Receptor-binding domain of SARS-CoV spike protein induces long-term protective immunity in an animal model
Identifieur interne : 003D52 ( Main/Exploration ); précédent : 003D51; suivant : 003D53Receptor-binding domain of SARS-CoV spike protein induces long-term protective immunity in an animal model
Auteurs : Lanying Du [République populaire de Chine] ; Guangyu Zhao [République populaire de Chine] ; Yuxian He [République populaire de Chine, États-Unis] ; Yan Guo [République populaire de Chine] ; Bo-Jian Zheng [République populaire de Chine] ; Shibo Jiang [États-Unis] ; Yusen Zhou [République populaire de Chine]Source :
- Vaccine [ 0264-410X ] ; 2006.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (biosynthèse), Anticorps antiviraux (immunologie), Cellules Vero, Femelle, Fragments peptidiques (immunologie), Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (immunologie), Poumon (anatomopathologie), Production d'anticorps (immunologie), Protéines de l'enveloppe virale (immunologie), Réplication virale, Souris, Souris de lignée BALB C, Spécificité des anticorps, Structure tertiaire des protéines, Syndrome respiratoire aigu sévère (), Syndrome respiratoire aigu sévère (immunologie), Vaccins antiviraux (immunologie), Vaccins antiviraux (pharmacologie), Vaccins sous-unitaires (immunologie), Vaccins sous-unitaires (pharmacologie), Virus du SRAS (), Virus du SRAS (immunologie), Virus du SRAS (physiologie).
- MESH :
- anatomopathologie : Poumon.
- biosynthèse : Anticorps antiviraux.
- immunologie : Anticorps antiviraux, Fragments peptidiques, Glycoprotéines membranaires, Production d'anticorps, Protéines de l'enveloppe virale, Syndrome respiratoire aigu sévère, Vaccins antiviraux, Vaccins sous-unitaires, Virus du SRAS.
- pharmacologie : Vaccins antiviraux, Vaccins sous-unitaires.
- physiologie : Virus du SRAS.
- Animaux, Cellules Vero, Femelle, Glycoprotéine de spicule des coronavirus, Réplication virale, Souris, Souris de lignée BALB C, Spécificité des anticorps, Structure tertiaire des protéines, Syndrome respiratoire aigu sévère, Virus du SRAS.
English descriptors
- KwdEn :
- Animals, Antibodies, Viral (biosynthesis), Antibodies, Viral (immunology), Antibody Formation (immunology), Antibody Specificity, Chlorocebus aethiops, Female, Lung (pathology), Membrane Glycoproteins (immunology), Mice, Mice, Inbred BALB C, Peptide Fragments (immunology), Protein Structure, Tertiary, SARS Virus (drug effects), SARS Virus (immunology), SARS Virus (physiology), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (prevention & control), Spike Glycoprotein, Coronavirus, Vaccines, Subunit (immunology), Vaccines, Subunit (pharmacology), Vero Cells, Viral Envelope Proteins (immunology), Viral Vaccines (immunology), Viral Vaccines (pharmacology), Virus Replication.
- MESH :
- chemical , biosynthesis : Antibodies, Viral.
- chemical , immunology : Antibodies, Viral, Membrane Glycoproteins, Peptide Fragments, Vaccines, Subunit, Viral Envelope Proteins, Viral Vaccines.
- drug effects : SARS Virus.
- immunology : Antibody Formation, SARS Virus, Severe Acute Respiratory Syndrome.
- pathology : Lung.
- chemical , pharmacology : Vaccines, Subunit, Viral Vaccines.
- physiology : SARS Virus.
- prevention & control : Severe Acute Respiratory Syndrome.
- Animals, Antibody Specificity, Chlorocebus aethiops, Female, Mice, Mice, Inbred BALB C, Protein Structure, Tertiary, Spike Glycoprotein, Coronavirus, Vero Cells, Virus Replication.
Abstract
Development of effective vaccines against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is still a priority in prevention of re-emergence of SARS. Our previous studies have shown that the receptor-binding domain (RBD) of SARS-CoV spike (S) protein elicits highly potent neutralizing antibody responses in the immunized animals. But it is unknown whether RBD can also induce protective immunity in an animal model, a key aspect for vaccine development. In this study, BALB/c mice were vaccinated intramuscularly (i.m.) with 10 μg of RBD-Fc (RBD fused with human IgG1 Fc) and boosted twice at 3-week intervals and one more time at 12th month. Humoral immune responses of vaccinated mice were investigated for up to 12 months at a 1-month interval and the neutralizing titers of produced antibodies were reported at months 0, 3, 6 and 12 post-vaccination. Mice were challenged with the homologous strain of SARS-CoV 5 days after the last boost, and sacrificed 5 days after the challenge. Mouse lung tissues were collected for detection of viral load, virus replication and histopathological effects. Our results showed that RBD-Fc vaccination induced high titer of S-specific antibodies with long-term and potent SARS-CoV neutralizing activity. Four of five vaccinated mice were protected from subsequent SARS-CoV challenge because no significant virus replication, and no obvious histopathological changes were found in the lung tissues of the vaccinated mice challenged with SARS-CoV. Only one vaccinated mouse had mild alveolar damage in the lung tissues. In contrast, high copies of SARS-CoV RNA and virus replication were detected, and pathological changes were observed in the lung tissues of the control mice. In conclusion, our findings suggest that RBD, which can induce protective antibodies to SARS-CoV, may be further developed as a safe and effective SARS subunit vaccine.
