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Serveur d'exploration MERS

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A Highly Immunogenic and Protective Middle East Respiratory Syndrome Coronavirus Vaccine Based on a Recombinant Measles Virus Vaccine Platform.

Identifieur interne : 001263 ( Ncbi/Merge ); précédent : 001262; suivant : 001264

A Highly Immunogenic and Protective Middle East Respiratory Syndrome Coronavirus Vaccine Based on a Recombinant Measles Virus Vaccine Platform.

Auteurs : Anna H. Malczyk [Allemagne] ; Alexandra Kupke [Allemagne] ; Steffen Prüfer [Allemagne] ; Vivian A. Scheuplein [Allemagne] ; Stefan Hutzler [Allemagne] ; Dorothea Kreuz [Allemagne] ; Tim Beissert [Allemagne] ; Stefanie Bauer [Allemagne] ; Stefanie Hubich-Rau [Allemagne] ; Christiane Tondera [Allemagne] ; Hosam Shams Eldin [Allemagne] ; Jörg Schmidt [Allemagne] ; Júlia Vergara-Alert [Allemagne] ; Yasemin Süzer [Allemagne] ; Janna Seifried [Allemagne] ; Kay-Martin Hanschmann [Allemagne] ; Ulrich Kalinke [Allemagne] ; Susanne Herold [Allemagne] ; Ugur Sahin [Allemagne] ; Klaus Cichutek [Allemagne] ; Zoe Waibler [Allemagne] ; Markus Eickmann [Allemagne] ; Stephan Becker [Allemagne] ; Michael D. Mühlebach [Allemagne]

Source :

RBID : pubmed:26355094

Descripteurs français

English descriptors

Abstract

In 2012, the first cases of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) were identified. Since then, more than 1,000 cases of MERS-CoV infection have been confirmed; infection is typically associated with considerable morbidity and, in approximately 30% of cases, mortality. Currently, there is no protective vaccine available. Replication-competent recombinant measles virus (MV) expressing foreign antigens constitutes a promising tool to induce protective immunity against corresponding pathogens. Therefore, we generated MVs expressing the spike glycoprotein of MERS-CoV in its full-length (MERS-S) or a truncated, soluble variant of MERS-S (MERS-solS). The genes encoding MERS-S and MERS-solS were cloned into the vaccine strain MVvac2 genome, and the respective viruses were rescued (MVvac2-CoV-S and MVvac2-CoV-solS). These recombinant MVs were amplified and characterized at passages 3 and 10. The replication of MVvac2-CoV-S in Vero cells turned out to be comparable to that of the control virus MVvac2-GFP (encoding green fluorescent protein), while titers of MVvac2-CoV-solS were impaired approximately 3-fold. The genomic stability and expression of the inserted antigens were confirmed via sequencing of viral cDNA and immunoblot analysis. In vivo, immunization of type I interferon receptor-deficient (IFNAR(-/-))-CD46Ge mice with 2 × 10(5) 50% tissue culture infective doses of MVvac2-CoV-S(H) or MVvac2-CoV-solS(H) in a prime-boost regimen induced robust levels of both MV- and MERS-CoV-neutralizing antibodies. Additionally, induction of specific T cells was demonstrated by T cell proliferation, antigen-specific T cell cytotoxicity, and gamma interferon secretion after stimulation of splenocytes with MERS-CoV-S presented by murine dendritic cells. MERS-CoV challenge experiments indicated the protective capacity of these immune responses in vaccinated mice.

