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Heterologous prime-boost vaccination with adenoviral vector and protein nanoparticles induces both Th1 and Th2 responses against Middle East respiratory syndrome coronavirus.

Identifieur interne : 000910 ( PubMed/Curation ); précédent : 000909; suivant : 000911

Heterologous prime-boost vaccination with adenoviral vector and protein nanoparticles induces both Th1 and Th2 responses against Middle East respiratory syndrome coronavirus.

Auteurs : Seo-Yeon Jung [Corée du Sud] ; Kyung Won Kang [Corée du Sud] ; Eun-Young Lee [Corée du Sud] ; Dong-Won Seo [Corée du Sud] ; Hong-Lim Kim [Corée du Sud] ; Hak Kim [Corée du Sud] ; Taewoo Kwon [Corée du Sud] ; Hye-Lim Park [Corée du Sud] ; Hun Kim [Corée du Sud] ; Sang-Myeong Lee [Corée du Sud] ; Jae-Hwan Nam [Corée du Sud]

Source :

RBID : pubmed:29739720

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English descriptors

Abstract

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic and zoonotic virus with a fatality rate in humans of over 35%. Although several vaccine candidates have been developed, there is still no clinically available vaccine for MERS-CoV. In this study, we developed two types of MERS-CoV vaccines: a recombinant adenovirus serotype 5 encoding the MERS-CoV spike gene (Ad5/MERS) and spike protein nanoparticles formulated with aluminum (alum) adjuvant. Next, we tested a heterologous prime-boost vaccine strategy, which compared priming with Ad5/MERS and boosting with spike protein nanoparticles and vice versa, with homologous prime-boost vaccination comprising priming and boosting with either spike protein nanoparticles or Ad5/MERS. Although both types of vaccine could induce specific immunoglobulin G against MERS-CoV, neutralizing antibodies against MERS-CoV were induced only by heterologous prime-boost immunization and homologous immunization with spike protein nanoparticles. Interestingly, Th1 cell activation was induced by immunization schedules including Ad5/MERS, but not by those including only spike protein nanoparticles. Heterologous prime-boost vaccination regimens including Ad5/MERS elicited simultaneous Th1 and Th2 responses, but homologous prime-boost regimens did not. Thus, heterologous prime-boost may induce longer-lasting immune responses against MERS-CoV because of an appropriate balance of Th1/Th2 responses. However, both heterologous prime-boost and homologous spike protein nanoparticles vaccinations could provide protection from MERS-CoV challenge in mice. Our results demonstrate that heterologous immunization by priming with Ad5/MERS and boosting with spike protein nanoparticles could be an efficient prophylactic strategy against MERS-CoV infection.

