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<title xml:lang="en">A poxvirus-based vaccine reduces virus excretion after MERS coronavirus infection in dromedary camels</title>
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<name sortKey="Stalin Raj, V" sort="Stalin Raj, V" uniqKey="Stalin Raj V" first="V." last="Stalin Raj">V. Stalin Raj</name>
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<nlm:aff id="aff0005">Erasmus Medical center, Rotterdam, Netherlands</nlm:aff>
</affiliation>
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<author>
<name sortKey="Van Den Brand, J M A" sort="Van Den Brand, J M A" uniqKey="Van Den Brand J" first="J. M. A." last="Van Den Brand">J. M. A. Van Den Brand</name>
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<name sortKey="Volz, A" sort="Volz, A" uniqKey="Volz A" first="A." last="Volz">A. Volz</name>
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<nlm:aff id="aff0010">LMU University of Munich, Munich, Germany</nlm:aff>
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<name sortKey="Wohlsein, P" sort="Wohlsein, P" uniqKey="Wohlsein P" first="P." last="Wohlsein">P. Wohlsein</name>
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<nlm:aff id="aff0015">University of Veterinary Medicine, Hanover, Germany</nlm:aff>
</affiliation>
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<name sortKey="Smits, S L" sort="Smits, S L" uniqKey="Smits S" first="S. L." last="Smits">S. L. Smits</name>
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</affiliation>
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<name sortKey="Okba, N" sort="Okba, N" uniqKey="Okba N" first="N." last="Okba">N. Okba</name>
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</affiliation>
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<name sortKey="Fux, R" sort="Fux, R" uniqKey="Fux R" first="R." last="Fux">R. Fux</name>
<affiliation>
<nlm:aff id="aff0010">LMU University of Munich, Munich, Germany</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Moise Bensaid, A" sort="Moise Bensaid, A" uniqKey="Moise Bensaid A" first="A." last="Moise Bensaid">A. Moise Bensaid</name>
<affiliation>
<nlm:aff id="aff0020">Centre de Recerca en Sanitat Animal, Barcelona, Spain</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Solanes Foz, D" sort="Solanes Foz, D" uniqKey="Solanes Foz D" first="D." last="Solanes Foz">D. Solanes Foz</name>
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<nlm:aff id="aff0020">Centre de Recerca en Sanitat Animal, Barcelona, Spain</nlm:aff>
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<name sortKey="Kuiken, T" sort="Kuiken, T" uniqKey="Kuiken T" first="T." last="Kuiken">T. Kuiken</name>
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<nlm:aff id="aff0005">Erasmus Medical center, Rotterdam, Netherlands</nlm:aff>
</affiliation>
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<author>
<name sortKey="Baumg Rtner, W" sort="Baumg Rtner, W" uniqKey="Baumg Rtner W" first="W." last="Baumg Rtner">W. Baumg Rtner</name>
<affiliation>
<nlm:aff id="aff0015">University of Veterinary Medicine, Hanover, Germany</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Segales, J" sort="Segales, J" uniqKey="Segales J" first="J." last="Segalés">J. Segalés</name>
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<nlm:aff id="aff0020">Centre de Recerca en Sanitat Animal, Barcelona, Spain</nlm:aff>
</affiliation>
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<author>
<name sortKey="Sutter, G" sort="Sutter, G" uniqKey="Sutter G" first="G." last="Sutter">G. Sutter</name>
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<nlm:aff id="aff0010">LMU University of Munich, Munich, Germany</nlm:aff>
</affiliation>
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<author>
<name sortKey="Osterhaus, A D M E" sort="Osterhaus, A D M E" uniqKey="Osterhaus A" first="A. D. M. E." last="Osterhaus">A. D. M. E. Osterhaus</name>
