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 : 000301 ( PubMed/Corpus ); précédent : 000300; suivant : 000302Single-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 ; Zhuo Li ; Christine Wohlford-Lenane ; David K. Meyerholz ; Rudragouda Channappanavar ; Dong An ; Stanley Perlman ; Paul B. Mccray ; Biao HeSource :
- mBio [ 2150-7511 ] ; 2020.
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
Links to Exploration step
pubmed:32265331Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">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.</title><author><name sortKey="Li, Kun" sort="Li, Kun" uniqKey="Li K" first="Kun" last="Li">Kun Li</name><affiliation><nlm:affiliation>Department of Pediatrics, Pappajohn Biomedical Institute, University of Iowa, Iowa City, Iowa, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Li, Zhuo" sort="Li, Zhuo" uniqKey="Li Z" first="Zhuo" last="Li">Zhuo Li</name><affiliation><nlm:affiliation>Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Wohlford Lenane, Christine" sort="Wohlford Lenane, Christine" uniqKey="Wohlford Lenane C" first="Christine" last="Wohlford-Lenane">Christine Wohlford-Lenane</name><affiliation><nlm:affiliation>Department of Pediatrics, Pappajohn Biomedical Institute, University of Iowa, Iowa City, Iowa, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Meyerholz, David K" sort="Meyerholz, David K" uniqKey="Meyerholz D" first="David K" last="Meyerholz">David K. Meyerholz</name><affiliation><nlm:affiliation>Department of Pathology, University of Iowa, Iowa City, Iowa, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Channappanavar, Rudragouda" sort="Channappanavar, Rudragouda" uniqKey="Channappanavar R" first="Rudragouda" last="Channappanavar">Rudragouda Channappanavar</name><affiliation><nlm:affiliation>Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA.</nlm:affiliation></affiliation></author><author><name sortKey="An, Dong" sort="An, Dong" uniqKey="An D" first="Dong" last="An">Dong An</name><affiliation><nlm:affiliation>Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><affiliation><nlm:affiliation>Department of Pediatrics, Pappajohn Biomedical Institute, University of Iowa, Iowa City, Iowa, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mccray, Paul B" sort="Mccray, Paul B" uniqKey="Mccray P" first="Paul B" last="Mccray">Paul B. 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Meyerholz</name><affiliation><nlm:affiliation>Department of Pathology, University of Iowa, Iowa City, Iowa, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Channappanavar, Rudragouda" sort="Channappanavar, Rudragouda" uniqKey="Channappanavar R" first="Rudragouda" last="Channappanavar">Rudragouda Channappanavar</name><affiliation><nlm:affiliation>Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA.</nlm:affiliation></affiliation></author><author><name sortKey="An, Dong" sort="An, Dong" uniqKey="An D" first="Dong" last="An">Dong An</name><affiliation><nlm:affiliation>Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><affiliation><nlm:affiliation>Department of Pediatrics, Pappajohn Biomedical Institute, University of Iowa, Iowa City, Iowa, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mccray, Paul B" sort="Mccray, Paul B" uniqKey="Mccray P" first="Paul B" last="Mccray">Paul B. Mccray</name><affiliation><nlm:affiliation>Department of Pediatrics, Pappajohn Biomedical Institute, University of Iowa, Iowa City, Iowa, USA paul-mccray@uiowa.edu bhe@uga.edu.</nlm:affiliation></affiliation></author><author><name sortKey="He, Biao" sort="He, Biao" uniqKey="He B" first="Biao" last="He">Biao He</name><affiliation><nlm:affiliation>Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA paul-mccray@uiowa.edu bhe@uga.edu.</nlm:affiliation></affiliation></author></analytic><series><title level="j">mBio</title><idno type="eISSN">2150-7511</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Administration, Intranasal</term><term>Animals</term><term>Antibodies, Viral (blood)</term><term>Coronavirus Infections (immunology)</term><term>Coronavirus Infections (mortality)</term><term>Coronavirus Infections (prevention & control)</term><term>Disease Models, Animal</term><term>Immunization</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Parainfluenza Virus 5 (genetics)</term><term>Spike Glycoprotein, Coronavirus (genetics)</term><term>Spike Glycoprotein, Coronavirus (immunology)</term><term>Vaccines, Synthetic (administration & dosage)</term><term>Vaccines, Synthetic (genetics)</term><term>Vaccines, Synthetic (immunology)</term><term>Viral Vaccines (genetics)</term><term>Viral Vaccines (immunology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Vaccines, Synthetic</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Parainfluenza Virus 5</term><term>Spike Glycoprotein, Coronavirus</term><term>Vaccines, Synthetic</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronavirus Infections</term><term>Spike Glycoprotein, Coronavirus</term><term>Vaccines, Synthetic</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Administration, Intranasal</term><term>Animals</term><term>Disease Models, Animal</term><term>Immunization</term><term>Mice</term><term>Mice, Inbred C57BL</term></keywords></textClass></profileDesc></teiHeader><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></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32265331</PMID><DateCompleted><Year>2020</Year><Month>04</Month><Day>10</Day></DateCompleted><DateRevised><Year>2020</Year><Month>04</Month><Day>17</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2150-7511</ISSN><JournalIssue CitedMedium="Internet"><Volume>11</Volume><Issue>2</Issue><PubDate><Year>2020</Year><Month>04</Month><Day>07</Day></PubDate></JournalIssue><Title>mBio</Title><ISOAbbreviation>mBio</ISOAbbreviation></Journal><ArticleTitle>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.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">e00554-20</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1128/mBio.00554-20</ELocationID><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><NameOfSubstance UI="D014765">Viral Vaccines</NameOfSubstance></Chemical></ChemicalList><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><MeshHeading><DescriptorName UI="D014765" MajorTopicYN="N">Viral Vaccines</DescriptorName><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 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