MersV1, PubMed, Corpus, bibRecord, 001473

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

Identifieur interne : 001473 ( PubMed/Corpus ); précédent : 001472; suivant : 001474

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

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

Source :

Journal of virology [ 1098-5514 ] ; 2015.

RBID : pubmed:26355094

English descriptors

KwdEn :
- Animals, Antibodies, Neutralizing (immunology), Antibodies, Viral (immunology), Cell Line, Cell Proliferation, Chlorocebus aethiops, Cloning, Molecular (methods), Coronavirus Infections (immunology), Coronavirus Infections (prevention & control), Dendritic Cells (immunology), HEK293 Cells, Humans, Immunity, Cellular (immunology), Interferon-gamma (metabolism), Measles Vaccine (immunology), Measles virus (genetics), Measles virus (immunology), Mice, Mice, Inbred C57BL, Mice, Knockout, Middle East Respiratory Syndrome Coronavirus (immunology), Receptor, Interferon alpha-beta (genetics), Spike Glycoprotein, Coronavirus (biosynthesis), Spike Glycoprotein, Coronavirus (genetics), Spike Glycoprotein, Coronavirus (immunology), T-Lymphocytes (immunology), Vaccination, Vero Cells, Viral Vaccines (immunology).
MESH :
- chemical , biosynthesis : Spike Glycoprotein, Coronavirus.
- chemical , genetics : Receptor, Interferon alpha-beta, Spike Glycoprotein, Coronavirus.
- chemical , immunology : Antibodies, Neutralizing, Antibodies, Viral, Measles Vaccine, Spike Glycoprotein, Coronavirus, Viral Vaccines.
- genetics : Measles virus.
- immunology : Coronavirus Infections, Dendritic Cells, Immunity, Cellular, Measles virus, Middle East Respiratory Syndrome Coronavirus, T-Lymphocytes.
- chemical , metabolism : Interferon-gamma.
- methods : Cloning, Molecular.
- prevention & control : Coronavirus Infections.
- Animals, Cell Line, Cell Proliferation, Chlorocebus aethiops, HEK293 Cells, Humans, Mice, Mice, Inbred C57BL, Mice, Knockout, Vaccination, Vero Cells.