<affiliation>
<nlm:aff id="aff0015">University of Veterinary Medicine, Hanover, Germany</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="L Haagmans, B" sort="L Haagmans, B" uniqKey="L Haagmans B" first="B." last="L Haagmans">B. L Haagmans</name>
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<nlm:aff id="aff0005">Erasmus Medical center, Rotterdam, Netherlands</nlm:aff>
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<title xml:lang="en" level="a" type="main">A poxvirus-based vaccine reduces virus excretion after MERS coronavirus infection in dromedary camels</title>
<author>
<name sortKey="Stalin Raj, V" sort="Stalin Raj, V" uniqKey="Stalin Raj V" first="V." last="Stalin Raj">V. Stalin Raj</name>
<affiliation>
<nlm:aff id="aff0005">Erasmus Medical center, Rotterdam, Netherlands</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Van Den Brand, J M A" sort="Van Den Brand, J M A" uniqKey="Van Den Brand J" first="J. M. A." last="Van Den Brand">J. M. A. Van Den Brand</name>
<affiliation>
<nlm:aff id="aff0005">Erasmus Medical center, Rotterdam, Netherlands</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Volz, A" sort="Volz, A" uniqKey="Volz A" first="A." last="Volz">A. Volz</name>
<affiliation>
<nlm:aff id="aff0010">LMU University of Munich, Munich, Germany</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Wohlsein, P" sort="Wohlsein, P" uniqKey="Wohlsein P" first="P." last="Wohlsein">P. Wohlsein</name>
<affiliation>
<nlm:aff id="aff0015">University of Veterinary Medicine, Hanover, Germany</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Smits, S L" sort="Smits, S L" uniqKey="Smits S" first="S. L." last="Smits">S. L. Smits</name>
<affiliation>
<nlm:aff id="aff0005">Erasmus Medical center, Rotterdam, Netherlands</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Okba, N" sort="Okba, N" uniqKey="Okba N" first="N." last="Okba">N. Okba</name>
<affiliation>
<nlm:aff id="aff0005">Erasmus Medical center, Rotterdam, Netherlands</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Fux, R" sort="Fux, R" uniqKey="Fux R" first="R." last="Fux">R. Fux</name>
<affiliation>
<nlm:aff id="aff0010">LMU University of Munich, Munich, Germany</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Moise Bensaid, A" sort="Moise Bensaid, A" uniqKey="Moise Bensaid A" first="A." last="Moise Bensaid">A. Moise Bensaid</name>
<affiliation>
<nlm:aff id="aff0020">Centre de Recerca en Sanitat Animal, Barcelona, Spain</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Solanes Foz, D" sort="Solanes Foz, D" uniqKey="Solanes Foz D" first="D." last="Solanes Foz">D. Solanes Foz</name>
<affiliation>
<nlm:aff id="aff0020">Centre de Recerca en Sanitat Animal, Barcelona, Spain</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Kuiken, T" sort="Kuiken, T" uniqKey="Kuiken T" first="T." last="Kuiken">T. Kuiken</name>
<affiliation>
<nlm:aff id="aff0005">Erasmus Medical center, Rotterdam, Netherlands</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Baumg Rtner, W" sort="Baumg Rtner, W" uniqKey="Baumg Rtner W" first="W." last="Baumg Rtner">W. Baumg Rtner</name>
<affiliation>
<nlm:aff id="aff0015">University of Veterinary Medicine, Hanover, Germany</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Segales, J" sort="Segales, J" uniqKey="Segales J" first="J." last="Segalés">J. Segalés</name>
<affiliation>
<nlm:aff id="aff0020">Centre de Recerca en Sanitat Animal, Barcelona, Spain</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Sutter, G" sort="Sutter, G" uniqKey="Sutter G" first="G." last="Sutter">G. Sutter</name>
<affiliation>
<nlm:aff id="aff0010">LMU University of Munich, Munich, Germany</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Osterhaus, A D M E" sort="Osterhaus, A D M E" uniqKey="Osterhaus A" first="A. D. M. E." last="Osterhaus">A. D. M. E. Osterhaus</name>
