Recombinant Receptor Binding Domain Protein Induces Partial Protective Immunity in Rhesus Macaques Against Middle East Respiratory Syndrome Coronavirus Challenge☆
Identifieur interne : 001596 ( Main/Exploration ); précédent : 001595; suivant : 001597Recombinant Receptor Binding Domain Protein Induces Partial Protective Immunity in Rhesus Macaques Against Middle East Respiratory Syndrome Coronavirus Challenge☆
Auteurs : Jiaming Lan [République populaire de Chine] ; Yanfeng Yao [République populaire de Chine] ; Yao Deng [République populaire de Chine] ; Hong Chen [République populaire de Chine] ; Guangwen Lu [République populaire de Chine] ; Wen Wang [République populaire de Chine] ; Linlin Bao [République populaire de Chine] ; Wei Deng [République populaire de Chine] ; Qiang Wei [République populaire de Chine] ; George F. Gao [République populaire de Chine] ; Chuan Qin [République populaire de Chine] ; Wenjie Tan [République populaire de Chine]Source :
- EBioMedicine [ 2352-3964 ] ; 2015.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (immunologie), Anticorps neutralisants (immunologie), Charge virale, Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Facteurs temps, Femelle, Immunisation, Immunité cellulaire (immunologie), Immunoglobuline G (immunologie), Infections à coronavirus (), Infections à coronavirus (anatomopathologie), Infections à coronavirus (immunologie), Infections à coronavirus (virologie), Macaca mulatta, Modèles animaux de maladie humaine, Mâle, Protéines recombinantes (administration et posologie), Protéines recombinantes (immunologie), Vaccins antiviraux (administration et posologie), Vaccins antiviraux (immunologie), Vaccins sous-unitaires (administration et posologie), Vaccins sous-unitaires (immunologie).
- MESH :
- administration et posologie : Protéines recombinantes, Vaccins antiviraux, Vaccins sous-unitaires.
- anatomopathologie : Infections à coronavirus.
- immunologie : Anticorps antiviraux, Anticorps neutralisants, Coronavirus du syndrome respiratoire du Moyen-Orient, Immunité cellulaire, Immunoglobuline G, Infections à coronavirus, Protéines recombinantes, Vaccins antiviraux, Vaccins sous-unitaires.
- virologie : Infections à coronavirus.
- Animaux, Charge virale, Facteurs temps, Femelle, Immunisation, Infections à coronavirus, Macaca mulatta, Modèles animaux de maladie humaine, Mâle.
English descriptors
- KwdEn :
- Animals, Antibodies, Neutralizing (immunology), Antibodies, Viral (immunology), Coronavirus Infections (immunology), Coronavirus Infections (pathology), Coronavirus Infections (prevention & control), Coronavirus Infections (virology), Disease Models, Animal, Female, Immunity, Cellular (immunology), Immunization, Immunoglobulin G (immunology), Macaca mulatta, Male, Middle East Respiratory Syndrome Coronavirus (immunology), Recombinant Proteins (administration & dosage), Recombinant Proteins (immunology), Time Factors, Vaccines, Subunit (administration & dosage), Vaccines, Subunit (immunology), Viral Load, Viral Vaccines (administration & dosage), Viral Vaccines (immunology).
- MESH :
- chemical , administration & dosage : Recombinant Proteins, Vaccines, Subunit, Viral Vaccines.
- chemical , immunology : Antibodies, Neutralizing, Antibodies, Viral, Immunoglobulin G, Recombinant Proteins, Vaccines, Subunit, Viral Vaccines.
- immunology : Coronavirus Infections, Immunity, Cellular, Middle East Respiratory Syndrome Coronavirus.
- pathology : Coronavirus Infections.
- prevention & control : Coronavirus Infections.
- virology : Coronavirus Infections.
- Animals, Disease Models, Animal, Female, Immunization, Macaca mulatta, Male, Time Factors, Viral Load.
Abstract
Development an effective vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV) is urgent and limited information is available on vaccination in nonhuman primate (NHP) model. We herein report of evaluating a recombinant receptor-binding domain (rRBD) protein vaccine in a rhesus macaque model.
Nine monkeys were randomly assigned to high-dose, low-dose and mock groups,which were immunized with different doses of rRBD plus alum adjuvant or adjuvant alone at different time points (0, 8, 25 weeks). Immunological analysis was conducted after each immunisation. Monkeys were challenged with MERS-CoV at 14 days after the final immunisation followed by observation for clinical signs and chest X-rays. Nasal, oropharyngeal and rectal swabs were also collected for analyses. Monkeys were euthanized 3 days after challenge and multiple specimens from tissues were collected for pathological, virological and immunological tests.
