af025" ref-type="aff">e</xref></contrib><contrib contrib-type="author" id="au025"><name><surname>Wells</surname><given-names>Daniel</given-names></name><xref rid="af005" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au030"><name><surname>Sloan</surname><given-names>Megan A.</given-names></name><xref rid="af005" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au035"><name><surname>Grehan</surname><given-names>Keith</given-names></name><xref rid="af030" ref-type="aff">f</xref></contrib><contrib contrib-type="author" id="au040"><name><surname>Temperton</surname><given-names>Nigel</given-names></name><xref rid="af030" ref-type="aff">f</xref></contrib><contrib contrib-type="author" id="au045"><name><surname>Lambe</surname><given-names>Teresa</given-names></name><xref rid="af005" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au050"><name><surname>Warimwe</surname><given-names>George</given-names></name><xref rid="af005" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au055"><name><surname>Becker</surname><given-names>Stephan</given-names></name><xref rid="af020" ref-type="aff">d</xref><xref rid="af025" ref-type="aff">e</xref></contrib><contrib contrib-type="author" id="au060"><name><surname>Hill</surname><given-names>Adrian V.S.</given-names></name><xref rid="af005" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au065"><name><surname>Gilbert</surname><given-names>Sarah C.</given-names></name><xref rid="af005" ref-type="aff">a</xref></contrib></contrib-group><aff id="af005"><label>a</label>The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK</aff><aff id="af010"><label>b</label>King Abdullah International Medical Research Center, Riyadh, Saudi Arabia</aff><aff id="af015"><label>c</label>Department of Zoology, University of Oxford, Oxford, UK</aff><aff id="af020"><label>d</label>Institute of Virology, Philipps University of Marburg, Marburg, Germany</aff><aff id="af025"><label>e</label>German Center for Infection Research, TTU Emerging Infections, Germany</aff><aff id="af030"><label>f</label>Viral Pseudotype Unit, School of Pharmacy, University of Kent, Chatham Maritime, Kent ME4 4TB, UK</aff><author-notes><corresp id="cor1"><label>⁎</label>Corresponding author at: King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. <email>harbina2@ngha.med.sa</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>1</day><month>6</month><year>2017</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><day>27</day><month>6</month><year>2017</year></pub-date><pub-date pub-type="epub"><day>1</day><month>6</month><year>2017</year></pub-date><volume>35</volume><issue>30</issue><fpage>3780</fpage><lpage>3788</lpage><history><date date-type="received"><day>2</day><month>3</month><year>2017</year></date><date date-type="rev-recd"><day>30</day><month>4</month><year>2017</year></date><date date-type="accepted"><day>10</day><month>5</month><year>2017</year></date></history><permissions><copyright-statement>© 2017 The Authors</copyright-statement><copyright-year>2017</copyright-year><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions><abstract abstract-type="author-highlights" id="ab005"><title>Highlights</title><p><list list-type="simple" id="l0005"><list-item id="o0005"><label>•</label><p id="p0005">Inserting tPA leader sequence enhanced humoral responses of ChAdOx1 MERS.</p></list-item><list-item id="o0010"><label>•</label><p id="p0010">ChAdOx1 MERS elicited cellular immunity and neutralising antibodies.</p></list-item><list-item id="o0015"><label>•</label><p id="p0015">ChAdOx1 MERS responses were boosted by MVA MERS.</p></list-item><list-item id="o0020"><label>•</label><p id="p0020">Immunogenicity of a single dose of ChAdOx1 MERS was equivalent to 2 doses of MVA MERS.</p></list-item><list-item id="o0025"><label>•</label><p id="p0025">In MVA, F11 promoter enhanced cellular, but not humoral, immunogenicity, comparing to mH5 promoter.</p></list-item></list></p></abstract><abstract id="ab010"><p>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.</p></abstract><kwd-group id="kg005"><title>Keywords</title><kwd>Coronavirus</kwd><kwd>MERS-CoV</kwd><kwd>ChAdOx1</kwd><kwd>Adenoviral vector</kwd><kwd>MVA</kwd><kwd>Poxviral vector</kwd><kwd>Vaccine</kwd><kwd>Prime boost</kwd><kwd>Vaccination</kwd><kwd>Immunogenicity</kwd></kwd-group></article-meta></front></pmc><affiliations><list><country><li>Allemagne</li><li>Arabie saoudite</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>District de Giessen</li><li>Hesse (Land)</li><li>Oxfordshire</li></region><settlement><li>Marbourg</li><li>Oxford</li></settlement><orgName><li>Université d'Oxford</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Alharbi, Naif Khalaf" sort="Alharbi, Naif Khalaf" uniqKey="Alharbi N" first="Naif Khalaf" last="Alharbi">Naif Khalaf Alharbi</name></region><name sortKey="Gilbert, Sarah C" sort="Gilbert, Sarah C" uniqKey="Gilbert S" first="Sarah C." last="Gilbert">Sarah C. Gilbert</name><name sortKey="Grehan, Keith" sort="Grehan, Keith" uniqKey="Grehan K" first="Keith" last="Grehan">Keith Grehan</name><name sortKey="Hill, Adrian V S" sort="Hill, Adrian V S" uniqKey="Hill A" first="Adrian V. S." last="Hill">Adrian V. S. Hill</name><name sortKey="Lambe, Teresa" sort="Lambe, Teresa" uniqKey="Lambe T" first="Teresa" last="Lambe">Teresa Lambe</name><name sortKey="Padron Regalado, Eriko" sort="Padron Regalado, Eriko" uniqKey="Padron Regalado E" first="Eriko" last="Padron-Regalado">Eriko Padron-Regalado</name><name sortKey="Sloan, Megan A" sort="Sloan, Megan A" uniqKey="Sloan M" first="Megan A." last="Sloan">Megan A. Sloan</name><name sortKey="Temperton, Nigel" sort="Temperton, Nigel" uniqKey="Temperton N" first="Nigel" last="Temperton">Nigel Temperton</name><name sortKey="Thompson, Craig P" sort="Thompson, Craig P" uniqKey="Thompson C" first="Craig P." last="Thompson">Craig P. Thompson</name><name sortKey="Thompson, Craig P" sort="Thompson, Craig P" uniqKey="Thompson C" first="Craig P." last="Thompson">Craig P. Thompson</name><name sortKey="Warimwe, George" sort="Warimwe, George" uniqKey="Warimwe G" first="George" last="Warimwe">George Warimwe</name><name sortKey="Wells, Daniel" sort="Wells, Daniel" uniqKey="Wells D" first="Daniel" last="Wells">Daniel Wells</name></country><country name="Arabie saoudite"><noRegion><name sortKey="Alharbi, Naif Khalaf" sort="Alharbi, Naif Khalaf" uniqKey="Alharbi N" first="Naif Khalaf" last="Alharbi">Naif Khalaf Alharbi</name></noRegion></country><country name="Allemagne"><region name="Hesse (Land)"><name sortKey="Kupke, Alexandra" sort="Kupke, Alexandra" uniqKey="Kupke A" first="Alexandra" last="Kupke">Alexandra Kupke</name></region><name sortKey="Becker, Stephan" sort="Becker, Stephan" uniqKey="Becker S" first="Stephan" last="Becker">Stephan Becker</name><name sortKey="Becker, Stephan" sort="Becker, Stephan" uniqKey="Becker S" first="Stephan" last="Becker">Stephan Becker</name><name sortKey="Kupke, Alexandra" sort="Kupke, Alexandra" uniqKey="Kupke A" first="Alexandra" last="Kupke">Alexandra Kupke</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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