<affiliation>
<nlm:aff id="aff0015">University of Veterinary Medicine, Hanover, Germany</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="L Haagmans, B" sort="L Haagmans, B" uniqKey="L Haagmans B" first="B." last="L Haagmans">B. L Haagmans</name>
<affiliation>
<nlm:aff id="aff0005">Erasmus Medical center, Rotterdam, Netherlands</nlm:aff>
</affiliation>
</author>
</analytic>
<series>
<title level="j">International Journal of Infectious Diseases</title>
<idno type="ISSN">1201-9712</idno>
<idno type="eISSN">1878-3511</idno>
<imprint>
<date when="2016">2016</date>
</imprint>
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<pmc article-type="abstract">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Int J Infect Dis</journal-id>
<journal-id journal-id-type="iso-abbrev">Int. J. Infect. Dis</journal-id>
<journal-title-group>
<journal-title>International Journal of Infectious Diseases</journal-title>
</journal-title-group>
<issn pub-type="ppub">1201-9712</issn>
<issn pub-type="epub">1878-3511</issn>
<publisher>
<publisher-name>Published by Elsevier Ltd.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmc">7128089</article-id>
<article-id pub-id-type="publisher-id">S1201-9712(16)30877-3</article-id>
<article-id pub-id-type="doi">10.1016/j.ijid.2016.02.898</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>A poxvirus-based vaccine reduces virus excretion after MERS coronavirus infection in dromedary camels</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" id="aut0005">
<name>
<surname>Stalin Raj</surname>
<given-names>V.</given-names>
</name>
<xref rid="aff0005" ref-type="aff">1</xref>
<xref rid="cor0005" ref-type="corresp"></xref>
</contrib>
<contrib contrib-type="author" id="aut0010">
<name>
<surname>van den Brand</surname>
<given-names>J.M.A.</given-names>
</name>
<xref rid="aff0005" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author" id="aut0015">
<name>
<surname>Volz</surname>
<given-names>A.</given-names>
</name>
<xref rid="aff0010" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author" id="aut0020">
<name>
<surname>Wohlsein</surname>
<given-names>P.</given-names>
</name>
<xref rid="aff0015" ref-type="aff">3</xref>
</contrib>
<contrib contrib-type="author" id="aut0025">
<name>
<surname>Smits</surname>
<given-names>S.L.</given-names>
</name>
<xref rid="aff0005" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author" id="aut0030">
<name>
<surname>Okba</surname>
<given-names>N.</given-names>
</name>
<xref rid="aff0005" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author" id="aut0035">
<name>
<surname>Fux</surname>
<given-names>R.</given-names>
</name>
<xref rid="aff0010" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author" id="aut0040">
<name>
<surname>Moise Bensaid</surname>
<given-names>A.</given-names>
</name>
<xref rid="aff0020" ref-type="aff">4</xref>
</contrib>
<contrib contrib-type="author" id="aut0045">
<name>
<surname>Solanes Foz</surname>
<given-names>D.</given-names>
</name>
<xref rid="aff0020" ref-type="aff">4</xref>
</contrib>
<contrib contrib-type="author" id="aut0050">
<name>
<surname>Kuiken</surname>
<given-names>T.</given-names>
</name>
<xref rid="aff0005" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author" id="aut0055">
<name>
<surname>Baumgärtner</surname>
<given-names>W.</given-names>
</name>
<xref rid="aff0015" ref-type="aff">3</xref>
</contrib>
<contrib contrib-type="author" id="aut0060">
<name>
<surname>Segalés</surname>
<given-names>J.</given-names>
</name>
<xref rid="aff0020" ref-type="aff">4</xref>
</contrib>
<contrib contrib-type="author" id="aut0065">
<name>
<surname>Sutter</surname>
<given-names>G.</given-names>
</name>
<xref rid="aff0010" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author" id="aut0070">
<name>
<surname>Osterhaus</surname>
<given-names>A.D.M.E.</given-names>
</name>
<xref rid="aff0015" ref-type="aff">3</xref>
</contrib>