Robust and sustained immunological responses (including neutralisation antibody) were elicited by the rRBD vaccination. Besides, rRBD vaccination alleviated pneumonia with evidence of reduced tissue impairment and clinical manifestation in monkeys. Furthermore, the rRBD vaccine decreased viral load of lung, trachea and oropharyngeal swabs of monkeys. These data in NHP paves a way for further development of an effective human vaccine against MERS-CoV infection.
Url:
DOI: 10.1016/j.ebiom.2015.08.031
PubMed: 26629538
PubMed Central: 4634622
Affiliations:
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Le document en format XML
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sort="Lan, Jiaming" uniqKey="Lan J" first="Jiaming" last="Lan">Jiaming Lan</name><affiliation wicri:level="1"><nlm:aff id="af0005">Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="af0020">Department of Pathogenic Biology, Hebei Medical University, Shijiazhuang 050017, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pathogenic Biology, Hebei Medical University, Shijiazhuang 050017</wicri:regionArea><wicri:noRegion>Shijiazhuang 050017</wicri:noRegion></affiliation></author><author><name sortKey="Yao, Yanfeng" sort="Yao, Yanfeng" uniqKey="Yao Y" first="Yanfeng" last="Yao">Yanfeng Yao</name><affiliation wicri:level="3"><nlm:aff id="af0010">Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Deng, Yao" sort="Deng, Yao" uniqKey="Deng Y" first="Yao" last="Deng">Yao Deng</name><affiliation wicri:level="1"><nlm:aff id="af0005">Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Chen, Hong" sort="Chen, Hong" uniqKey="Chen H" first="Hong" last="Chen">Hong Chen</name><affiliation wicri:level="1"><nlm:aff id="af0005">Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Lu, Guangwen" sort="Lu, Guangwen" uniqKey="Lu G" first="Guangwen" last="Lu">Guangwen Lu</name><affiliation wicri:level="1"><nlm:aff id="af0015">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China</nlm:aff><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, Wen" sort="Wang, Wen" uniqKey="Wang W" first="Wen" last="Wang">Wen Wang</name><affiliation wicri:level="1"><nlm:aff id="af0005">Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Bao, Linlin" sort="Bao, Linlin" uniqKey="Bao L" first="Linlin" last="Bao">Linlin Bao</name><affiliation wicri:level="3"><nlm:aff id="af0010">Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Deng, Wei" sort="Deng, Wei" uniqKey="Deng W" first="Wei" last="Deng">Wei Deng</name><affiliation wicri:level="3"><nlm:aff id="af0010">Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Wei, Qiang" sort="Wei, Qiang" uniqKey="Wei Q" first="Qiang" last="Wei">Qiang Wei</name><affiliation wicri:level="3"><nlm:aff id="af0010">Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name><affiliation wicri:level="1"><nlm:aff id="af0015">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China</nlm:aff><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="Qin, Chuan" sort="Qin, Chuan" uniqKey="Qin C" first="Chuan" last="Qin">Chuan Qin</name><affiliation wicri:level="3"><nlm:aff id="af0010">Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name><affiliation wicri:level="1"><nlm:aff id="af0005">Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author></analytic><series><title level="j">EBioMedicine</title><idno type="eISSN">2352-3964</idno><imprint><date when="2015">2015</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>Coronavirus Infections (immunology)</term><term>Coronavirus Infections (pathology)</term><term>Coronavirus Infections (prevention & control)</term><term>Coronavirus Infections (virology)</term><term>Disease Models, Animal</term><term>Female</term><term>Immunity, Cellular (immunology)</term><term>Immunization</term><term>Immunoglobulin G (immunology)</term><term>Macaca mulatta</term><term>Male</term><term>Middle East Respiratory Syndrome Coronavirus (immunology)</term><term>Recombinant Proteins (administration & dosage)</term><term>Recombinant Proteins (immunology)</term><term>Time Factors</term><term>Vaccines, Subunit (administration & dosage)</term><term>Vaccines, Subunit (immunology)</term><term>Viral Load</term><term>Viral Vaccines (administration & dosage)</term><term>Viral Vaccines (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anticorps antiviraux (immunologie)</term><term>Anticorps neutralisants (immunologie)</term><term>Charge virale</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term><term>Facteurs temps</term><term>Femelle</term><term>Immunisation</term><term>Immunité cellulaire (immunologie)</term><term>Immunoglobuline G (immunologie)</term><term>Infections à coronavirus ()</term><term>Infections à coronavirus (anatomopathologie)</term><term>Infections à coronavirus (immunologie)</term><term>Infections à coronavirus (virologie)</term><term>Macaca mulatta</term><term>Modèles animaux de maladie humaine</term><term>Mâle</term><term>Protéines recombinantes (administration et posologie)</term><term>Protéines recombinantes (immunologie)</term><term>Vaccins antiviraux (administration et posologie)</term><term>Vaccins antiviraux (immunologie)</term><term>Vaccins