DOI: 10.1128/JVI.01815-15
PubMed: 26355094

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pubmed:26355094

Le document en format XML

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<name sortKey="Beissert, Tim" sort="Beissert, Tim" uniqKey="Beissert T" first="Tim" last="Beissert">Tim Beissert</name>
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<wicri:regionArea>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg</wicri:regionArea>
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<name sortKey="Schmidt, Jorg" sort="Schmidt, Jorg" uniqKey="Schmidt J" first="Jörg" last="Schmidt">Jörg Schmidt</name>
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<nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg</wicri:regionArea>
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<name sortKey="Vergara Alert, Julia" sort="Vergara Alert, Julia" uniqKey="Vergara Alert J" first="Júlia" last="Vergara-Alert">Júlia Vergara-Alert</name>
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<nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg</wicri:regionArea>
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<name sortKey="Suzer, Yasemin" sort="Suzer, Yasemin" uniqKey="Suzer Y" first="Yasemin" last="Süzer">Yasemin Süzer</name>
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<nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
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<name sortKey="Seifried, Janna" sort="Seifried, Janna" uniqKey="Seifried J" first="Janna" last="Seifried">Janna Seifried</name>
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<country xml:lang="fr">Allemagne</country>
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<name sortKey="Hanschmann, Kay Martin" sort="Hanschmann, Kay Martin" uniqKey="Hanschmann K" first="Kay-Martin" last="Hanschmann">Kay-Martin Hanschmann</name>
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<name sortKey="Kalinke, Ulrich" sort="Kalinke, Ulrich" uniqKey="Kalinke U" first="Ulrich" last="Kalinke">Ulrich Kalinke</name>
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<nlm:affiliation>Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany German Center for Infection Research, Hannover, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
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<name sortKey="Herold, Susanne" sort="Herold, Susanne" uniqKey="Herold S" first="Susanne" last="Herold">Susanne Herold</name>
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<nlm:affiliation>Universities Gießen and Marburg Lung Center, Department of Internal Medicine II, Section of Infectious Diseases, Giessen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
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<name sortKey="Sahin, Ugur" sort="Sahin, Ugur" uniqKey="Sahin U" first="Ugur" last="Sahin">Ugur Sahin</name>
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<nlm:affiliation>TRON gGmbH, Mainz, Germany Universitätsmedizin Mainz, Mainz, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>TRON gGmbH, Mainz, Germany Universitätsmedizin Mainz, Mainz</wicri:regionArea>
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<region type="land" nuts="2">Rhénanie-Palatinat</region>
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<name sortKey="Cichutek, Klaus" sort="Cichutek, Klaus" uniqKey="Cichutek K" first="Klaus" last="Cichutek">Klaus Cichutek</name>
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<nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany German Center for Infection Research, Langen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
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<name sortKey="Waibler, Zoe" sort="Waibler, Zoe" uniqKey="Waibler Z" first="Zoe" last="Waibler">Zoe Waibler</name>
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<nlm:affiliation>German Center for Infection Research, Langen, Germany Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>German Center for Infection Research, Langen, Germany Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich-Institut, Langen</wicri:regionArea>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
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<name sortKey="Eickmann, Markus" sort="Eickmann, Markus" uniqKey="Eickmann M" first="Markus" last="Eickmann">Markus Eickmann</name>
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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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<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg</wicri:regionArea>
<placeName>
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<name sortKey="Muhlebach, Michael D" sort="Muhlebach, Michael D" uniqKey="Muhlebach M" first="Michael D" last="Mühlebach">Michael D. Mühlebach</name>
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<wicri:noRegion>Langen</wicri:noRegion>
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<title xml:lang="en">A Highly Immunogenic and Protective Middle East Respiratory Syndrome Coronavirus Vaccine Based on a Recombinant Measles Virus Vaccine Platform.</title>