<contrib contrib-type="author" id="aut0075">
<name>
<surname>L Haagmans</surname>
<given-names>B.</given-names>
</name>
<xref rid="aff0005" ref-type="aff">1</xref>
</contrib>
</contrib-group>
<aff id="aff0005">
<label>1</label>
Erasmus Medical center, Rotterdam, Netherlands</aff>
<aff id="aff0010">
<label>2</label>
LMU University of Munich, Munich, Germany</aff>
<aff id="aff0015">
<label>3</label>
University of Veterinary Medicine, Hanover, Germany</aff>
<aff id="aff0020">
<label>4</label>
Centre de Recerca en Sanitat Animal, Barcelona, Spain</aff>
<author-notes>
<corresp id="cor0005">
<label></label>
Corresponding author.</corresp>
</author-notes>
<pub-date pub-type="pmc-release">
<day>29</day>
<month>3</month>
<year>2016</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">
<month>4</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="epub">
<day>29</day>
<month>3</month>
<year>2016</year>
</pub-date>
<volume>45</volume>
<fpage>421</fpage>
<lpage>422</lpage>
<permissions>
<copyright-statement>Copyright © 2016 Published by Elsevier Ltd.</copyright-statement>
<copyright-year>2016</copyright-year>
<copyright-holder></copyright-holder>
<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>
</article-meta>
</front>
<body>
<p id="par0005">
<bold>Background</bold>
: The recently emerged Middle East syndrome coronavirus (MERS-CoV) can cause severe and fatal respiratory diseases in humans. Antibodies against MESR-CoV can be found in camels in the Middle East but also outside this regionThe high prevalence of circulating MERS-CoV neutralizing antibodies in dromedary camels from different geographic regions may indicate wide circulation of MERS-CoV in camels. The ongoing MERS-CoV outbreak in the Middle East and the lack of treatment options or licensed vaccines is of great concern. Vaccination of camels could potentially prevent the spread of this virus.</p>
<p id="par0010">
<bold>Methods & Materials</bold>
: We vaccinated 4 dromedary camels twice with a 4 week interval with10
<sup>8</sup>
PFU MVA-S via both nostrils and intramuscularly. Four control animals received non-recombinant MVA (n=2) or PBS (n=2). Three weeks post-boost, all animals were tested for presence specific antibody responses by MERS-CoV ELSA and virus neutralization assay (VNT). Next, all camels were challenged with a high dose of MERS-CoV and to study the pathological changes, two animals per groups were euthanized and necropsies were performed at day 4 and 14 pi. The antibody response, and pathology were analyses by MERS-CoV-S or MVA ELISAs, -VNTs, qRT-PCR, virus titration, immunohistochemistry (IHC) and
<italic>in situ</italic>
hybridization (ISH).</p>
<p id="par0015">
<bold>Results</bold>
: All vaccinated animal developed detectable serum neutralizing MERS-CoV or MVA specific antibody titers 3 weeks post boost vaccination. No clinical signs were observed in MVA-S vaccinated animals but mild clinical sign and a runny nose were observed in control-vaccinated animals after virus challenge. Interestingly, significant reduction of infectious virus excreted and viral RNA transcripts in the vaccinated animals nose after MERS-CoV challenge was observed as compared with control animals, and these protection correlated with presence of neutralizing antibody to MERS-CoV. In addition, in the nose of MVA-S vaccinated animals at day 4 pi, a few MERS-CoV infected cells were detected by IHC and ISH as compared with control camels. Interestingly, sera from MVA-S vaccinated animals cross neutralized camelpox virus.</p>
<p id="par0020">
<bold>Conclusion</bold>
: Our results demonstrate that vaccination of camels with MVA-S confers protects against MERS-CoV infection. In addition, induction of MVA specific antibody cross neutralize camelpox virus, suggesting that MVA-MERS-S can be used as a dual vaccine in dromedary camels.</p>
</body>
</pmc>
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