Development of a recombinant replication-deficient rabies virus-based bivalent-vaccine against MERS-CoV and rabies virus and its humoral immunogenicity in mice
Identifieur interne : 000619 ( Main/Exploration ); précédent : 000618; suivant : 000620Development of a recombinant replication-deficient rabies virus-based bivalent-vaccine against MERS-CoV and rabies virus and its humoral immunogenicity in mice
Auteurs : Hirofumi Kato [Japon] ; Mutsuyo Takayama-Ito [Japon] ; Itoe Iizuka-Shiota [Japon] ; Shuetsu Fukushi [Japon] ; Guillermo Posadas-Herrera [Japon] ; Madoka Horiya [Japon] ; Masaaki Satoh [Japon] ; Tomoki Yoshikawa [Japon] ; Souichi Yamada [Japon] ; Shizuko Harada [Japon] ; Hikaru Fujii [Japon] ; Miho Shibamura [Japon] ; Takuya Inagaki [Japon] ; Kinjiro Morimoto [Japon] ; Masayuki Saijo [Japon] ; Chang-Kweng Lim [Japon]Source :
- PLoS ONE [ 1932-6203 ] ; 2019.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (immunologie), Anticorps neutralisants (immunologie), Cellules HEK293, Cellules Vero, Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Femelle, Glycoprotéine de spicule des coronavirus (immunologie), Humains, Immunogénicité des vaccins, Infections à coronavirus (), Lignée cellulaire tumorale, Réplication virale, Souris, Souris de lignée BALB C, Souris de lignée ICR, Vaccins antiviraux (génétique), Vaccins antiviraux (immunologie), Vaccins synthétiques (génétique), Vaccins synthétiques (immunologie), Virus de la rage (génétique), Virus de la rage (physiologie).
- MESH :
- génétique : Vaccins antiviraux, Vaccins synthétiques, Virus de la rage.
- immunologie : Anticorps antiviraux, Anticorps neutralisants, Coronavirus du syndrome respiratoire du Moyen-Orient, Glycoprotéine de spicule des coronavirus, Vaccins antiviraux, Vaccins synthétiques.
- physiologie : Virus de la rage.
- Animaux, Cellules HEK293, Cellules Vero, Femelle, Humains, Immunogénicité des vaccins, Infections à coronavirus, Lignée cellulaire tumorale, Réplication virale, Souris, Souris de lignée BALB C, Souris de lignée ICR.
English descriptors
- KwdEn :
- Animals, Antibodies, Neutralizing (immunology), Antibodies, Viral (immunology), Cell Line, Tumor, Chlorocebus aethiops, Coronavirus Infections (prevention & control), Female, HEK293 Cells, Humans, Immunogenicity, Vaccine, Mice, Mice, Inbred BALB C, Mice, Inbred ICR, Middle East Respiratory Syndrome Coronavirus (immunology), Rabies virus (genetics), Rabies virus (physiology), Spike Glycoprotein, Coronavirus (immunology), Vaccines, Synthetic (genetics), Vaccines, Synthetic (immunology), Vero Cells, Viral Vaccines (genetics), Viral Vaccines (immunology), Virus Replication.
- MESH :
- chemical , genetics : Vaccines, Synthetic, Viral Vaccines.
- chemical , immunology : Antibodies, Neutralizing, Antibodies, Viral, Spike Glycoprotein, Coronavirus, Vaccines, Synthetic, Viral Vaccines.
- genetics : Rabies virus.
- immunology : Middle East Respiratory Syndrome Coronavirus.
- physiology : Rabies virus.
- prevention & control : Coronavirus Infections.
- Animals, Cell Line, Tumor, Chlorocebus aethiops, Female, HEK293 Cells, Humans, Immunogenicity, Vaccine, Mice, Mice, Inbred BALB C, Mice, Inbred ICR, Vero Cells, Virus Replication.