sous-unitaires (administration et posologie)</term><term>Vaccins sous-unitaires (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Recombinant Proteins</term><term>Vaccines, Subunit</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>Immunoglobulin G</term><term>Recombinant Proteins</term><term>Vaccines, Subunit</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Protéines recombinantes</term><term>Vaccins antiviraux</term><term>Vaccins sous-unitaires</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Infections à coronavirus</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>Immunité cellulaire</term><term>Immunoglobuline G</term><term>Infections à coronavirus</term><term>Protéines recombinantes</term><term>Vaccins antiviraux</term><term>Vaccins sous-unitaires</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronavirus Infections</term><term>Immunity, Cellular</term><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="pathology" 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" qualifier="virologie" xml:lang="fr"><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Female</term><term>Immunization</term><term>Macaca mulatta</term><term>Male</term><term>Time Factors</term><term>Viral Load</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Charge virale</term><term>Facteurs temps</term><term>Femelle</term><term>Immunisation</term><term>Infections à coronavirus</term><term>Macaca mulatta</term><term>Modèles animaux de maladie humaine</term><term>Mâle</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Development an effective vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV) is urgent and limited information is available on vaccination in nonhuman primate (NHP) model. We herein report of evaluating a recombinant receptor-binding domain (rRBD) protein vaccine in a rhesus macaque model.</p></sec><sec><title>Methods</title><p>Nine monkeys were randomly assigned to high-dose, low-dose and mock groups,which were immunized with different doses of rRBD plus alum adjuvant or adjuvant alone at different time points (0, 8, 25 weeks). Immunological analysis was conducted after each immunisation. Monkeys were challenged with MERS-CoV at 14 days after the final immunisation followed by observation for clinical signs and chest X-rays. Nasal, oropharyngeal and rectal swabs were also collected for analyses. Monkeys were euthanized 3 days after challenge and multiple specimens from tissues were collected for pathological, virological and immunological tests.</p></sec><sec><title>Conclusion</title><p>Robust and sustained immunological responses (including neutralisation antibody) were elicited by the rRBD vaccination. Besides, rRBD vaccination alleviated pneumonia with evidence of reduced tissue impairment and clinical manifestation in monkeys. Furthermore, the rRBD vaccine decreased viral load of lung, trachea and oropharyngeal swabs of monkeys. These data in NHP paves a way for further development of an effective human vaccine against MERS-CoV infection.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Agrawal, A S" uniqKey="Agrawal A">A.S. Agrawal</name></author><author><name sortKey="Garron, T" uniqKey="Garron T">T. Garron</name></author><author><name sortKey="Tao, X" uniqKey="Tao X">X. Tao</name></author><author><name sortKey="Peng, B" uniqKey="Peng B">B. Peng</name></author><author><name sortKey="Wakamiya, M" uniqKey="Wakamiya M">M. Wakamiya</name></author><author><name sortKey="Chan, T" uniqKey="Chan T">T. Chan</name></author><author><name sortKey="Couch, R B" uniqKey="Couch R">R.B. 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Perlman</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country><settlement><li>Pékin</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Lan, Jiaming" sort="Lan, Jiaming" uniqKey="Lan J" first="Jiaming" last="Lan">Jiaming Lan</name></noRegion><name sortKey="Bao, Linlin" sort="Bao, Linlin" uniqKey="Bao L" first="Linlin" last="Bao">Linlin Bao</name><name sortKey="Chen, Hong" sort="Chen, Hong" uniqKey="Chen H" first="Hong" last="Chen">Hong Chen</name><name sortKey="Deng, Wei" sort="Deng, Wei" uniqKey="Deng W" first="Wei" last="Deng">Wei Deng</name><name sortKey="Deng, Yao" sort="Deng, Yao" uniqKey="Deng Y" first="Yao" last="Deng">Yao Deng</name><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name><name sortKey="Lan, Jiaming" sort="Lan, Jiaming" uniqKey="Lan J" first="Jiaming" last="Lan">Jiaming Lan</name><name sortKey="Lu, Guangwen" sort="Lu, Guangwen" uniqKey="Lu G" first="Guangwen" last="Lu">Guangwen Lu</name><name sortKey="Qin, Chuan" sort="Qin, Chuan" uniqKey="Qin C" first="Chuan" last="Qin">Chuan Qin</name><name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name><name sortKey="Wang, Wen" sort="Wang, Wen" uniqKey="Wang W" first="Wen" last="Wang">Wen Wang</name><name sortKey="Wei, Qiang" sort="Wei, Qiang" uniqKey="Wei Q" first="Qiang" last="Wei">Qiang Wei</name><name sortKey="Yao, Yanfeng" sort="Yao, Yanfeng" uniqKey="Yao Y" first="Yanfeng" last="Yao">Yanfeng Yao</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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