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<name sortKey="Malczyk, Anna H" sort="Malczyk, Anna H" uniqKey="Malczyk A" first="Anna H" last="Malczyk">Anna H. Malczyk</name>
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<name sortKey="Kupke, Alexandra" sort="Kupke, Alexandra" uniqKey="Kupke A" first="Alexandra" last="Kupke">Alexandra Kupke</name>
<affiliation wicri:level="3">
<nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Hesse (Land)</region>
<region type="district" nuts="2">District de Giessen</region>
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<name sortKey="Prufer, Steffen" sort="Prufer, Steffen" uniqKey="Prufer S" first="Steffen" last="Prüfer">Steffen Prüfer</name>
<affiliation wicri:level="1">
<nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen</wicri:regionArea>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
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<name sortKey="Scheuplein, Vivian A" sort="Scheuplein, Vivian A" uniqKey="Scheuplein V" first="Vivian A" last="Scheuplein">Vivian A. Scheuplein</name>
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<nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen</wicri:regionArea>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Hutzler, Stefan" sort="Hutzler, Stefan" uniqKey="Hutzler S" first="Stefan" last="Hutzler">Stefan Hutzler</name>
<affiliation wicri:level="1">
<nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen</wicri:regionArea>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Kreuz, Dorothea" sort="Kreuz, Dorothea" uniqKey="Kreuz D" first="Dorothea" last="Kreuz">Dorothea Kreuz</name>
<affiliation wicri:level="1">
<nlm:affiliation>Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich-Institut, Langen</wicri:regionArea>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Beissert, Tim" sort="Beissert, Tim" uniqKey="Beissert T" first="Tim" last="Beissert">Tim Beissert</name>
<affiliation wicri:level="3">
<nlm:affiliation>TRON gGmbH, Mainz, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>TRON gGmbH, Mainz</wicri:regionArea>
<placeName>
<region type="land" nuts="2">Rhénanie-Palatinat</region>
<settlement type="city">Mayence</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Bauer, Stefanie" sort="Bauer, Stefanie" uniqKey="Bauer S" first="Stefanie" last="Bauer">Stefanie Bauer</name>
<affiliation wicri:level="1">
<nlm:affiliation>Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich-Institut, Langen</wicri:regionArea>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Hubich Rau, Stefanie" sort="Hubich Rau, Stefanie" uniqKey="Hubich Rau S" first="Stefanie" last="Hubich-Rau">Stefanie Hubich-Rau</name>
<affiliation wicri:level="3">
<nlm:affiliation>Universitätsmedizin Mainz, Mainz, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Universitätsmedizin Mainz, Mainz</wicri:regionArea>
<placeName>
<region type="land" nuts="2">Rhénanie-Palatinat</region>
<settlement type="city">Mayence</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Tondera, Christiane" sort="Tondera, Christiane" uniqKey="Tondera C" first="Christiane" last="Tondera">Christiane Tondera</name>
<affiliation wicri:level="1">
<nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen</wicri:regionArea>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Eldin, Hosam Shams" sort="Eldin, Hosam Shams" uniqKey="Eldin H" first="Hosam Shams" last="Eldin">Hosam Shams Eldin</name>
<affiliation wicri:level="3">
<nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, 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>
</author>
<author>
<name sortKey="Schmidt, Jorg" sort="Schmidt, Jorg" uniqKey="Schmidt J" first="Jörg" last="Schmidt">Jörg Schmidt</name>
<affiliation wicri:level="3">
<nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, 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>
</author>
<author>
<name sortKey="Vergara Alert, Julia" sort="Vergara Alert, Julia" uniqKey="Vergara Alert J" first="Júlia" last="Vergara-Alert">Júlia Vergara-Alert</name>
<affiliation wicri:level="3">
<nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, 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>
</author>
<author>
<name sortKey="Suzer, Yasemin" sort="Suzer, Yasemin" uniqKey="Suzer Y" first="Yasemin" last="Süzer">Yasemin Süzer</name>
<affiliation wicri:level="1">
<nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen</wicri:regionArea>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Seifried, Janna" sort="Seifried, Janna" uniqKey="Seifried J" first="Janna" last="Seifried">Janna Seifried</name>
<affiliation wicri:level="1">
<nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen</wicri:regionArea>
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<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Hanschmann, Kay Martin" sort="Hanschmann, Kay Martin" uniqKey="Hanschmann K" first="Kay-Martin" last="Hanschmann">Kay-Martin Hanschmann</name>
<affiliation wicri:level="1">
