Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection.
Identifieur interne : 000079 ( PubMed/Checkpoint ); précédent : 000078; suivant : 000080Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection.
Auteurs : Kun Li [États-Unis] ; Zhuo Li [États-Unis] ; Christine Wohlford-Lenane [États-Unis] ; David K. Meyerholz [États-Unis] ; Rudragouda Channappanavar [États-Unis] ; Dong An [États-Unis] ; Stanley Perlman [États-Unis] ; Paul B. Mccray [États-Unis] ; Biao He [États-Unis]Source :
- mBio [ 2150-7511 ] ; 2020.
Descripteurs français
- KwdFr :
- Administration par voie nasale, Animaux, Anticorps antiviraux (sang), Glycoprotéine de spicule des coronavirus (génétique), Glycoprotéine de spicule des coronavirus (immunologie), Immunisation, Infections à coronavirus (), Infections à coronavirus (immunologie), Infections à coronavirus (mortalité), Modèles animaux de maladie humaine, Souris, Souris de lignée C57BL, Vaccins antiviraux (génétique), Vaccins antiviraux (immunologie), Vaccins synthétiques (administration et posologie), Vaccins synthétiques (génétique), Vaccins synthétiques (immunologie), Virus parainfluenza de type 5 (génétique).
- MESH :
- administration et posologie : Vaccins synthétiques.
- génétique : Glycoprotéine de spicule des coronavirus, Vaccins antiviraux, Vaccins synthétiques, Virus parainfluenza de type 5.
- immunologie : Glycoprotéine de spicule des coronavirus, Infections à coronavirus, Vaccins antiviraux, Vaccins synthétiques.
- mortalité : Infections à coronavirus.
- sang : Anticorps antiviraux.
- Administration par voie nasale, Animaux, Immunisation, Infections à coronavirus, Modèles animaux de maladie humaine, Souris, Souris de lignée C57BL.
English descriptors
- KwdEn :
- Administration, Intranasal, Animals, Antibodies, Viral (blood), Coronavirus Infections (immunology), Coronavirus Infections (mortality), Coronavirus Infections (prevention & control), Disease Models, Animal, Immunization, Mice, Mice, Inbred C57BL, Parainfluenza Virus 5 (genetics), Spike Glycoprotein, Coronavirus (genetics), Spike Glycoprotein, Coronavirus (immunology), Vaccines, Synthetic (administration & dosage), Vaccines, Synthetic (genetics), Vaccines, Synthetic (immunology), Viral Vaccines (genetics), Viral Vaccines (immunology).
- MESH :
- chemical , administration & dosage : Vaccines, Synthetic.
- chemical , blood : Antibodies, Viral.
- genetics : Parainfluenza Virus 5, Spike Glycoprotein, Coronavirus, Vaccines, Synthetic, Viral Vaccines.
- immunology : Coronavirus Infections, Spike Glycoprotein, Coronavirus, Vaccines, Synthetic, Viral Vaccines.
- mortality : Coronavirus Infections.
- prevention & control : Coronavirus Infections.
- Administration, Intranasal, Animals, Disease Models, Animal, Immunization, Mice, Mice, Inbred C57BL.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans and remains endemic in the Middle East since first being identified in 2012. There are currently no approved vaccines or therapies available for MERS-CoV. In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. A single intranasal administration of 104 PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERSMA6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 106 PFU UV-inactivated MERSMA6.1.2 mixed with Imject alum provided protection to only 25% of immunized mice. Intriguingly, an influx of eosinophils was observed only in the lungs of mice immunized with inactivated MERS-CoV, suggestive of a hypersensitivity-type response. Overall, our study indicated that PIV5-MERS-S is a promising effective vaccine candidate against MERS-CoV infection.IMPORTANCE MERS-CoV causes lethal infection in humans, and there is no vaccine. Our work demonstrates that PIV5 is a promising vector for developing a MERS vaccine. Furthermore, success of PIV5-based MERS vaccine can be employed to develop a vaccine for emerging CoVs such as SARS-CoV-2, which causes COVID-19.