Abstract
Middle East respiratory syndrome-coronavirus (MERS-CoV) is an emerging virus that causes severe disease with fatal outcomes; however, there are currently no approved vaccines or specific treatments against MERS-CoV. Here, we developed a novel bivalent vaccine against MERS-CoV and rabies virus (RV) using the replication-incompetent P-gene-deficient RV (RVΔP), which has been previously established as a promising and safe viral vector. MERS-CoV spike glycoprotein comprises S1 and S2 subunits, with the S1 subunit being a primary target of neutralizing antibodies. Recombinant RVΔP, which expresses S1 fused with transmembrane and cytoplasmic domains together with 14 amino acids from the ectodomains of the RV-glycoprotein (RV-G), was developed using a reverse genetics method and named RVΔP-MERS/S1. Following generation of RVΔP-MERS/S1 and RVΔP, our analysis revealed that they shared similar growth properties, with the expression of S1 in RVΔP-MERS/S1-infected cells confirmed by immunofluorescence and western blot, and the immunogenicity and pathogenicity evaluated using mouse infection experiments. We observed no rabies-associated signs or symptoms in mice inoculated with RVΔP-MERS/S1. Moreover, virus-specific neutralizing antibodies against both MERS-CoV and RV were induced in mice inoculated intraperitoneally with RVΔP-MERS/S1. These findings indicate that RVΔP-MERS/S1 is a promising and safe bivalent-vaccine candidate against both MERS-CoV and RV.
Url:
DOI: 10.1371/journal.pone.0223684
PubMed: 31589656
PubMed Central: 6779238
Affiliations:
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Le document en format XML
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xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Yamada, Souichi" sort="Yamada, Souichi" uniqKey="Yamada S" first="Souichi" last="Yamada">Souichi Yamada</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Harada, Shizuko" sort="Harada, Shizuko" uniqKey="Harada S" first="Shizuko" last="Harada">Shizuko Harada</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Fujii, Hikaru" sort="Fujii, Hikaru" uniqKey="Fujii H" first="Hikaru" last="Fujii">Hikaru Fujii</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Shibamura, Miho" sort="Shibamura, Miho" uniqKey="Shibamura M" first="Miho" last="Shibamura">Miho Shibamura</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Inagaki, Takuya" sort="Inagaki, Takuya" uniqKey="Inagaki T" first="Takuya" last="Inagaki">Takuya Inagaki</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Department of Life Science and Medical Bioscience, Waseda University, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Life Science and Medical Bioscience, Waseda University, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Morimoto, Kinjiro" sort="Morimoto, Kinjiro" uniqKey="Morimoto K" first="Kinjiro" last="Morimoto">Kinjiro Morimoto</name><affiliation wicri:level="1"><nlm:aff 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Kweng" uniqKey="Lim C" first="Chang-Kweng" last="Lim">Chang-Kweng Lim</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31589656</idno><idno type="pmc">6779238</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779238</idno><idno type="RBID">PMC:6779238</idno><idno type="doi">10.1371/journal.pone.0223684</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">001053</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" 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Kantō</region></placeName></affiliation></author><author><name sortKey="Takayama Ito, Mutsuyo" sort="Takayama Ito, Mutsuyo" uniqKey="Takayama Ito M" first="Mutsuyo" last="Takayama-Ito">Mutsuyo Takayama-Ito</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Iizuka Shiota, Itoe" sort="Iizuka Shiota, Itoe" uniqKey="Iizuka Shiota I" first="Itoe" last="Iizuka-Shiota">Itoe Iizuka-Shiota</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Fukushi, Shuetsu" sort="Fukushi, Shuetsu" uniqKey="Fukushi