<nlm:affiliation>Biostatistics, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Biostatistics, Paul-Ehrlich-Institut, Langen</wicri:regionArea>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Kalinke, Ulrich" sort="Kalinke, Ulrich" uniqKey="Kalinke U" first="Ulrich" last="Kalinke">Ulrich Kalinke</name>
<affiliation wicri:level="3">
<nlm:affiliation>Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany German Center for Infection Research, Hannover, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany German Center for Infection Research, Hannover</wicri:regionArea>
<placeName>
<region type="land" nuts="2">Basse-Saxe</region>
<settlement type="city">Hanovre</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Herold, Susanne" sort="Herold, Susanne" uniqKey="Herold S" first="Susanne" last="Herold">Susanne Herold</name>
<affiliation wicri:level="1">
<nlm:affiliation>Universities Gießen and Marburg Lung Center, Department of Internal Medicine II, Section of Infectious Diseases, Giessen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Universities Gießen and Marburg Lung Center, Department of Internal Medicine II, Section of Infectious Diseases, Giessen</wicri:regionArea>
<wicri:noRegion>Giessen</wicri:noRegion>
<wicri:noRegion>Giessen</wicri:noRegion>
<wicri:noRegion>Giessen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Sahin, Ugur" sort="Sahin, Ugur" uniqKey="Sahin U" first="Ugur" last="Sahin">Ugur Sahin</name>
<affiliation wicri:level="3">
<nlm:affiliation>TRON gGmbH, Mainz, Germany Universitätsmedizin Mainz, Mainz, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>TRON gGmbH, Mainz, Germany Universitätsmedizin Mainz, Mainz</wicri:regionArea>
<placeName>
<region type="land" nuts="2">Rhénanie-Palatinat</region>
<settlement type="city">Mayence</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Cichutek, Klaus" sort="Cichutek, Klaus" uniqKey="Cichutek K" first="Klaus" last="Cichutek">Klaus Cichutek</name>
<affiliation wicri:level="1">
<nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany German Center for Infection Research, Langen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany German Center for Infection Research, Langen</wicri:regionArea>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Waibler, Zoe" sort="Waibler, Zoe" uniqKey="Waibler Z" first="Zoe" last="Waibler">Zoe Waibler</name>
<affiliation wicri:level="1">
<nlm:affiliation>German Center for Infection Research, Langen, Germany Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>German Center for Infection Research, Langen, Germany Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich-Institut, Langen</wicri:regionArea>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Eickmann, Markus" sort="Eickmann, Markus" uniqKey="Eickmann M" first="Markus" last="Eickmann">Markus Eickmann</name>
<affiliation wicri:level="3">
<nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, 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>
</author>
<author>
<name sortKey="Becker, Stephan" sort="Becker, Stephan" uniqKey="Becker S" first="Stephan" last="Becker">Stephan Becker</name>
<affiliation wicri:level="3">
<nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, 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>
</author>
<author>
<name sortKey="Muhlebach, Michael D" sort="Muhlebach, Michael D" uniqKey="Muhlebach M" first="Michael D" last="Mühlebach">Michael D. Mühlebach</name>
<affiliation wicri:level="1">
<nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany German Center for Infection Research, Langen, Germany Michael.Muehlebach@pei.de.</nlm:affiliation>
<country wicri:rule="url">Allemagne</country>
<wicri:regionArea>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany German Center for Infection Research, Langen</wicri:regionArea>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
<wicri:noRegion>Langen</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Journal of virology</title>
<idno type="eISSN">1098-5514</idno>
<imprint>
<date when="2015" type="published">2015</date>
</imprint>
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<keywords scheme="KwdEn" xml:lang="en">
<term>Animals</term>
<term>Antibodies, Neutralizing (immunology)</term>
<term>Antibodies, Viral (immunology)</term>
<term>Cell Line</term>
<term>Cell Proliferation</term>
<term>Chlorocebus aethiops</term>
<term>Cloning, Molecular (methods)</term>
<term>Coronavirus Infections (immunology)</term>
<term>Coronavirus Infections (prevention & control)</term>
<term>Dendritic Cells (immunology)</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Immunity, Cellular (immunology)</term>
<term>Interferon-gamma (metabolism)</term>
<term>Measles Vaccine (immunology)</term>
<term>Measles virus (genetics)</term>
<term>Measles virus (immunology)</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Knockout</term>
<term>Middle East Respiratory Syndrome Coronavirus (immunology)</term>
<term>Receptor, Interferon alpha-beta (genetics)</term>
<term>Spike Glycoprotein, Coronavirus (biosynthesis)</term>
<term>Spike Glycoprotein, Coronavirus (genetics)</term>
<term>Spike Glycoprotein, Coronavirus (immunology)</term>
