A Novel Bacterium-Like Particle Vaccine Displaying the MERS-CoV Receptor-Binding Domain Induces Specific Mucosal and Systemic Immune Responses in Mice.
Identifieur interne : 000705 ( PubMed/Checkpoint ); précédent : 000704; suivant : 000706A Novel Bacterium-Like Particle Vaccine Displaying the MERS-CoV Receptor-Binding Domain Induces Specific Mucosal and Systemic Immune Responses in Mice.
Auteurs : Entao Li [République populaire de Chine] ; Hang Chi [République populaire de Chine] ; Pei Huang [République populaire de Chine] ; Feihu Yan [République populaire de Chine] ; Ying Zhang [République populaire de Chine] ; Chuanyu Liu [République populaire de Chine] ; Zhenshan Wang [République populaire de Chine] ; Guohua Li [République populaire de Chine] ; Shengnan Zhang [République populaire de Chine] ; Ruo Mo [République populaire de Chine] ; Hongli Jin [République populaire de Chine] ; Hualei Wang [République populaire de Chine] ; Na Feng [République populaire de Chine] ; Jianzhong Wang [République populaire de Chine] ; Yuhai Bi [République populaire de Chine] ; Tiecheng Wang [République populaire de Chine] ; Weiyang Sun [République populaire de Chine] ; Yuwei Gao [République populaire de Chine] ; Yongkun Zhao [République populaire de Chine] ; Songtao Yang [République populaire de Chine] ; Xianzhu Xia [République populaire de Chine]Source :
- Viruses [ 1999-4915 ] ; 2019.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV), a new coronavirus that has been causing severe and fatal acute respiratory illnesses in humans since its outbreak in 2012, has raised public fear worldwide. The development of prophylactics and therapeutics is urgently needed to prevent and control MERS-CoV infections. In this study, a bacterium (Lactococcus lactis)-like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). The designs included different numbers of lysin motif (LysM) repeats in the PAs linked by linkers (RBD-linker-PA2 (RLP2), RBD-linker-PA3 (RLP3) and RBD-PA3 (RP3)), and three LysM repeats and a linker in the fusion proteins increased the binding activity to the RBD. The specific immune responses were tested by intranasally immunizing mice with RLP3-GEM with or without the adjuvant GEL01. The results showed that GEL01-adjuvanted RLP3-GEM increased the systemic humoral, cellular and local mucosal immune responses in the mouse model, especially in the intestinal tract. The above results indicate that the MERS-CoV BLP product has the potential to be developed into a promising mucosal candidate vaccine to protect against MERS-CoV infections.
DOI: 10.3390/v11090799
PubMed: 31470645
Affiliations:
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<author><name sortKey="Yang, Songtao" sort="Yang, Songtao" uniqKey="Yang S" first="Songtao" last="Yang">Songtao Yang</name>
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<author><name sortKey="Xia, Xianzhu" sort="Xia, Xianzhu" uniqKey="Xia X" first="Xianzhu" last="Xia">Xianzhu Xia</name>
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<author><name sortKey="Zhang, Ying" sort="Zhang, Ying" uniqKey="Zhang Y" first="Ying" last="Zhang">Ying Zhang</name>
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<author><name sortKey="Liu, Chuanyu" sort="Liu, Chuanyu" uniqKey="Liu C" first="Chuanyu" last="Liu">Chuanyu Liu</name>
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<author><name sortKey="Wang, Zhenshan" sort="Wang, Zhenshan" uniqKey="Wang Z" first="Zhenshan" last="Wang">Zhenshan Wang</name>
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<author><name sortKey="Li, Guohua" sort="Li, Guohua" uniqKey="Li G" first="Guohua" last="Li">Guohua Li</name>
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<wicri:regionArea>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000</wicri:regionArea>
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<author><name sortKey="Zhang, Shengnan" sort="Zhang, Shengnan" uniqKey="Zhang S" first="Shengnan" last="Zhang">Shengnan Zhang</name>
<affiliation wicri:level="1"><nlm:affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000</wicri:regionArea>
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<author><name sortKey="Mo, Ruo" sort="Mo, Ruo" uniqKey="Mo R" first="Ruo" last="Mo">Ruo Mo</name>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000</wicri:regionArea>
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<author><name sortKey="Jin, Hongli" sort="Jin, Hongli" uniqKey="Jin H" first="Hongli" last="Jin">Hongli Jin</name>
<affiliation wicri:level="1"><nlm:affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000</wicri:regionArea>
<placeName><settlement type="city">Changchun</settlement>
<region type="province">Jilin</region>
<region type="groupement">Dongbei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wang, Hualei" sort="Wang, Hualei" uniqKey="Wang H" first="Hualei" last="Wang">Hualei Wang</name>
<affiliation wicri:level="1"><nlm:affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000</wicri:regionArea>
<placeName><settlement type="city">Changchun</settlement>
<region type="province">Jilin</region>