S" first="Shuetsu" last="Fukushi">Shuetsu Fukushi</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Posadas Herrera, Guillermo" sort="Posadas Herrera, Guillermo" uniqKey="Posadas Herrera G" first="Guillermo" last="Posadas-Herrera">Guillermo Posadas-Herrera</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Horiya, Madoka" sort="Horiya, Madoka" uniqKey="Horiya M" first="Madoka" last="Horiya">Madoka Horiya</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Satoh, Masaaki" sort="Satoh, Masaaki" uniqKey="Satoh M" first="Masaaki" last="Satoh">Masaaki Satoh</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Yoshikawa, Tomoki" sort="Yoshikawa, Tomoki" uniqKey="Yoshikawa T" first="Tomoki" last="Yoshikawa">Tomoki Yoshikawa</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Yamada, Souichi" sort="Yamada, Souichi" uniqKey="Yamada S" first="Souichi" last="Yamada">Souichi Yamada</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Harada, Shizuko" sort="Harada, Shizuko" uniqKey="Harada S" first="Shizuko" last="Harada">Shizuko Harada</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Fujii, Hikaru" sort="Fujii, Hikaru" uniqKey="Fujii H" first="Hikaru" last="Fujii">Hikaru Fujii</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Shibamura, Miho" sort="Shibamura, Miho" uniqKey="Shibamura M" first="Miho" last="Shibamura">Miho Shibamura</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Inagaki, Takuya" sort="Inagaki, Takuya" uniqKey="Inagaki T" first="Takuya" last="Inagaki">Takuya Inagaki</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Department of Life Science and Medical Bioscience, Waseda University, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Life Science and Medical Bioscience, Waseda University, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Morimoto, Kinjiro" sort="Morimoto, Kinjiro" uniqKey="Morimoto K" first="Kinjiro" last="Morimoto">Kinjiro Morimoto</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Department of Pharmacy, Yasuda Women’s University, Hiroshima, Hiroshima, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pharmacy, Yasuda Women’s University, Hiroshima, Hiroshima</wicri:regionArea><wicri:noRegion>Hiroshima</wicri:noRegion></affiliation></author><author><name sortKey="Saijo, Masayuki" sort="Saijo, Masayuki" uniqKey="Saijo M" first="Masayuki" last="Saijo">Masayuki Saijo</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Lim, Chang Kweng" sort="Lim, Chang Kweng" uniqKey="Lim C" first="Chang-Kweng" last="Lim">Chang-Kweng Lim</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Neutralizing (immunology)</term><term>Antibodies, Viral (immunology)</term><term>Cell Line, Tumor</term><term>Chlorocebus aethiops</term><term>Coronavirus Infections (prevention & control)</term><term>Female</term><term>HEK293 Cells</term><term>Humans</term><term>Immunogenicity, Vaccine</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mice, Inbred ICR</term><term>Middle East Respiratory Syndrome Coronavirus (immunology)</term><term>Rabies virus (genetics)</term><term>Rabies virus (physiology)</term><term>Spike Glycoprotein, Coronavirus (immunology)</term><term>Vaccines, Synthetic (genetics)</term><term>Vaccines, Synthetic (immunology)</term><term>Vero Cells</term><term>Viral Vaccines (genetics)</term><term>Viral Vaccines (immunology)</term><term>Virus Replication</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anticorps antiviraux (immunologie)</term><term>Anticorps neutralisants (immunologie)</term><term>Cellules HEK293</term><term>Cellules Vero</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term><term>Femelle</term><term>Glycoprotéine de spicule des coronavirus (immunologie)</term><term>Humains</term><term>Immunogénicité des vaccins</term><term>Infections à coronavirus ()</term><term>Lignée cellulaire tumorale</term><term>Réplication virale</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Souris de lignée ICR</term><term>Vaccins antiviraux (génétique)</term><term>Vaccins antiviraux (immunologie)</term><term>Vaccins synthétiques (génétique)</term><term>Vaccins synthétiques (immunologie)</term><term>Virus de la rage (génétique)</term><term>Virus de la rage (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Vaccines, Synthetic</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</term><term>Spike Glycoprotein, Coronavirus</term><term>Vaccines, Synthetic</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Rabies virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Vaccins antiviraux</term><term>Vaccins synthétiques</term><term>Virus de la rage</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps neutralisants</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Glycoprotéine de spicule des coronavirus</term><term>Vaccins antiviraux</term><term>Vaccins synthétiques</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus de la rage</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Rabies virus</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Chlorocebus aethiops</term><term>Female</term><term>HEK293 Cells</term><term>Humans</term><term>Immunogenicity, Vaccine</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mice, Inbred ICR</term><term>Vero Cells</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules HEK293</term><term>Cellules Vero</term><term>Femelle</term><term>Humains</term><term>Immunogénicité des vaccins</term><term>Infections à coronavirus</term><term>Lignée cellulaire tumorale</term><term>Réplication virale</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Souris de lignée ICR</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Middle East respiratory syndrome-coronavirus (MERS-CoV) is an emerging virus that causes severe disease with fatal outcomes; however, there are currently no approved vaccines or specific treatments against MERS-CoV. Here, we developed a novel bivalent vaccine against MERS-CoV and rabies virus (RV) using the replication-incompetent P-gene-deficient RV (RVΔP), which has been previously established as a promising and safe viral vector. MERS-CoV spike glycoprotein comprises S1 and S2 subunits, with the S1 subunit being a primary target of neutralizing antibodies. Recombinant RVΔP, which expresses S1 fused with transmembrane and cytoplasmic domains together with 14 amino acids from the ectodomains of the RV-glycoprotein (RV-G), was developed using a reverse genetics method and named RVΔP-MERS/S1. Following generation of RVΔP-MERS/S1 and RVΔP, our analysis revealed that they shared similar growth properties, with the expression of S1 in RVΔP-MERS/S1-infected cells confirmed by immunofluorescence and western blot, and the immunogenicity and pathogenicity evaluated using mouse infection experiments. We observed no rabies-associated signs or symptoms in mice inoculated with RVΔP-MERS/S1. Moreover, virus-specific neutralizing antibodies against both MERS-CoV and RV were induced in mice inoculated intraperitoneally with RVΔP-MERS/S1. These findings indicate that RVΔP-MERS/S1 is a promising and safe bivalent-vaccine candidate against both MERS-CoV and RV.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zumla, A" uniqKey="Zumla A">A Zumla</name></author><author><name sortKey="Hui, Ds" uniqKey="Hui D">DS Hui</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S Perlman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, Jfw" uniqKey="Chan J">JFW Chan</name></author><author><name sortKey="Lau, Skp" uniqKey="Lau S">SKP Lau</name></author><author><name sortKey="To, Kkw" uniqKey="To K">KKW To</name></author><author><name sortKey="Cheng, Vcc" uniqKey="Cheng V">VCC Cheng</name></author><author><name sortKey="Woo, Pcy" uniqKey="Woo P">PCY Woo</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K-Y Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zaki, Am" 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N" uniqKey="Iwata Yoshikawa N">N Iwata-Yoshikawa</name></author><author><name