Immunogenicity of Different Forms of Middle East Respiratory Syndrome S Glycoprotein
Identifieur interne : 002202 ( Ncbi/Merge ); précédent : 002201; suivant : 002203Immunogenicity of Different Forms of Middle East Respiratory Syndrome S Glycoprotein
Auteurs : T. A. Ozharovskaia [Russie] ; O. V. Zubkova [Russie] ; I. V. Dolzhikova [Russie] ; A. S. Gromova [Russie] ; D. M. Grousova [Russie] ; A. I. Tukhvatulin [Russie] ; O. Popova [Russie] ; D. V. Shcheblyakov [Russie] ; D. N. Scherbinin [Russie] ; A. S. Dzharullaeva [Russie] ; A. S. Erokhova [Russie] ; M. M. Shmarov [Russie] ; S. Y. Loginova [Russie] ; S. V. Borisevich [Russie] ; B. S. Naroditsky [Russie] ; D. Y. Logunov [Russie] ; A. L. Gintsburg [Russie]Source :
- Acta Naturae [ 2075-8251 ] ; 2019.
Abstract
The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 during the first Middle East respiratory syndrome (MERS) outbreaks. MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality rate of ~35.5%. Currently, there are no registered vaccines or means of therapeutic protection against MERS in the world. The MERS-CoV S glycoprotein plays the most important role in the viral life cycle (virus internalization). The S protein is an immunodominant antigen and the main target for neutralizing antibodies. In the present study, the immunogenicities of five different forms of the MERS-CoV S glycoprotein were compared: the full-length S glycoprotein, the full-length S glycoprotein with the transmembrane domain of the G glycoprotein of VSV (S-G), the receptor-binding domain (RBD) of the S glycoprotein, the membrane-fused RBD (the RBD fused with the transmembrane domain of the VSV G glycoprotein (RBD-G)), and the RBD fused with Fc of human IgG1 (RBD-Fc). Recombinant vectors based on human adenoviruses type 5 (rAd5) were used as delivery vehicles. Vaccination with all of the developed rAd5 vectors elicited a balanced Th1/Th2 response in mice. The most robust humoral immune response was induced after the animal had been vaccinated with the membrane-fused RBD (rAd5-RBD-G). Only immunization with membrane forms of the glycoprotein (rAd5-S, rAd5-S-G, and rAd5-RBD-G) elicited neutralizing antibodies among all vaccinated animals. The most significant cellular immune response was induced after vaccination of the animals with the full-length S (rAd5-S). These investigations suggest that the full-length S and the membrane form of the RBD (RBD-G) are the most promising vaccine candidates among all the studied forms of S glycoprotein.
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PubMed: 31024747
PubMed Central: 6475872
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<affiliation wicri:level="3"><nlm:aff id="AF1">Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia</nlm:aff>
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<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Erokhova, A S" sort="Erokhova, A S" uniqKey="Erokhova A" first="A. S." last="Erokhova">A. S. Erokhova</name>
<affiliation wicri:level="3"><nlm:aff id="AF1">Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shmarov, M M" sort="Shmarov, M M" uniqKey="Shmarov M" first="M. M." last="Shmarov">M. M. Shmarov</name>
<affiliation wicri:level="3"><nlm:aff id="AF1">Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Loginova, S Y" sort="Loginova, S Y" uniqKey="Loginova S" first="S. Y." last="Loginova">S. Y. Loginova</name>
<affiliation wicri:level="1"><nlm:aff id="AF2">«48 Central Research Institute», Ministry of Defense of Russian Federation, Oktyabrskaya Str. 11, 141306 , Sergiev Posad, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>«48 Central Research Institute», Ministry of Defense of Russian Federation, Oktyabrskaya Str. 11, 141306 , Sergiev Posad</wicri:regionArea>
<wicri:noRegion>Sergiev Posad</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Borisevich, S V" sort="Borisevich, S V" uniqKey="Borisevich S" first="S. V." last="Borisevich">S. V. Borisevich</name>
<affiliation wicri:level="1"><nlm:aff id="AF2">«48 Central Research Institute», Ministry of Defense of Russian Federation, Oktyabrskaya Str. 11, 141306 , Sergiev Posad, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>«48 Central Research Institute», Ministry of Defense of Russian Federation, Oktyabrskaya Str. 11, 141306 , Sergiev Posad</wicri:regionArea>
<wicri:noRegion>Sergiev Posad</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Naroditsky, B S" sort="Naroditsky, B S" uniqKey="Naroditsky B" first="B. S." last="Naroditsky">B. S. Naroditsky</name>
<affiliation wicri:level="3"><nlm:aff id="AF1">Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Logunov, D Y" sort="Logunov, D Y" uniqKey="Logunov D" first="D. Y." last="Logunov">D. Y. Logunov</name>
<affiliation wicri:level="3"><nlm:aff id="AF1">Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gintsburg, A L" sort="Gintsburg, A L" uniqKey="Gintsburg A" first="A. L." last="Gintsburg">A. L. Gintsburg</name>
<affiliation wicri:level="3"><nlm:aff id="AF1">Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Acta Naturae</title>
<idno type="ISSN">2075-8251</idno>
<imprint><date when="2019">2019</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
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<front><div type="abstract" xml:lang="en"><p>The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in
2012 during the first Middle East respiratory syndrome (MERS) outbreaks.
MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality
rate of ~35.5%. Currently, there are no registered vaccines or means of
therapeutic protection against MERS in the world. The MERS-CoV S glycoprotein
plays the most important role in the viral life cycle (virus internalization).
The S protein is an immunodominant antigen and the main target for neutralizing
antibodies. In the present study, the immunogenicities of five different forms
of the MERS-CoV S glycoprotein were compared: the full-length S glycoprotein,
the full-length S glycoprotein with the transmembrane domain of the G
glycoprotein of VSV (S-G), the receptor-binding domain (RBD) of the S
glycoprotein, the membrane-fused RBD (the RBD fused with the transmembrane
domain of the VSV G glycoprotein (RBD-G)), and the RBD fused with Fc of human
IgG1 (RBD-Fc). Recombinant vectors based on human adenoviruses type 5 (rAd5)
were used as delivery vehicles. Vaccination with all of the developed rAd5
vectors elicited a balanced Th1/Th2 response in mice. The most robust humoral
immune response was induced after the animal had been vaccinated with the
membrane-fused RBD (rAd5-RBD-G). Only immunization with membrane forms of the
glycoprotein (rAd5-S, rAd5-S-G, and rAd5-RBD-G) elicited neutralizing
antibodies among all vaccinated animals. The most significant cellular immune
response was induced after vaccination of the animals with the full-length S
(rAd5-S). These investigations suggest that the full-length S and the membrane
form of the RBD (RBD-G) are the most promising vaccine candidates among all the
studied forms of S glycoprotein.
</p>
</div>
</front>
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<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
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</author>
<author><name sortKey="Dolzhikova, I V" sort="Dolzhikova, I V" uniqKey="Dolzhikova I" first="I. V." last="Dolzhikova">I. V. Dolzhikova</name>
<affiliation wicri:level="3"><nlm:aff id="AF1">Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gromova, A S" sort="Gromova, A S" uniqKey="Gromova A" first="A. S." last="Gromova">A. S. Gromova</name>
<affiliation wicri:level="3"><nlm:aff id="AF1">Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Grousova, D M" sort="Grousova, D M" uniqKey="Grousova D" first="D. M." last="Grousova">D. M. Grousova</name>
<affiliation wicri:level="3"><nlm:aff id="AF1">Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tukhvatulin, A I" sort="Tukhvatulin, A I" uniqKey="Tukhvatulin A" first="A. I." last="Tukhvatulin">A. I. Tukhvatulin</name>
<affiliation wicri:level="3"><nlm:aff id="AF1">Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Popova, O" sort="Popova, O" uniqKey="Popova O" first="O." last="Popova">O. Popova</name>
<affiliation wicri:level="3"><nlm:aff id="AF1">Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shcheblyakov, D V" sort="Shcheblyakov, D V" uniqKey="Shcheblyakov D" first="D. V." last="Shcheblyakov">D. V. Shcheblyakov</name>
<affiliation wicri:level="3"><nlm:aff id="AF1">Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Scherbinin, D N" sort="Scherbinin, D N" uniqKey="Scherbinin D" first="D. N." last="Scherbinin">D. N. Scherbinin</name>
<affiliation wicri:level="3"><nlm:aff id="AF1">Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dzharullaeva, A S" sort="Dzharullaeva, A S" uniqKey="Dzharullaeva A" first="A. S." last="Dzharullaeva">A. S. Dzharullaeva</name>
<affiliation wicri:level="3"><nlm:aff id="AF1">Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Erokhova, A S" sort="Erokhova, A S" uniqKey="Erokhova A" first="A. S." last="Erokhova">A. S. Erokhova</name>
<affiliation wicri:level="3"><nlm:aff id="AF1">Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shmarov, M M" sort="Shmarov, M M" uniqKey="Shmarov M" first="M. M." last="Shmarov">M. M. Shmarov</name>