<region type="groupement">Dongbei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Feng, Na" sort="Feng, Na" uniqKey="Feng N" first="Na" last="Feng">Na Feng</name>
<affiliation wicri:level="1"><nlm:affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000</wicri:regionArea>
<placeName><settlement type="city">Changchun</settlement>
<region type="province">Jilin</region>
<region type="groupement">Dongbei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wang, Jianzhong" sort="Wang, Jianzhong" uniqKey="Wang J" first="Jianzhong" last="Wang">Jianzhong Wang</name>
<affiliation wicri:level="1"><nlm:affiliation>Animal Science and Technology College, Jilin Agricultural University, Changchun 130118, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Animal Science and Technology College, Jilin Agricultural University, Changchun 130118</wicri:regionArea>
<placeName><settlement type="city">Changchun</settlement>
<region type="province">Jilin</region>
<region type="groupement">Dongbei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bi, Yuhai" sort="Bi, Yuhai" uniqKey="Bi Y" first="Yuhai" last="Bi">Yuhai Bi</name>
<affiliation wicri:level="1"><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wang, Tiecheng" sort="Wang, Tiecheng" uniqKey="Wang T" first="Tiecheng" last="Wang">Tiecheng Wang</name>
<affiliation wicri:level="1"><nlm:affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000</wicri:regionArea>
<placeName><settlement type="city">Changchun</settlement>
<region type="province">Jilin</region>
<region type="groupement">Dongbei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Sun, Weiyang" sort="Sun, Weiyang" uniqKey="Sun W" first="Weiyang" last="Sun">Weiyang Sun</name>
<affiliation wicri:level="1"><nlm:affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000</wicri:regionArea>
<placeName><settlement type="city">Changchun</settlement>
<region type="province">Jilin</region>
<region type="groupement">Dongbei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gao, Yuwei" sort="Gao, Yuwei" uniqKey="Gao Y" first="Yuwei" last="Gao">Yuwei Gao</name>
<affiliation wicri:level="1"><nlm:affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000</wicri:regionArea>
<placeName><settlement type="city">Changchun</settlement>
<region type="province">Jilin</region>
<region type="groupement">Dongbei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zhao, Yongkun" sort="Zhao, Yongkun" uniqKey="Zhao Y" first="Yongkun" last="Zhao">Yongkun Zhao</name>
<affiliation wicri:level="1"><nlm:affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China. zhaoyongkun1976@126.com.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000</wicri:regionArea>
<placeName><settlement type="city">Changchun</settlement>
<region type="province">Jilin</region>
<region type="groupement">Dongbei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yang, Songtao" sort="Yang, Songtao" uniqKey="Yang S" first="Songtao" last="Yang">Songtao Yang</name>
<affiliation wicri:level="1"><nlm:affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China. yst62041@163.com.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000</wicri:regionArea>
<placeName><settlement type="city">Changchun</settlement>
<region type="province">Jilin</region>
<region type="groupement">Dongbei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Xia, Xianzhu" sort="Xia, Xianzhu" uniqKey="Xia X" first="Xianzhu" last="Xia">Xianzhu Xia</name>
<affiliation wicri:level="1"><nlm:affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China. xiaxzh@cae.cn.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000</wicri:regionArea>
<placeName><settlement type="city">Changchun</settlement>
<region type="province">Jilin</region>
<region type="groupement">Dongbei</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Viruses</title>
<idno type="eISSN">1999-4915</idno>
<imprint><date when="2019" type="published">2019</date>
</imprint>
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<front><div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV), a new coronavirus that has been causing severe and fatal acute respiratory illnesses in humans since its outbreak in 2012, has raised public fear worldwide. The development of prophylactics and therapeutics is urgently needed to prevent and control MERS-CoV infections. In this study, a bacterium (<i>Lactococcus lactis</i>
)-like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). The designs included different numbers of lysin motif (LysM) repeats in the PAs linked by linkers (RBD-linker-PA2 (RLP<sub>2</sub>
), RBD-linker-PA3 (RLP<sub>3</sub>
) and RBD-PA3 (RP<sub>3</sub>
)), and three LysM repeats and a linker in the fusion proteins increased the binding activity to the RBD. The specific immune responses were tested by intranasally immunizing mice with RLP<sub>3</sub>
-GEM with or without the adjuvant GEL01. The results showed that GEL01-adjuvanted RLP<sub>3</sub>