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

Links to Exploration step

pubmed:26355094

Le document en format XML

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<author><name sortKey="Malczyk, Anna H" sort="Malczyk, Anna H" uniqKey="Malczyk A" first="Anna H" last="Malczyk">Anna H. Malczyk</name>
<affiliation><nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany German Center for Infection Research, Langen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kupke, Alexandra" sort="Kupke, Alexandra" uniqKey="Kupke A" first="Alexandra" last="Kupke">Alexandra Kupke</name>
<affiliation><nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Prufer, Steffen" sort="Prufer, Steffen" uniqKey="Prufer S" first="Steffen" last="Prüfer">Steffen Prüfer</name>
<affiliation><nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Scheuplein, Vivian A" sort="Scheuplein, Vivian A" uniqKey="Scheuplein V" first="Vivian A" last="Scheuplein">Vivian A. Scheuplein</name>
<affiliation><nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Hutzler, Stefan" sort="Hutzler, Stefan" uniqKey="Hutzler S" first="Stefan" last="Hutzler">Stefan Hutzler</name>
<affiliation><nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kreuz, Dorothea" sort="Kreuz, Dorothea" uniqKey="Kreuz D" first="Dorothea" last="Kreuz">Dorothea Kreuz</name>
<affiliation><nlm:affiliation>Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Beissert, Tim" sort="Beissert, Tim" uniqKey="Beissert T" first="Tim" last="Beissert">Tim Beissert</name>
<affiliation><nlm:affiliation>TRON gGmbH, Mainz, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Bauer, Stefanie" sort="Bauer, Stefanie" uniqKey="Bauer S" first="Stefanie" last="Bauer">Stefanie Bauer</name>
<affiliation><nlm:affiliation>Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
</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><nlm:affiliation>Universitätsmedizin Mainz, Mainz, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Tondera, Christiane" sort="Tondera, Christiane" uniqKey="Tondera C" first="Christiane" last="Tondera">Christiane Tondera</name>
<affiliation><nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
</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><nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Schmidt, Jorg" sort="Schmidt, Jorg" uniqKey="Schmidt J" first="Jörg" last="Schmidt">Jörg Schmidt</name>
<affiliation><nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</nlm:affiliation>
</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><nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Suzer, Yasemin" sort="Suzer, Yasemin" uniqKey="Suzer Y" first="Yasemin" last="Süzer">Yasemin Süzer</name>
<affiliation><nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Seifried, Janna" sort="Seifried, Janna" uniqKey="Seifried J" first="Janna" last="Seifried">Janna Seifried</name>
<affiliation><nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
</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><nlm:affiliation>Biostatistics, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kalinke, Ulrich" sort="Kalinke, Ulrich" uniqKey="Kalinke U" first="Ulrich" last="Kalinke">Ulrich Kalinke</name>
<affiliation><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>
</affiliation>
</author>
<author><name sortKey="Herold, Susanne" sort="Herold, Susanne" uniqKey="Herold S" first="Susanne" last="Herold">Susanne Herold</name>
<affiliation><nlm:affiliation>Universities Gießen and Marburg Lung Center, Department of Internal Medicine II, Section of Infectious Diseases, Giessen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Sahin, Ugur" sort="Sahin, Ugur" uniqKey="Sahin U" first="Ugur" last="Sahin">Ugur Sahin</name>
<affiliation><nlm:affiliation>TRON gGmbH, Mainz, Germany Universitätsmedizin Mainz, Mainz, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Cichutek, Klaus" sort="Cichutek, Klaus" uniqKey="Cichutek K" first="Klaus" last="Cichutek">Klaus Cichutek</name>
<affiliation><nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany German Center for Infection Research, Langen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Waibler, Zoe" sort="Waibler, Zoe" uniqKey="Waibler Z" first="Zoe" last="Waibler">Zoe Waibler</name>
<affiliation><nlm:affiliation>German Center for Infection Research, Langen, Germany Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Eickmann, Markus" sort="Eickmann, Markus" uniqKey="Eickmann M" first="Markus" last="Eickmann">Markus Eickmann</name>
<affiliation><nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Becker, Stephan" sort="Becker, Stephan" uniqKey="Becker S" first="Stephan" last="Becker">Stephan Becker</name>
<affiliation><nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</nlm:affiliation>
</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><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>
</affiliation>
</author>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">A Highly Immunogenic and Protective Middle East Respiratory Syndrome Coronavirus Vaccine Based on a Recombinant Measles Virus Vaccine Platform.</title>
<author><name sortKey="Malczyk, Anna H" sort="Malczyk, Anna H" uniqKey="Malczyk A" first="Anna H" last="Malczyk">Anna H. Malczyk</name>
<affiliation><nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany German Center for Infection Research, Langen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kupke, Alexandra" sort="Kupke, Alexandra" uniqKey="Kupke A" first="Alexandra" last="Kupke">Alexandra Kupke</name>
<affiliation><nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Prufer, Steffen" sort="Prufer, Steffen" uniqKey="Prufer S" first="Steffen" last="Prüfer">Steffen Prüfer</name>
<affiliation><nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Scheuplein, Vivian A" sort="Scheuplein, Vivian A" uniqKey="Scheuplein V" first="Vivian A" last="Scheuplein">Vivian A. Scheuplein</name>
<affiliation><nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Hutzler, Stefan" sort="Hutzler, Stefan" uniqKey="Hutzler S" first="Stefan" last="Hutzler">Stefan Hutzler</name>