<term>T-Lymphocytes (immunology)</term>
<term>Vaccination</term>
<term>Vero Cells</term>
<term>Viral Vaccines (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Animaux</term>
<term>Anticorps antiviraux (immunologie)</term>
<term>Anticorps neutralisants (immunologie)</term>
<term>Cellules HEK293</term>
<term>Cellules Vero</term>
<term>Cellules dendritiques (immunologie)</term>
<term>Clonage moléculaire ()</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term>
<term>Glycoprotéine de spicule des coronavirus (biosynthèse)</term>
<term>Glycoprotéine de spicule des coronavirus (génétique)</term>
<term>Glycoprotéine de spicule des coronavirus (immunologie)</term>
<term>Humains</term>
<term>Immunité cellulaire (immunologie)</term>
<term>Infections à coronavirus ()</term>
<term>Infections à coronavirus (immunologie)</term>
<term>Interféron gamma (métabolisme)</term>
<term>Lignée cellulaire</term>
<term>Lymphocytes T (immunologie)</term>
<term>Prolifération cellulaire</term>
<term>Récepteur à l'interféron alpha-bêta (génétique)</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Souris knockout</term>
<term>Vaccin contre la rougeole (immunologie)</term>
<term>Vaccination</term>
<term>Vaccins antiviraux (immunologie)</term>
<term>Virus de la rougeole (génétique)</term>
<term>Virus de la rougeole (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en">
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>Receptor, Interferon alpha-beta</term>
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en">
<term>Antibodies, Neutralizing</term>
<term>Antibodies, Viral</term>
<term>Measles Vaccine</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr">
<term>Glycoprotéine de spicule des coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Measles virus</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Récepteur à l'interféron alpha-bêta</term>
<term>Virus de la rougeole</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Anticorps antiviraux</term>
<term>Anticorps neutralisants</term>
<term>Cellules dendritiques</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Immunité cellulaire</term>
<term>Infections à coronavirus</term>
<term>Lymphocytes T</term>
<term>Vaccin contre la rougeole</term>
<term>Vaccins antiviraux</term>
<term>Virus de la rougeole</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>Coronavirus Infections</term>
<term>Dendritic Cells</term>
<term>Immunity, Cellular</term>
<term>Measles virus</term>
<term>Middle East Respiratory Syndrome Coronavirus</term>
<term>T-Lymphocytes</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Interferon-gamma</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en">
<term>Cloning, Molecular</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Interféron gamma</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en">
<term>Coronavirus Infections</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Animals</term>
<term>Cell Line</term>
<term>Cell Proliferation</term>
<term>Chlorocebus aethiops</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Knockout</term>
<term>Vaccination</term>
<term>Vero Cells</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Animaux</term>
<term>Cellules HEK293</term>
<term>Cellules Vero</term>
<term>Clonage moléculaire</term>
<term>Humains</term>
<term>Infections à coronavirus</term>
<term>Lignée cellulaire</term>
<term>Prolifération cellulaire</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Souris knockout</term>
<term>Vaccination</term>
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<front>
<div type="abstract" xml:lang="en">In 2012, the first cases of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) were identified. Since then, more than 1,000 cases of MERS-CoV infection have been confirmed; infection is typically associated with considerable morbidity and, in approximately 30% of cases, mortality. Currently, there is no protective vaccine available. Replication-competent recombinant measles virus (MV) expressing foreign antigens constitutes a promising tool to induce protective immunity against corresponding pathogens. Therefore, we generated MVs expressing the spike glycoprotein of MERS-CoV in its full-length (MERS-S) or a truncated, soluble variant of MERS-S (MERS-solS). The genes encoding MERS-S and MERS-solS were cloned into the vaccine strain MVvac2 genome, and the respective viruses were rescued (MVvac2-CoV-S and MVvac2-CoV-solS). These recombinant MVs were amplified and characterized at passages 3 and 10. The replication of MVvac2-CoV-S in Vero cells turned out to be comparable to that of the control virus MVvac2-GFP (encoding green fluorescent protein), while titers of MVvac2-CoV-solS were impaired approximately 3-fold. The genomic stability and expression of the inserted antigens were confirmed via sequencing of viral cDNA and immunoblot analysis. In vivo, immunization of type I interferon receptor-deficient (IFNAR(-/-))-CD46Ge mice with 2 × 10(5) 50% tissue culture infective doses of MVvac2-CoV-S(H) or MVvac2-CoV-solS(H) in a prime-boost regimen induced robust levels of both MV- and MERS-CoV-neutralizing antibodies. Additionally, induction of specific T cells was demonstrated by T cell proliferation, antigen-specific T cell cytotoxicity, and gamma interferon secretion after stimulation of splenocytes with MERS-CoV-S presented by murine dendritic cells. MERS-CoV challenge experiments indicated the protective capacity of these immune responses in vaccinated mice.</div>