-GEM increased the systemic humoral, cellular and local mucosal immune responses in the mouse model, especially in the intestinal tract. The above results indicate that the MERS-CoV BLP product has the potential to be developed into a promising mucosal candidate vaccine to protect against MERS-CoV infections.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">31470645</PMID>
<DateRevised><Year>2019</Year>
<Month>10</Month>
<Day>23</Day>
</DateRevised>
<Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1999-4915</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>11</Volume>
<Issue>9</Issue>
<PubDate><Year>2019</Year>
<Month>Aug</Month>
<Day>29</Day>
</PubDate>
</JournalIssue>
<Title>Viruses</Title>
<ISOAbbreviation>Viruses</ISOAbbreviation>
</Journal>
<ArticleTitle>A Novel Bacterium-Like Particle Vaccine Displaying the MERS-CoV Receptor-Binding Domain Induces Specific Mucosal and Systemic Immune Responses in Mice.</ArticleTitle>
<ELocationID EIdType="pii" ValidYN="Y">E799</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.3390/v11090799</ELocationID>
<Abstract><AbstractText>Middle East respiratory syndrome coronavirus (MERS-CoV), a new coronavirus that has been causing severe and fatal acute respiratory illnesses in humans since its outbreak in 2012, has raised public fear worldwide. The development of prophylactics and therapeutics is urgently needed to prevent and control MERS-CoV infections. In this study, a bacterium (<i>Lactococcus lactis</i>
)-like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). The designs included different numbers of lysin motif (LysM) repeats in the PAs linked by linkers (RBD-linker-PA2 (RLP<sub>2</sub>
), RBD-linker-PA3 (RLP<sub>3</sub>
) and RBD-PA3 (RP<sub>3</sub>
)), and three LysM repeats and a linker in the fusion proteins increased the binding activity to the RBD. The specific immune responses were tested by intranasally immunizing mice with RLP<sub>3</sub>
-GEM with or without the adjuvant GEL01. The results showed that GEL01-adjuvanted RLP<sub>3</sub>
-GEM increased the systemic humoral, cellular and local mucosal immune responses in the mouse model, especially in the intestinal tract. The above results indicate that the MERS-CoV BLP product has the potential to be developed into a promising mucosal candidate vaccine to protect against MERS-CoV infections.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Li</LastName>
<ForeName>Entao</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chi</LastName>
<ForeName>Hang</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China. ch_amms@163.com.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China. ch_amms@163.com.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Huang</LastName>
<ForeName>Pei</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Animal Science and Technology College, Jilin Agricultural University, Changchun 130118, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yan</LastName>
<ForeName>Feihu</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhang</LastName>
<ForeName>Ying</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Liu</LastName>
<ForeName>Chuanyu</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Animal Science and Technology College, Jilin Agricultural University, Changchun 130118, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wang</LastName>
<ForeName>Zhenshan</ForeName>
<Initials>Z</Initials>
<AffiliationInfo><Affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Animal Science and Technology College, Jilin Agricultural University, Changchun 130118, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Li</LastName>
<ForeName>Guohua</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>College of Animal Science and Technology, Shihezi University, Shihezi 832003, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhang</LastName>
<ForeName>Shengnan</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mo</LastName>
<ForeName>Ruo</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Animal Science and Technology College, Jilin Agricultural University, Changchun 130118, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Jin</LastName>
<ForeName>Hongli</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>College of Veterinary Medicine, Jilin University, Changchun 130062, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wang</LastName>
<ForeName>Hualei</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>College of Veterinary Medicine, Jilin University, Changchun 130062, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Feng</LastName>
<ForeName>Na</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wang</LastName>
<ForeName>Jianzhong</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Animal Science and Technology College, Jilin Agricultural University, Changchun 130118, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bi</LastName>
<ForeName>Yuhai</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wang</LastName>
<ForeName>Tiecheng</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sun</LastName>
<ForeName>Weiyang</ForeName>
<Initials>W</Initials>
<AffiliationInfo><Affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gao</LastName>