DOI: 10.1016/j.vaccine.2018.04.082
PubMed: 29739720

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<term>Adenoviruses, Human (immunology)</term>
<term>Adjuvants, Immunologic (administration & dosage)</term>
<term>Alum Compounds (administration & dosage)</term>
<term>Animals</term>
<term>Antibodies, Neutralizing (biosynthesis)</term>
<term>Antibodies, Viral (biosynthesis)</term>
<term>Coronavirus Infections (immunology)</term>
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<term>Middle East Respiratory Syndrome Coronavirus (immunology)</term>
<term>Nanoparticles (administration & dosage)</term>
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<term>Viral Vaccines</term>
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<term>Coronavirus Infections</term>
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<term>Infections à coronavirus</term>
<term>Lymphocytes auxiliaires Th1</term>
<term>Lymphocytes auxiliaires Th2</term>
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<term>Female</term>
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<term>Animaux</term>
<term>Calendrier vaccinal</term>
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<term>Femelle</term>
<term>Humains</term>
<term>Immunogénicité des vaccins</term>
<term>Infections à coronavirus</term>
<term>Lymphocytes auxiliaires Th1</term>
<term>Lymphocytes auxiliaires Th2</term>
<term>Nanoparticules</term>
<term>Rappel de vaccin</term>
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<term>Souris de lignée BALB C</term>
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<div type="abstract" xml:lang="en">The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic and zoonotic virus with a fatality rate in humans of over 35%. Although several vaccine candidates have been developed, there is still no clinically available vaccine for MERS-CoV. In this study, we developed two types of MERS-CoV vaccines: a recombinant adenovirus serotype 5 encoding the MERS-CoV spike gene (Ad5/MERS) and spike protein nanoparticles formulated with aluminum (alum) adjuvant. Next, we tested a heterologous prime-boost vaccine strategy, which compared priming with Ad5/MERS and boosting with spike protein nanoparticles and vice versa, with homologous prime-boost vaccination comprising priming and boosting with either spike protein nanoparticles or Ad5/MERS. Although both types of vaccine could induce specific immunoglobulin G against MERS-CoV, neutralizing antibodies against MERS-CoV were induced only by heterologous prime-boost immunization and homologous immunization with spike protein nanoparticles. Interestingly, Th1 cell activation was induced by immunization schedules including Ad5/MERS, but not by those including only spike protein nanoparticles. Heterologous prime-boost vaccination regimens including Ad5/MERS elicited simultaneous Th1 and Th2 responses, but homologous prime-boost regimens did not. Thus, heterologous prime-boost may induce longer-lasting immune responses against MERS-CoV because of an appropriate balance of Th1/Th2 responses. However, both heterologous prime-boost and homologous spike protein nanoparticles vaccinations could provide protection from MERS-CoV challenge in mice. Our results demonstrate that heterologous immunization by priming with Ad5/MERS and boosting with spike protein nanoparticles could be an efficient prophylactic strategy against MERS-CoV infection.</div>
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<Issue>24</Issue>
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<Year>2018</Year>
<Month>06</Month>
<Day>07</Day>
</PubDate>
</JournalIssue>
<Title>Vaccine</Title>
<ISOAbbreviation>Vaccine</ISOAbbreviation>
</Journal>
<ArticleTitle>Heterologous prime-boost vaccination with adenoviral vector and protein nanoparticles induces both Th1 and Th2 responses against Middle East respiratory syndrome coronavirus.</ArticleTitle>
<Pagination>
<MedlinePgn>3468-3476</MedlinePgn>
</Pagination>
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<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.vaccine.2018.04.082</ELocationID>
<Abstract>
<AbstractText>The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic and zoonotic virus with a fatality rate in humans of over 35%. Although several vaccine candidates have been developed, there is still no clinically available vaccine for MERS-CoV. In this study, we developed two types of MERS-CoV vaccines: a recombinant adenovirus serotype 5 encoding the MERS-CoV spike gene (Ad5/MERS) and spike protein nanoparticles formulated with aluminum (alum) adjuvant. Next, we tested a heterologous prime-boost vaccine strategy, which compared priming with Ad5/MERS and boosting with spike protein nanoparticles and vice versa, with homologous prime-boost vaccination comprising priming and boosting with either spike protein nanoparticles or Ad5/MERS. Although both types of vaccine could induce specific immunoglobulin G against MERS-CoV, neutralizing antibodies against MERS-CoV were induced only by heterologous prime-boost immunization and homologous immunization with spike protein nanoparticles. Interestingly, Th1 cell activation was induced by immunization schedules including Ad5/MERS, but not by those including only spike protein nanoparticles. Heterologous prime-boost vaccination regimens including Ad5/MERS elicited simultaneous Th1 and Th2 responses, but homologous prime-boost regimens did not. Thus, heterologous prime-boost may induce longer-lasting immune responses against MERS-CoV because of an appropriate balance of Th1/Th2 responses. However, both heterologous prime-boost and homologous spike protein nanoparticles vaccinations could provide protection from MERS-CoV challenge in mice. Our results demonstrate that heterologous immunization by priming with Ad5/MERS and boosting with spike protein nanoparticles could be an efficient prophylactic strategy against MERS-CoV infection.</AbstractText>
<CopyrightInformation>Copyright © 2018 Elsevier Ltd. All rights reserved.</CopyrightInformation>
</Abstract>
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<Author ValidYN="Y">
<LastName>Jung</LastName>
<ForeName>Seo-Yeon</ForeName>
<Initials>SY</Initials>
<AffiliationInfo>
<Affiliation>Department of Biotechnology, The Catholic University of Korea, Bucheon 14662, Republic of Korea.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y">
<LastName>Kang</LastName>