<affiliation><nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kreuz, Dorothea" sort="Kreuz, Dorothea" uniqKey="Kreuz D" first="Dorothea" last="Kreuz">Dorothea Kreuz</name>
<affiliation><nlm:affiliation>Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Beissert, Tim" sort="Beissert, Tim" uniqKey="Beissert T" first="Tim" last="Beissert">Tim Beissert</name>
<affiliation><nlm:affiliation>TRON gGmbH, Mainz, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Bauer, Stefanie" sort="Bauer, Stefanie" uniqKey="Bauer S" first="Stefanie" last="Bauer">Stefanie Bauer</name>
<affiliation><nlm:affiliation>Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
</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><nlm:affiliation>Universitätsmedizin Mainz, Mainz, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Tondera, Christiane" sort="Tondera, Christiane" uniqKey="Tondera C" first="Christiane" last="Tondera">Christiane Tondera</name>
<affiliation><nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
</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><nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Schmidt, Jorg" sort="Schmidt, Jorg" uniqKey="Schmidt J" first="Jörg" last="Schmidt">Jörg Schmidt</name>
<affiliation><nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</nlm:affiliation>
</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><nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Suzer, Yasemin" sort="Suzer, Yasemin" uniqKey="Suzer Y" first="Yasemin" last="Süzer">Yasemin Süzer</name>
<affiliation><nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Seifried, Janna" sort="Seifried, Janna" uniqKey="Seifried J" first="Janna" last="Seifried">Janna Seifried</name>
<affiliation><nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
</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><nlm:affiliation>Biostatistics, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kalinke, Ulrich" sort="Kalinke, Ulrich" uniqKey="Kalinke U" first="Ulrich" last="Kalinke">Ulrich Kalinke</name>
<affiliation><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>
</affiliation>
</author>
<author><name sortKey="Herold, Susanne" sort="Herold, Susanne" uniqKey="Herold S" first="Susanne" last="Herold">Susanne Herold</name>
<affiliation><nlm:affiliation>Universities Gießen and Marburg Lung Center, Department of Internal Medicine II, Section of Infectious Diseases, Giessen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Sahin, Ugur" sort="Sahin, Ugur" uniqKey="Sahin U" first="Ugur" last="Sahin">Ugur Sahin</name>
<affiliation><nlm:affiliation>TRON gGmbH, Mainz, Germany Universitätsmedizin Mainz, Mainz, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Cichutek, Klaus" sort="Cichutek, Klaus" uniqKey="Cichutek K" first="Klaus" last="Cichutek">Klaus Cichutek</name>
<affiliation><nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany German Center for Infection Research, Langen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Waibler, Zoe" sort="Waibler, Zoe" uniqKey="Waibler Z" first="Zoe" last="Waibler">Zoe Waibler</name>
<affiliation><nlm:affiliation>German Center for Infection Research, Langen, Germany Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich-Institut, Langen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Eickmann, Markus" sort="Eickmann, Markus" uniqKey="Eickmann M" first="Markus" last="Eickmann">Markus Eickmann</name>
<affiliation><nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Becker, Stephan" sort="Becker, Stephan" uniqKey="Becker S" first="Stephan" last="Becker">Stephan Becker</name>
<affiliation><nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</nlm:affiliation>
</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><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>
</affiliation>
</author>
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<idno type="eISSN">1098-5514</idno>
<imprint><date when="2015" type="published">2015</date>
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<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="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="genetics" xml:lang="en"><term>Measles virus</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>
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</keywords>
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</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>
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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>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Malczyk</LastName>
<ForeName>Anna H</ForeName>
<Initials>AH</Initials>
<AffiliationInfo><Affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany German Center for Infection Research, Langen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kupke</LastName>
<ForeName>Alexandra</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Prüfer</LastName>
<ForeName>Steffen</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Scheuplein</LastName>
<ForeName>Vivian A</ForeName>
<Initials>VA</Initials>
<AffiliationInfo><Affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hutzler</LastName>
<ForeName>Stefan</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kreuz</LastName>
<ForeName>Dorothea</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich-Institut, Langen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Beissert</LastName>
<ForeName>Tim</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>TRON gGmbH, Mainz, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bauer</LastName>
<ForeName>Stefanie</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich-Institut, Langen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hubich-Rau</LastName>
<ForeName>Stefanie</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Universitätsmedizin Mainz, Mainz, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tondera</LastName>
<ForeName>Christiane</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Eldin</LastName>