<affiliation wicri:level="3"><nlm:aff id="AF1">Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Loginova, S Y" sort="Loginova, S Y" uniqKey="Loginova S" first="S. Y." last="Loginova">S. Y. Loginova</name>
<affiliation wicri:level="1"><nlm:aff id="AF2">«48 Central Research Institute», Ministry of Defense of Russian Federation, Oktyabrskaya Str. 11, 141306 , Sergiev Posad, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>«48 Central Research Institute», Ministry of Defense of Russian Federation, Oktyabrskaya Str. 11, 141306 , Sergiev Posad</wicri:regionArea>
<wicri:noRegion>Sergiev Posad</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Borisevich, S V" sort="Borisevich, S V" uniqKey="Borisevich S" first="S. V." last="Borisevich">S. V. Borisevich</name>
<affiliation wicri:level="1"><nlm:aff id="AF2">«48 Central Research Institute», Ministry of Defense of Russian Federation, Oktyabrskaya Str. 11, 141306 , Sergiev Posad, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>«48 Central Research Institute», Ministry of Defense of Russian Federation, Oktyabrskaya Str. 11, 141306 , Sergiev Posad</wicri:regionArea>
<wicri:noRegion>Sergiev Posad</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Naroditsky, B S" sort="Naroditsky, B S" uniqKey="Naroditsky B" first="B. S." last="Naroditsky">B. S. Naroditsky</name>
<affiliation wicri:level="3"><nlm:aff id="AF1">Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Logunov, D Y" sort="Logunov, D Y" uniqKey="Logunov D" first="D. Y." last="Logunov">D. Y. Logunov</name>
<affiliation wicri:level="3"><nlm:aff id="AF1">Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gintsburg, A L" sort="Gintsburg, A L" uniqKey="Gintsburg A" first="A. L." last="Gintsburg">A. L. Gintsburg</name>
<affiliation wicri:level="3"><nlm:aff id="AF1">Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Acta Naturae</title>
<idno type="ISSN">2075-8251</idno>
<imprint><date when="2019">2019</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
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<front><div type="abstract" xml:lang="en"><p>The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in
2012 during the first Middle East respiratory syndrome (MERS) outbreaks.
MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality
rate of ~35.5%. Currently, there are no registered vaccines or means of
therapeutic protection against MERS in the world. The MERS-CoV S glycoprotein
plays the most important role in the viral life cycle (virus internalization).
The S protein is an immunodominant antigen and the main target for neutralizing
antibodies. In the present study, the immunogenicities of five different forms
of the MERS-CoV S glycoprotein were compared: the full-length S glycoprotein,
the full-length S glycoprotein with the transmembrane domain of the G
glycoprotein of VSV (S-G), the receptor-binding domain (RBD) of the S
glycoprotein, the membrane-fused RBD (the RBD fused with the transmembrane
domain of the VSV G glycoprotein (RBD-G)), and the RBD fused with Fc of human
IgG1 (RBD-Fc). Recombinant vectors based on human adenoviruses type 5 (rAd5)
were used as delivery vehicles. Vaccination with all of the developed rAd5
vectors elicited a balanced Th1/Th2 response in mice. The most robust humoral
immune response was induced after the animal had been vaccinated with the
membrane-fused RBD (rAd5-RBD-G). Only immunization with membrane forms of the
glycoprotein (rAd5-S, rAd5-S-G, and rAd5-RBD-G) elicited neutralizing
antibodies among all vaccinated animals. The most significant cellular immune
response was induced after vaccination of the animals with the full-length S
(rAd5-S). These investigations suggest that the full-length S and the membrane
form of the RBD (RBD-G) are the most promising vaccine candidates among all the
studied forms of S glycoprotein.