</front>
</TEI>
<pubmed>
<MedlineCitation Status="MEDLINE" Owner="NLM">
<PMID Version="1">26355094</PMID>
<DateCompleted>
<Year>2016</Year>
<Month>01</Month>
<Day>29</Day>
</DateCompleted>
<DateRevised>
<Year>2019</Year>
<Month>12</Month>
<Day>10</Day>
</DateRevised>
<Article PubModel="Print-Electronic">
<Journal>
<ISSN IssnType="Electronic">1098-5514</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>89</Volume>
<Issue>22</Issue>
<PubDate>
<Year>2015</Year>
<Month>Nov</Month>
</PubDate>
</JournalIssue>
<Title>Journal of virology</Title>
<ISOAbbreviation>J. Virol.</ISOAbbreviation>
</Journal>
<ArticleTitle>A Highly Immunogenic and Protective Middle East Respiratory Syndrome Coronavirus Vaccine Based on a Recombinant Measles Virus Vaccine Platform.</ArticleTitle>
<Pagination>
<MedlinePgn>11654-67</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1128/JVI.01815-15</ELocationID>
<Abstract>
<AbstractText Label="UNLABELLED">In 2012, the first cases of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) were identified. Since then, more than 1,000 cases of MERS-CoV infection have been confirmed; infection is typically associated with considerable morbidity and, in approximately 30% of cases, mortality. Currently, there is no protective vaccine available. Replication-competent recombinant measles virus (MV) expressing foreign antigens constitutes a promising tool to induce protective immunity against corresponding pathogens. Therefore, we generated MVs expressing the spike glycoprotein of MERS-CoV in its full-length (MERS-S) or a truncated, soluble variant of MERS-S (MERS-solS). The genes encoding MERS-S and MERS-solS were cloned into the vaccine strain MVvac2 genome, and the respective viruses were rescued (MVvac2-CoV-S and MVvac2-CoV-solS). These recombinant MVs were amplified and characterized at passages 3 and 10. The replication of MVvac2-CoV-S in Vero cells turned out to be comparable to that of the control virus MVvac2-GFP (encoding green fluorescent protein), while titers of MVvac2-CoV-solS were impaired approximately 3-fold. The genomic stability and expression of the inserted antigens were confirmed via sequencing of viral cDNA and immunoblot analysis. In vivo, immunization of type I interferon receptor-deficient (IFNAR(-/-))-CD46Ge mice with 2 × 10(5) 50% tissue culture infective doses of MVvac2-CoV-S(H) or MVvac2-CoV-solS(H) in a prime-boost regimen induced robust levels of both MV- and MERS-CoV-neutralizing antibodies. Additionally, induction of specific T cells was demonstrated by T cell proliferation, antigen-specific T cell cytotoxicity, and gamma interferon secretion after stimulation of splenocytes with MERS-CoV-S presented by murine dendritic cells. MERS-CoV challenge experiments indicated the protective capacity of these immune responses in vaccinated mice.</AbstractText>
<AbstractText Label="IMPORTANCE" NlmCategory="OBJECTIVE">Although MERS-CoV has not yet acquired extensive distribution, being mainly confined to the Arabic and Korean peninsulas, it could adapt to spread more readily among humans and thereby become pandemic. Therefore, the development of a vaccine is mandatory. The integration of antigen-coding genes into recombinant MV resulting in coexpression of MV and foreign antigens can efficiently be achieved. Thus, in combination with the excellent safety profile of the MV vaccine, recombinant MV seems to constitute an ideal vaccine platform. The present study shows that a recombinant MV expressing MERS-S is genetically stable and induces strong humoral and cellular immunity against MERS-CoV in vaccinated mice. Subsequent challenge experiments indicated protection of vaccinated animals, illustrating the potential of MV as a vaccine platform with the potential to target emerging infections, such as MERS-CoV.</AbstractText>
<CopyrightInformation>Copyright © 2015, American Society for Microbiology. All Rights Reserved.</CopyrightInformation>
</Abstract>
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<Initials>AH</Initials>
<AffiliationInfo>
<Affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany German Center for Infection Research, Langen, Germany.</Affiliation>
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<Affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</Affiliation>
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<Affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</Affiliation>
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<LastName>Scheuplein</LastName>
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<Affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</Affiliation>
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<LastName>Hubich-Rau</LastName>
