A Highly Immunogenic and Protective Middle East Respiratory Syndrome Coronavirus Vaccine Based on a Recombinant Measles Virus Vaccine Platform.
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Authors
Malczyk, Anna HKupke, Alexandra
Prüfer, Steffen
Scheuplein, Vivian A
Hutzler, Stefan
Kreuz, Dorothea
Beissert, Tim
Bauer, Stefanie
Hubich-Rau, Stefanie
Tondera, Christiane
Eldin, Hosam Shams
Schmidt, Jörg
Vergara-Alert, Júlia
Süzer, Yasemin
Seifried, Janna
Hanschmann, Kay-Martin
Kalinke, Ulrich
Herold, Susanne
Sahin, Ugur
Cichutek, Klaus
Waibler, Zoe
Eickmann, Markus
Becker, Stephan
Mühlebach, Michael D
Issue Date
2015-11-15
Metadata
Show full item recordAbstract
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.Citation
A Highly Immunogenic and Protective Middle East Respiratory Syndrome Coronavirus Vaccine Based on a Recombinant Measles Virus Vaccine Platform. 2015, 89 (22):11654-67 J. Virol.Affiliation
TWINCORE, Centre for Experimental and Clinical Infection Research GmbH, Feodor-Lynen-Str. 3-7, 30625 Hannover, Germany.Journal
Journal of virologyPubMed ID
26355094Type
ArticleLanguage
enISSN
1098-5514ae974a485f413a2113503eed53cd6c53
10.1128/JVI.01815-15
Scopus Count
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