<ForeName>Hosam Shams</ForeName>
<Initials>HS</Initials>
<AffiliationInfo><Affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Schmidt</LastName>
<ForeName>Jörg</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Vergara-Alert</LastName>
<ForeName>Júlia</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Süzer</LastName>
<ForeName>Yasemin</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Seifried</LastName>
<ForeName>Janna</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hanschmann</LastName>
<ForeName>Kay-Martin</ForeName>
<Initials>KM</Initials>
<AffiliationInfo><Affiliation>Biostatistics, Paul-Ehrlich-Institut, Langen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kalinke</LastName>
<ForeName>Ulrich</ForeName>
<Initials>U</Initials>
<AffiliationInfo><Affiliation>Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany German Center for Infection Research, Hannover, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Herold</LastName>
<ForeName>Susanne</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Universities Gießen and Marburg Lung Center, Department of Internal Medicine II, Section of Infectious Diseases, Giessen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sahin</LastName>
<ForeName>Ugur</ForeName>
<Initials>U</Initials>
<AffiliationInfo><Affiliation>TRON gGmbH, Mainz, Germany Universitätsmedizin Mainz, Mainz, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cichutek</LastName>
<ForeName>Klaus</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany German Center for Infection Research, Langen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Waibler</LastName>
<ForeName>Zoe</ForeName>
<Initials>Z</Initials>
<AffiliationInfo><Affiliation>German Center for Infection Research, Langen, Germany Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich-Institut, Langen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Eickmann</LastName>
<ForeName>Markus</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Becker</LastName>
<ForeName>Stephan</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Center for Infection Research, Marburg, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mühlebach</LastName>
<ForeName>Michael D</ForeName>
<Initials>MD</Initials>
<AffiliationInfo><Affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Langen, Germany German Center for Infection Research, Langen, Germany Michael.Muehlebach@pei.de.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2015</Year>
<Month>09</Month>
<Day>09</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>J Virol</MedlineTA>
<NlmUniqueID>0113724</NlmUniqueID>
<ISSNLinking>0022-538X</ISSNLinking>
</MedlineJournalInfo>
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<NameOfSubstance UI="D057134">Antibodies, Neutralizing</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000914">Antibodies, Viral</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C508032">Ifnar1 protein, mouse</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D008458">Measles Vaccine</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D064370">Spike Glycoprotein, Coronavirus</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014765">Viral Vaccines</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>156986-95-7</RegistryNumber>
<NameOfSubstance UI="D053633">Receptor, Interferon alpha-beta</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>82115-62-6</RegistryNumber>
<NameOfSubstance UI="D007371">Interferon-gamma</NameOfSubstance>
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<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D057134" MajorTopicYN="N">Antibodies, Neutralizing</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000914" MajorTopicYN="N">Antibodies, Viral</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002460" MajorTopicYN="N">Cell Line</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002522" MajorTopicYN="N">Chlorocebus aethiops</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D003001" MajorTopicYN="N">Cloning, Molecular</DescriptorName>
<QualifierName UI="Q000379" MajorTopicYN="N">methods</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="D003713" MajorTopicYN="N">Dendritic Cells</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D057809" MajorTopicYN="N">HEK293 Cells</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007111" MajorTopicYN="N">Immunity, Cellular</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007371" MajorTopicYN="N">Interferon-gamma</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008458" MajorTopicYN="N">Measles Vaccine</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008459" MajorTopicYN="N">Measles virus</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018345" MajorTopicYN="N">Mice, Knockout</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D065207" MajorTopicYN="N">Middle East Respiratory Syndrome Coronavirus</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D053633" MajorTopicYN="N">Receptor, Interferon alpha-beta</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D064370" MajorTopicYN="N">Spike Glycoprotein, Coronavirus</DescriptorName>
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<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013601" MajorTopicYN="N">T-Lymphocytes</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014611" MajorTopicYN="N">Vaccination</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014709" MajorTopicYN="N">Vero Cells</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014765" MajorTopicYN="N">Viral Vaccines</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
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<Month>09</Month>
<Day>03</Day>
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A Highly Immunogenic and Protective Middle East Respiratory Syndrome Coronavirus Vaccine Based on a Recombinant Measles Virus Vaccine Platform.

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

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