<ForeName>Yuwei</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhao</LastName>
<ForeName>Yongkun</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China. zhaoyongkun1976@126.com.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China. zhaoyongkun1976@126.com.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yang</LastName>
<ForeName>Songtao</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China. yst62041@163.com.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China. yst62041@163.com.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Xia</LastName>
<ForeName>Xianzhu</ForeName>
<Initials>X</Initials>
<AffiliationInfo><Affiliation>Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China. xiaxzh@cae.cn.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China. xiaxzh@cae.cn.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>2017YFD0501804</GrantID>
<Agency>National Project for Prevention and Control of Transboundary Animal Diseases</Agency>
<Country></Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2019</Year>
<Month>08</Month>
<Day>29</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>Switzerland</Country>
<MedlineTA>Viruses</MedlineTA>
<NlmUniqueID>101509722</NlmUniqueID>
<ISSNLinking>1999-4915</ISSNLinking>
</MedlineJournalInfo>
<CitationSubset>IM</CitationSubset>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">MERS-CoV</Keyword>
<Keyword MajorTopicYN="N">bacterium-like particles</Keyword>
<Keyword MajorTopicYN="N">intranasal administration</Keyword>
<Keyword MajorTopicYN="N">mucosal immune</Keyword>
<Keyword MajorTopicYN="N">subunit vaccine</Keyword>
</KeywordList>
<CoiStatement>The authors declare no conflicts of interest.</CoiStatement>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year>
<Month>07</Month>
<Day>19</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2019</Year>
<Month>08</Month>
<Day>26</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2019</Year>
<Month>08</Month>
<Day>27</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2019</Year>
<Month>9</Month>
<Day>1</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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<Month>9</Month>
<Day>1</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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<Minute>0</Minute>
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<affiliations><list><country><li>République populaire de Chine</li>
</country>
<region><li>Dongbei</li>
<li>Guangdong</li>
<li>Jilin</li>
</region>
<settlement><li>Changchun</li>
<li>Jiangmen</li>
<li>Pékin</li>
</settlement>
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<tree><country name="République populaire de Chine"><region name="Guangdong"><name sortKey="Li, Entao" sort="Li, Entao" uniqKey="Li E" first="Entao" last="Li">Entao Li</name>
</region>
<name sortKey="Bi, Yuhai" sort="Bi, Yuhai" uniqKey="Bi Y" first="Yuhai" last="Bi">Yuhai Bi</name>
<name sortKey="Chi, Hang" sort="Chi, Hang" uniqKey="Chi H" first="Hang" last="Chi">Hang Chi</name>
<name sortKey="Feng, Na" sort="Feng, Na" uniqKey="Feng N" first="Na" last="Feng">Na Feng</name>
<name sortKey="Gao, Yuwei" sort="Gao, Yuwei" uniqKey="Gao Y" first="Yuwei" last="Gao">Yuwei Gao</name>
<name sortKey="Huang, Pei" sort="Huang, Pei" uniqKey="Huang P" first="Pei" last="Huang">Pei Huang</name>
<name sortKey="Jin, Hongli" sort="Jin, Hongli" uniqKey="Jin H" first="Hongli" last="Jin">Hongli Jin</name>
<name sortKey="Li, Guohua" sort="Li, Guohua" uniqKey="Li G" first="Guohua" last="Li">Guohua Li</name>
<name sortKey="Liu, Chuanyu" sort="Liu, Chuanyu" uniqKey="Liu C" first="Chuanyu" last="Liu">Chuanyu Liu</name>
<name sortKey="Mo, Ruo" sort="Mo, Ruo" uniqKey="Mo R" first="Ruo" last="Mo">Ruo Mo</name>
<name sortKey="Sun, Weiyang" sort="Sun, Weiyang" uniqKey="Sun W" first="Weiyang" last="Sun">Weiyang Sun</name>
<name sortKey="Wang, Hualei" sort="Wang, Hualei" uniqKey="Wang H" first="Hualei" last="Wang">Hualei Wang</name>
<name sortKey="Wang, Jianzhong" sort="Wang, Jianzhong" uniqKey="Wang J" first="Jianzhong" last="Wang">Jianzhong Wang</name>
<name sortKey="Wang, Tiecheng" sort="Wang, Tiecheng" uniqKey="Wang T" first="Tiecheng" last="Wang">Tiecheng Wang</name>
<name sortKey="Wang, Zhenshan" sort="Wang, Zhenshan" uniqKey="Wang Z" first="Zhenshan" last="Wang">Zhenshan Wang</name>
<name sortKey="Xia, Xianzhu" sort="Xia, Xianzhu" uniqKey="Xia X" first="Xianzhu" last="Xia">Xianzhu Xia</name>
<name sortKey="Yan, Feihu" sort="Yan, Feihu" uniqKey="Yan F" first="Feihu" last="Yan">Feihu Yan</name>
<name sortKey="Yang, Songtao" sort="Yang, Songtao" uniqKey="Yang S" first="Songtao" last="Yang">Songtao Yang</name>
<name sortKey="Zhang, Shengnan" sort="Zhang, Shengnan" uniqKey="Zhang S" first="Shengnan" last="Zhang">Shengnan Zhang</name>
<name sortKey="Zhang, Ying" sort="Zhang, Ying" uniqKey="Zhang Y" first="Ying" last="Zhang">Ying Zhang</name>
<name sortKey="Zhao, Yongkun" sort="Zhao, Yongkun" uniqKey="Zhao Y" first="Yongkun" last="Zhao">Yongkun Zhao</name>
</country>
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