DOI: 10.1128/mBio.00554-20
PubMed: 32265331
Affiliations:
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<front><div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans and remains endemic in the Middle East since first being identified in 2012. There are currently no approved vaccines or therapies available for MERS-CoV. In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. A single intranasal administration of 10<sup>4</sup>
PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERS<sub>MA</sub>
6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 10<sup>6</sup>
PFU UV-inactivated MERS<sub>MA</sub>
6.1.2 mixed with Imject alum provided protection to only 25% of immunized mice. Intriguingly, an influx of eosinophils was observed only in the lungs of mice immunized with inactivated MERS-CoV, suggestive of a hypersensitivity-type response. Overall, our study indicated that PIV5-MERS-S is a promising effective vaccine candidate against MERS-CoV infection.<b>IMPORTANCE</b>
MERS-CoV causes lethal infection in humans, and there is no vaccine. Our work demonstrates that PIV5 is a promising vector for developing a MERS vaccine. Furthermore, success of PIV5-based MERS vaccine can be employed to develop a vaccine for emerging CoVs such as SARS-CoV-2, which causes COVID-19.</div>
</front>
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<Abstract><AbstractText>Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans and remains endemic in the Middle East since first being identified in 2012. There are currently no approved vaccines or therapies available for MERS-CoV. In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. A single intranasal administration of 10<sup>4</sup>
PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERS<sub>MA</sub>
6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 10<sup>6</sup>
PFU UV-inactivated MERS<sub>MA</sub>
6.1.2 mixed with Imject alum provided protection to only 25% of immunized mice. Intriguingly, an influx of eosinophils was observed only in the lungs of mice immunized with inactivated MERS-CoV, suggestive of a hypersensitivity-type response. Overall, our study indicated that PIV5-MERS-S is a promising effective vaccine candidate against MERS-CoV infection.<b>IMPORTANCE</b>
MERS-CoV causes lethal infection in humans, and there is no vaccine. Our work demonstrates that PIV5 is a promising vector for developing a MERS vaccine. Furthermore, success of PIV5-based MERS vaccine can be employed to develop a vaccine for emerging CoVs such as SARS-CoV-2, which causes COVID-19.</AbstractText>
<CopyrightInformation>Copyright © 2020 Li et al.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Li</LastName>
<ForeName>Kun</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Department of Pediatrics, Pappajohn Biomedical Institute, University of Iowa, Iowa City, Iowa, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Li</LastName>
<ForeName>Zhuo</ForeName>
<Initials>Z</Initials>
<AffiliationInfo><Affiliation>Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wohlford-Lenane</LastName>
<ForeName>Christine</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Department of Pediatrics, Pappajohn Biomedical Institute, University of Iowa, Iowa City, Iowa, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Meyerholz</LastName>
<ForeName>David K</ForeName>
<Initials>DK</Initials>
<AffiliationInfo><Affiliation>Department of Pathology, University of Iowa, Iowa City, Iowa, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Channappanavar</LastName>
<ForeName>Rudragouda</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>An</LastName>
<ForeName>Dong</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Perlman</LastName>
<ForeName>Stanley</ForeName>
<Initials>S</Initials>
<Identifier Source="ORCID">0000-0003-4213-2354</Identifier>
<AffiliationInfo><Affiliation>Department of Pediatrics, Pappajohn Biomedical Institute, University of Iowa, Iowa City, Iowa, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>McCray</LastName>
<ForeName>Paul B</ForeName>
<Initials>PB</Initials>
<Suffix>Jr</Suffix>
<AffiliationInfo><Affiliation>Department of Pediatrics, Pappajohn Biomedical Institute, University of Iowa, Iowa City, Iowa, USA paul-mccray@uiowa.edu bhe@uga.edu.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>He</LastName>
<ForeName>Biao</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA paul-mccray@uiowa.edu bhe@uga.edu.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>P01 AI060699</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>P30 DK054759</GrantID>
<Acronym>DK</Acronym>
<Agency>NIDDK NIH HHS</Agency>
<Country>United States</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2020</Year>
<Month>04</Month>
<Day>07</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>mBio</MedlineTA>
<NlmUniqueID>101519231</NlmUniqueID>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000914">Antibodies, Viral</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D064370">Spike Glycoprotein, Coronavirus</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014614">Vaccines, Synthetic</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
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<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000281" MajorTopicYN="N">Administration, Intranasal</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000914" MajorTopicYN="N">Antibodies, Viral</DescriptorName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName>
<QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007114" MajorTopicYN="N">Immunization</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D045402" MajorTopicYN="N">Parainfluenza Virus 5</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D064370" MajorTopicYN="N">Spike Glycoprotein, Coronavirus</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014614" MajorTopicYN="N">Vaccines, Synthetic</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
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<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">COVID-19</Keyword>
<Keyword MajorTopicYN="Y">MERS</Keyword>
<Keyword MajorTopicYN="Y">coronavirus</Keyword>
<Keyword MajorTopicYN="Y">vaccine</Keyword>
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