Url:
DOI: 10.1016/j.vaccine.2006.10.031
PubMed: 17092615
PubMed Central: 7115660
Affiliations:
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Le document en format XML
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Kimball Research Institute, The New York Blood Center, New York, NY 10021, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, The New York Blood Center, New York, NY 10021</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Guo, Yan" sort="Guo, Yan" uniqKey="Guo Y" first="Yan" last="Guo">Yan Guo</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology & Epidemiology, Beijing 100071, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology & Epidemiology, Beijing 100071</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong SAR, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><affiliation wicri:level="2"><nlm:aff id="aff3">Lindsley F. Kimball Research Institute, The New York Blood Center, New York, NY 10021, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, The New York Blood Center, New York, NY 10021</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology & Epidemiology, Beijing 100071, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology & Epidemiology, Beijing 100071</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author></analytic><series><title level="j">Vaccine</title><idno type="ISSN">0264-410X</idno><idno type="eISSN">1873-2518</idno><imprint><date 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Envelope Proteins (immunology)</term><term>Viral Vaccines (immunology)</term><term>Viral Vaccines (pharmacology)</term><term>Virus Replication</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anticorps antiviraux (biosynthèse)</term><term>Anticorps antiviraux (immunologie)</term><term>Cellules Vero</term><term>Femelle</term><term>Fragments peptidiques (immunologie)</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires (immunologie)</term><term>Poumon (anatomopathologie)</term><term>Production d'anticorps (immunologie)</term><term>Protéines de l'enveloppe virale (immunologie)</term><term>Réplication virale</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Spécificité des anticorps</term><term>Structure tertiaire des protéines</term><term>Syndrome respiratoire aigu sévère ()</term><term>Syndrome respiratoire aigu sévère (immunologie)</term><term>Vaccins antiviraux (immunologie)</term><term>Vaccins antiviraux (pharmacologie)</term><term>Vaccins sous-unitaires (immunologie)</term><term>Vaccins sous-unitaires (pharmacologie)</term><term>Virus du SRAS ()</term><term>Virus du SRAS (immunologie)</term><term>Virus du SRAS (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Viral</term><term>Membrane Glycoproteins</term><term>Peptide Fragments</term><term>Vaccines, Subunit</term><term>Viral Envelope Proteins</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Anticorps antiviraux</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="immunologie" 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SRAS</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Development of effective vaccines against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is still a priority in prevention of re-emergence of SARS. Our previous studies have shown that the receptor-binding domain (RBD) of SARS-CoV spike (S) protein elicits highly potent neutralizing antibody responses in the immunized animals. But it is unknown whether RBD can also induce protective immunity in an animal model, a key aspect for vaccine development. In this study, BALB/c mice were vaccinated intramuscularly (i.m.) with 10 μg of RBD-Fc (RBD fused with human IgG1 Fc) and boosted twice at 3-week intervals and one more time at 12th month. Humoral immune responses of vaccinated mice were investigated for up to 12 months at a 1-month interval and the neutralizing titers of produced antibodies were reported at months 0, 3, 6 and 12 post-vaccination. Mice were challenged with the homologous strain of SARS-CoV 5 days after the last boost, and sacrificed 5 days after the challenge. Mouse lung tissues were collected for detection of viral load, virus replication and histopathological effects. Our results showed that RBD-Fc vaccination induced high titer of S-specific antibodies with long-term and potent SARS-CoV neutralizing activity. Four of five vaccinated mice were protected from subsequent SARS-CoV challenge because no significant virus replication, and no obvious histopathological changes were found in the lung tissues of the vaccinated mice challenged with SARS-CoV. Only one vaccinated mouse had mild alveolar damage in the lung tissues. In contrast, high copies of SARS-CoV RNA and virus replication were detected, and pathological changes were observed in the lung tissues of the control mice. In conclusion, our findings suggest that RBD, which can induce protective antibodies to SARS-CoV, may be further developed as a safe and effective SARS subunit vaccine.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Chinese Sars Molecular Epidemiology Consortium" uniqKey="Chinese Sars Molecular Epidemiology Consortium">Chinese SARS Molecular Epidemiology Consortium</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y. Guan</name></author><author><name sortKey="Zheng, B J" uniqKey="Zheng B">B.J. Zheng</name></author><author><name sortKey="He, Y Q" uniqKey="He Y">Y.Q. He</name></author><author><name sortKey="Liu, X L" uniqKey="Liu X">X.L. Liu</name></author><author><name sortKey="Zhuang, Z X" uniqKey="Zhuang Z">Z.X. Zhuang</name></author><author><name sortKey="Cheung, C L" uniqKey="Cheung C">C.L. 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Liu</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>État de New York</li></region><settlement><li>Pékin</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name></noRegion><name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name><name sortKey="Guo, Yan" sort="Guo, Yan" uniqKey="Guo Y" first="Yan" last="Guo">Yan Guo</name><name sortKey="He, Yuxian" sort="He, Yuxian" uniqKey="He Y" first="Yuxian" last="He">Yuxian He</name><name sortKey="Zhao, Guangyu" sort="Zhao, Guangyu" uniqKey="Zhao G" first="Guangyu" last="Zhao">Guangyu Zhao</name><name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name><name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name></country><country name="États-Unis"><region name="État de New York"><name sortKey="He, Yuxian" sort="He, Yuxian" uniqKey="He Y" first="Yuxian" last="He">Yuxian He</name></region><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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