<ForeName>Stefanie</ForeName>
<Initials>S</Initials>
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<Affiliation>Universitätsmedizin Mainz, Mainz, Germany.</Affiliation>
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<LastName>Eldin</LastName>
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<Affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</Affiliation>
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<Affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</Affiliation>
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<LastName>Süzer</LastName>
<ForeName>Yasemin</ForeName>
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<Affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</Affiliation>
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<Affiliation>Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany German Center for Infection Research, Hannover, Germany.</Affiliation>
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<Affiliation>Universities Gießen and Marburg Lung Center, Department of Internal Medicine II, Section of Infectious Diseases, Giessen, Germany.</Affiliation>
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<LastName>Sahin</LastName>
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<Affiliation>TRON gGmbH, Mainz, Germany Universitätsmedizin Mainz, Mainz, Germany.</Affiliation>
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<LastName>Cichutek</LastName>
<ForeName>Klaus</ForeName>
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<LastName>Waibler</LastName>
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<Affiliation>German Center for Infection Research, Langen, Germany Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich-Institut, Langen, Germany.</Affiliation>
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<LastName>Becker</LastName>
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<LastName>Mühlebach</LastName>
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<Language>eng</Language>
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<Year>2015</Year>
<Month>09</Month>
<Day>09</Day>
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<MedlineTA>J Virol</MedlineTA>
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<ISSNLinking>0022-538X</ISSNLinking>
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<DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D057134" MajorTopicYN="N">Antibodies, Neutralizing</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
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<MeshHeading>
<DescriptorName UI="D000914" MajorTopicYN="N">Antibodies, Viral</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
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<MeshHeading>
<DescriptorName UI="D002460" MajorTopicYN="N">Cell Line</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName>
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<DescriptorName UI="D002522" MajorTopicYN="N">Chlorocebus aethiops</DescriptorName>
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<DescriptorName UI="D003001" MajorTopicYN="N">Cloning, Molecular</DescriptorName>
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<DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName>
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<QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName>
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<DescriptorName UI="D003713" MajorTopicYN="N">Dendritic Cells</DescriptorName>
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<DescriptorName UI="D057809" MajorTopicYN="N">HEK293 Cells</DescriptorName>
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<DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
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<DescriptorName UI="D007111" MajorTopicYN="N">Immunity, Cellular</DescriptorName>
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<DescriptorName UI="D007371" MajorTopicYN="N">Interferon-gamma</DescriptorName>
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<DescriptorName UI="D008458" MajorTopicYN="N">Measles Vaccine</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
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<DescriptorName UI="D008459" MajorTopicYN="N">Measles virus</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
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<DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
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<DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D018345" MajorTopicYN="N">Mice, Knockout</DescriptorName>
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<DescriptorName UI="D053633" MajorTopicYN="N">Receptor, Interferon alpha-beta</DescriptorName>
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<Day>16</Day>
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<Year>2015</Year>
<Month>09</Month>
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<Month>9</Month>
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