sortKey="Uda, A" uniqKey="Uda A">A Uda</name></author><author><name sortKey="Suzuki, T" uniqKey="Suzuki T">T Suzuki</name></author><author><name sortKey="Tsunetsugu Yokota, Y" uniqKey="Tsunetsugu Yokota Y">Y Tsunetsugu-Yokota</name></author><author><name sortKey="Sato, Y" uniqKey="Sato Y">Y Sato</name></author><author><name sortKey="Morikawa, S" uniqKey="Morikawa S">S Morikawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reusken, Cbem" uniqKey="Reusken C">CBEM Reusken</name></author><author><name sortKey="Messadi, L" uniqKey="Messadi L">L Messadi</name></author><author><name sortKey="Feyisa, A" uniqKey="Feyisa A">A Feyisa</name></author><author><name sortKey="Ularamu, H" uniqKey="Ularamu H">H Ularamu</name></author><author><name sortKey="Godeke, G J" uniqKey="Godeke G">G-J Godeke</name></author><author><name sortKey="Danmarwa, A" uniqKey="Danmarwa A">A Danmarwa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reusken, Cb" uniqKey="Reusken C">CB Reusken</name></author><author><name sortKey="Haagmans, Bl" uniqKey="Haagmans B">BL Haagmans</name></author><author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Müller</name></author><author><name sortKey="Gutierrez, C" uniqKey="Gutierrez C">C Gutierrez</name></author><author><name sortKey="Godeke, G J" uniqKey="Godeke G">G-J Godeke</name></author><author><name sortKey="Meyer, B" uniqKey="Meyer B">B Meyer</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Japon</li></country><region><li>Région de Kantō</li></region><settlement><li>Tokyo</li></settlement></list><tree><country name="Japon"><region name="Région de Kantō"><name sortKey="Kato, Hirofumi" sort="Kato, Hirofumi" uniqKey="Kato H" first="Hirofumi" last="Kato">Hirofumi Kato</name></region><name sortKey="Fujii, Hikaru" sort="Fujii, Hikaru" uniqKey="Fujii H" first="Hikaru" last="Fujii">Hikaru Fujii</name><name sortKey="Fukushi, Shuetsu" sort="Fukushi, Shuetsu" uniqKey="Fukushi S" first="Shuetsu" last="Fukushi">Shuetsu Fukushi</name><name sortKey="Harada, Shizuko" sort="Harada, Shizuko" uniqKey="Harada S" first="Shizuko" last="Harada">Shizuko Harada</name><name sortKey="Horiya, Madoka" sort="Horiya, Madoka" uniqKey="Horiya M" first="Madoka" last="Horiya">Madoka Horiya</name><name sortKey="Iizuka Shiota, Itoe" sort="Iizuka Shiota, Itoe" uniqKey="Iizuka Shiota I" first="Itoe" last="Iizuka-Shiota">Itoe Iizuka-Shiota</name><name sortKey="Inagaki, Takuya" sort="Inagaki, Takuya" uniqKey="Inagaki T" first="Takuya" last="Inagaki">Takuya Inagaki</name><name sortKey="Inagaki, Takuya" sort="Inagaki, Takuya" uniqKey="Inagaki T" first="Takuya" last="Inagaki">Takuya Inagaki</name><name sortKey="Lim, Chang Kweng" sort="Lim, Chang Kweng" uniqKey="Lim C" first="Chang-Kweng" last="Lim">Chang-Kweng Lim</name><name sortKey="Morimoto, Kinjiro" sort="Morimoto, Kinjiro" uniqKey="Morimoto K" first="Kinjiro" last="Morimoto">Kinjiro Morimoto</name><name sortKey="Posadas Herrera, Guillermo" sort="Posadas Herrera, Guillermo" uniqKey="Posadas Herrera G" first="Guillermo" last="Posadas-Herrera">Guillermo Posadas-Herrera</name><name sortKey="Saijo, Masayuki" sort="Saijo, Masayuki" uniqKey="Saijo M" first="Masayuki" last="Saijo">Masayuki Saijo</name><name sortKey="Satoh, Masaaki" sort="Satoh, Masaaki" uniqKey="Satoh M" first="Masaaki" last="Satoh">Masaaki Satoh</name><name sortKey="Shibamura, Miho" sort="Shibamura, Miho" uniqKey="Shibamura M" first="Miho" last="Shibamura">Miho Shibamura</name><name sortKey="Takayama Ito, Mutsuyo" sort="Takayama Ito, Mutsuyo" uniqKey="Takayama Ito M" first="Mutsuyo" last="Takayama-Ito">Mutsuyo Takayama-Ito</name><name sortKey="Yamada, Souichi" sort="Yamada, Souichi" uniqKey="Yamada S" first="Souichi" last="Yamada">Souichi Yamada</name><name sortKey="Yoshikawa, Tomoki" sort="Yoshikawa, Tomoki" uniqKey="Yoshikawa T" first="Tomoki" last="Yoshikawa">Tomoki Yoshikawa</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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