<ForeName>Kyung Won</ForeName>
<Initials>KW</Initials>
<AffiliationInfo>
<Affiliation>Division of Biotechnology, Chonbuk National University, Iksan 570-752, Republic of Korea.</Affiliation>
</AffiliationInfo>
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<LastName>Lee</LastName>
<ForeName>Eun-Young</ForeName>
<Initials>EY</Initials>
<AffiliationInfo>
<Affiliation>Department of Biotechnology, The Catholic University of Korea, Bucheon 14662, Republic of Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Seo</LastName>
<ForeName>Dong-Won</ForeName>
<Initials>DW</Initials>
<AffiliationInfo>
<Affiliation>Division of Biotechnology, Chonbuk National University, Iksan 570-752, Republic of Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Kim</LastName>
<ForeName>Hong-Lim</ForeName>
<Initials>HL</Initials>
<AffiliationInfo>
<Affiliation>Seoul St. Mary's Hospital, School of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Kim</LastName>
<ForeName>Hak</ForeName>
<Initials>H</Initials>
<AffiliationInfo>
<Affiliation>Division of VAX R&D, Life Science Research Institute, SK Chemical, Seongnam 12771, Republic of Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Kwon</LastName>
<ForeName>TaeWoo</ForeName>
<Initials>T</Initials>
<AffiliationInfo>
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</AffiliationInfo>
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<LastName>Park</LastName>
<ForeName>Hye-Lim</ForeName>
<Initials>HL</Initials>
<AffiliationInfo>
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</AffiliationInfo>
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<ForeName>Hun</ForeName>
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<AffiliationInfo>
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</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Lee</LastName>
<ForeName>Sang-Myeong</ForeName>
<Initials>SM</Initials>
<AffiliationInfo>
<Affiliation>Division of Biotechnology, Chonbuk National University, Iksan 570-752, Republic of Korea. Electronic address: leesangm@jbnu.ac.kr.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Nam</LastName>
<ForeName>Jae-Hwan</ForeName>
<Initials>JH</Initials>
<AffiliationInfo>
<Affiliation>Department of Biotechnology, The Catholic University of Korea, Bucheon 14662, Republic of Korea. Electronic address: jhnam@catholic.ac.kr.</Affiliation>
</AffiliationInfo>
</Author>
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<Language>eng</Language>
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<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
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<Year>2018</Year>
<Month>05</Month>
<Day>05</Day>
</ArticleDate>
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<Country>Netherlands</Country>
<MedlineTA>Vaccine</MedlineTA>
<NlmUniqueID>8406899</NlmUniqueID>
<ISSNLinking>0264-410X</ISSNLinking>
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<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000276">Adjuvants, Immunologic</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000534">Alum Compounds</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D057134">Antibodies, Neutralizing</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000914">Antibodies, Viral</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D007074">Immunoglobulin G</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D064370">Spike Glycoprotein, Coronavirus</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014765">Viral Vaccines</NameOfSubstance>
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</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList>
<MeshHeading>
<DescriptorName UI="D000260" MajorTopicYN="N">Adenoviruses, Human</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000276" MajorTopicYN="N">Adjuvants, Immunologic</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000534" MajorTopicYN="N">Alum Compounds</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D057134" MajorTopicYN="N">Antibodies, Neutralizing</DescriptorName>
<QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000914" MajorTopicYN="N">Antibodies, Viral</DescriptorName>
<QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</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>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D007115" MajorTopicYN="N">Immunization Schedule</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D007117" MajorTopicYN="N">Immunization, Secondary</DescriptorName>
<QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000071497" MajorTopicYN="N">Immunogenicity, Vaccine</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D007074" MajorTopicYN="N">Immunoglobulin G</DescriptorName>
<QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D008213" MajorTopicYN="N">Lymphocyte Activation</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D008807" MajorTopicYN="N">Mice, Inbred BALB C</DescriptorName>
</MeshHeading>
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<DescriptorName UI="D065207" MajorTopicYN="N">Middle East Respiratory Syndrome Coronavirus</DescriptorName>
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<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
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<MeshHeading>
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<QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
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<DescriptorName UI="D064370" MajorTopicYN="N">Spike Glycoprotein, Coronavirus</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D018417" MajorTopicYN="N">Th1 Cells</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
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<DescriptorName UI="D018418" MajorTopicYN="N">Th2 Cells</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
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<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
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<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
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<Keyword MajorTopicYN="Y">Adenovirus 5</Keyword>
<Keyword MajorTopicYN="Y">Heterologous prime–boost</Keyword>
<Keyword MajorTopicYN="Y">MERS-CoV</Keyword>
<Keyword MajorTopicYN="Y">Th1</Keyword>
<Keyword MajorTopicYN="Y">Th2</Keyword>
<Keyword MajorTopicYN="Y">Vaccine</Keyword>
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