</p>
</div>
</front>
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<country xml:lang="fr">Russie</country>
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<country xml:lang="fr">Russie</country>
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<country xml:lang="fr">Russie</country>
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<author><name sortKey="Loginova, S Y" sort="Loginova, S Y" uniqKey="Loginova S" first="S Y" last="Loginova">S Y Loginova</name>
<affiliation wicri:level="1"><nlm:affiliation>«48 Central Research Institute», Ministry of Defense of Russian Federation, Oktyabrskaya Str. 11, 141306 , Sergiev Posad, Russia.</nlm:affiliation>
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<author><name sortKey="Borisevich, S V" sort="Borisevich, S V" uniqKey="Borisevich S" first="S V" last="Borisevich">S V Borisevich</name>
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<country xml:lang="fr">Russie</country>
<wicri:regionArea>«48 Central Research Institute», Ministry of Defense of Russian Federation, Oktyabrskaya Str. 11, 141306 , Sergiev Posad</wicri:regionArea>
<wicri:noRegion>Sergiev Posad</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Naroditsky, B S" sort="Naroditsky, B S" uniqKey="Naroditsky B" first="B S" last="Naroditsky">B S Naroditsky</name>
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<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Logunov, D Y" sort="Logunov, D Y" uniqKey="Logunov D" first="D Y" last="Logunov">D Y Logunov</name>
<affiliation wicri:level="3"><nlm:affiliation>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gintsburg, A L" sort="Gintsburg, A L" uniqKey="Gintsburg A" first="A L" last="Gintsburg">A L Gintsburg</name>
<affiliation wicri:level="3"><nlm:affiliation>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
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<publicationStmt><idno type="wicri:source">PubMed</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Immunogenicity of Different Forms of Middle East Respiratory Syndrome S Glycoprotein.</title>
<author><name sortKey="Ozharovskaia, T A" sort="Ozharovskaia, T A" uniqKey="Ozharovskaia T" first="T A" last="Ozharovskaia">T A Ozharovskaia</name>
<affiliation wicri:level="3"><nlm:affiliation>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zubkova, O V" sort="Zubkova, O V" uniqKey="Zubkova O" first="O V" last="Zubkova">O V Zubkova</name>
<affiliation wicri:level="3"><nlm:affiliation>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dolzhikova, I V" sort="Dolzhikova, I V" uniqKey="Dolzhikova I" first="I V" last="Dolzhikova">I V Dolzhikova</name>
<affiliation wicri:level="3"><nlm:affiliation>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gromova, A S" sort="Gromova, A S" uniqKey="Gromova A" first="A S" last="Gromova">A S Gromova</name>
<affiliation wicri:level="3"><nlm:affiliation>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Grousova, D M" sort="Grousova, D M" uniqKey="Grousova D" first="D M" last="Grousova">D M Grousova</name>
<affiliation wicri:level="3"><nlm:affiliation>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tukhvatulin, A I" sort="Tukhvatulin, A I" uniqKey="Tukhvatulin A" first="A I" last="Tukhvatulin">A I Tukhvatulin</name>
<affiliation wicri:level="3"><nlm:affiliation>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Popova, O" sort="Popova, O" uniqKey="Popova O" first="O" last="Popova">O. Popova</name>
<affiliation wicri:level="3"><nlm:affiliation>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shcheblyakov, D V" sort="Shcheblyakov, D V" uniqKey="Shcheblyakov D" first="D V" last="Shcheblyakov">D V Shcheblyakov</name>
<affiliation wicri:level="3"><nlm:affiliation>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Scherbinin, D N" sort="Scherbinin, D N" uniqKey="Scherbinin D" first="D N" last="Scherbinin">D N Scherbinin</name>
<affiliation wicri:level="3"><nlm:affiliation>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dzharullaeva, A S" sort="Dzharullaeva, A S" uniqKey="Dzharullaeva A" first="A S" last="Dzharullaeva">A S Dzharullaeva</name>
<affiliation wicri:level="3"><nlm:affiliation>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Erokhova, A S" sort="Erokhova, A S" uniqKey="Erokhova A" first="A S" last="Erokhova">A S Erokhova</name>
<affiliation wicri:level="3"><nlm:affiliation>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shmarov, M M" sort="Shmarov, M M" uniqKey="Shmarov M" first="M M" last="Shmarov">M M Shmarov</name>
<affiliation wicri:level="3"><nlm:affiliation>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Loginova, S Y" sort="Loginova, S Y" uniqKey="Loginova S" first="S Y" last="Loginova">S Y Loginova</name>
<affiliation wicri:level="1"><nlm:affiliation>«48 Central Research Institute», Ministry of Defense of Russian Federation, Oktyabrskaya Str. 11, 141306 , Sergiev Posad, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>«48 Central Research Institute», Ministry of Defense of Russian Federation, Oktyabrskaya Str. 11, 141306 , Sergiev Posad</wicri:regionArea>
<wicri:noRegion>Sergiev Posad</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Borisevich, S V" sort="Borisevich, S V" uniqKey="Borisevich S" first="S V" last="Borisevich">S V Borisevich</name>
<affiliation wicri:level="1"><nlm:affiliation>«48 Central Research Institute», Ministry of Defense of Russian Federation, Oktyabrskaya Str. 11, 141306 , Sergiev Posad, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>«48 Central Research Institute», Ministry of Defense of Russian Federation, Oktyabrskaya Str. 11, 141306 , Sergiev Posad</wicri:regionArea>
<wicri:noRegion>Sergiev Posad</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Naroditsky, B S" sort="Naroditsky, B S" uniqKey="Naroditsky B" first="B S" last="Naroditsky">B S Naroditsky</name>
<affiliation wicri:level="3"><nlm:affiliation>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Logunov, D Y" sort="Logunov, D Y" uniqKey="Logunov D" first="D Y" last="Logunov">D Y Logunov</name>
<affiliation wicri:level="3"><nlm:affiliation>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gintsburg, A L" sort="Gintsburg, A L" uniqKey="Gintsburg A" first="A L" last="Gintsburg">A L Gintsburg</name>
<affiliation wicri:level="3"><nlm:affiliation>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health of Russian Federation, Gamaleya Str. 18, 123098, Moscow</wicri:regionArea>
<placeName><settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Acta naturae</title>
<idno type="ISSN">2075-8251</idno>
</series>
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<front><div type="abstract" xml:lang="en">The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 during the first Middle East respiratory syndrome (MERS) outbreaks. MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality rate of ~35.5%. Currently, there are no registered vaccines or means of therapeutic protection against MERS in the world. The MERS-CoV S glycoprotein plays the most important role in the viral life cycle (virus internalization). The S protein is an immunodominant antigen and the main target for neutralizing antibodies. In the present study, the immunogenicities of five different forms of the MERS-CoV S glycoprotein were compared: the full-length S glycoprotein, the full-length S glycoprotein with the transmembrane domain of the G glycoprotein of VSV (S-G), the receptor-binding domain (RBD) of the S glycoprotein, the membrane-fused RBD (the RBD fused with the transmembrane domain of the VSV G glycoprotein (RBD-G)), and the RBD fused with Fc of human IgG1 (RBD-Fc). Recombinant vectors based on human adenoviruses type 5 (rAd5) were used as delivery vehicles. Vaccination with all of the developed rAd5 vectors elicited a balanced Th1/Th2 response in mice. The most robust humoral immune response was induced after the animal had been vaccinated with the membrane-fused RBD (rAd5-RBD-G). Only immunization with membrane forms of the glycoprotein (rAd5-S, rAd5-S-G, and rAd5-RBD-G) elicited neutralizing antibodies among all vaccinated animals. The most significant cellular immune response was induced after vaccination of the animals with the full-length S (rAd5-S). These investigations suggest that the full-length S and the membrane form of the RBD (RBD-G) are the most promising vaccine candidates among all the studied forms of S glycoprotein.</div>
</front>
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