Identification of a critical neutralization determinant of severe acute respiratory syndrome (SARS)-associated coronavirus: importance for designing SARS vaccines
Identifieur interne : 004807 ( Main/Exploration ); précédent : 004806; suivant : 004808Identification of a critical neutralization determinant of severe acute respiratory syndrome (SARS)-associated coronavirus: importance for designing SARS vaccines
Auteurs : Yuxian He [États-Unis] ; Qingyu Zhu [République populaire de Chine] ; Shuwen Liu [États-Unis] ; Yusen Zhou [République populaire de Chine] ; Baoan Yang [République populaire de Chine] ; Jiaming Li [République populaire de Chine] ; Shibo Jiang [États-Unis]Source :
- Virology [ 0042-6822 ] ; 2005.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (isolement et purification), Anticorps antiviraux (sang), Anticorps monoclonaux (isolement et purification), Antigènes viraux (), Antigènes viraux (génétique), Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (), Glycoprotéines membranaires (génétique), Glycoprotéines membranaires (immunologie), Humains, Lapins, Protéines de l'enveloppe virale (), Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (immunologie), Souris, Souris de lignée BALB C, Structure tertiaire des protéines, Syndrome respiratoire aigu sévère (), Syndrome respiratoire aigu sévère (immunologie), Syndrome respiratoire aigu sévère (virologie), Tests de neutralisation, Vaccins antiviraux (génétique), Vaccins antiviraux (immunologie), Virus du SRAS (génétique), Virus du SRAS (immunologie), Épitopes (), Épitopes (génétique).
- MESH :
- génétique : Antigènes viraux, Glycoprotéines membranaires, Protéines de l'enveloppe virale, Vaccins antiviraux, Virus du SRAS, Épitopes.
- immunologie : Glycoprotéines membranaires, Protéines de l'enveloppe virale, Syndrome respiratoire aigu sévère, Vaccins antiviraux, Virus du SRAS.
- isolement et purification : Anticorps antiviraux, Anticorps monoclonaux.
- sang : Anticorps antiviraux.
- virologie : Syndrome respiratoire aigu sévère.
- Animaux, Antigènes viraux, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Humains, Lapins, Protéines de l'enveloppe virale, Souris, Souris de lignée BALB C, Structure tertiaire des protéines, Syndrome respiratoire aigu sévère, Tests de neutralisation, Épitopes.
English descriptors
- KwdEn :
- Animals, Antibodies, Monoclonal (isolation & purification), Antibodies, Viral (blood), Antibodies, Viral (isolation & purification), Antigens, Viral (chemistry), Antigens, Viral (genetics), Epitopes (chemistry), Epitopes (genetics), Humans, Membrane Glycoproteins (chemistry), Membrane Glycoproteins (genetics), Membrane Glycoproteins (immunology), Mice, Mice, Inbred BALB C, Neutralization Tests, Protein Structure, Tertiary, Rabbits, SARS Virus (genetics), SARS Virus (immunology), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (prevention & control), Severe Acute Respiratory Syndrome (virology), Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (chemistry), Viral Envelope Proteins (genetics), Viral Envelope Proteins (immunology), Viral Vaccines (genetics), Viral Vaccines (immunology).
- MESH :
- chemical , blood : Antibodies, Viral.
- chemical , chemistry : Antigens, Viral, Epitopes, Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , genetics : Antigens, Viral, Epitopes, Membrane Glycoproteins, Viral Envelope Proteins, Viral Vaccines.
- chemical , immunology : Membrane Glycoproteins, Viral Envelope Proteins, Viral Vaccines.
- chemical , isolation & purification : Antibodies, Monoclonal, Antibodies, Viral.
- genetics : SARS Virus.
- immunology : SARS Virus, Severe Acute Respiratory Syndrome.
- prevention & control : Severe Acute Respiratory Syndrome.
- virology : Severe Acute Respiratory Syndrome.
- Animals, Humans, Mice, Mice, Inbred BALB C, Neutralization Tests, Protein Structure, Tertiary, Rabbits, Spike Glycoprotein, Coronavirus.
Abstract
The spike (S) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is not only responsible for receptor binding, but also a major antigenic determinant capable of inducing protective immunity. In this study, we demonstrated that the receptor-binding domain (RBD) of S protein is an important immunogenic site in patients with SARS and rabbits immunized with inactivated SARS-CoV. Serum samples from convalescent SARS patients and immunized rabbits had potent neutralizing activities against infection by pseudovirus expressing SARS-CoV S protein. Depletion of RBD-specific antibodies from patient or rabbit immune sera by immunoadsorption significantly reduced serum-mediated neutralizing activity, while affinity-purified anti-RBD antibodies had relatively higher potency neutralizing infectivity of SARS pseudovirus, indicating that the RBD of S protein is a critical neutralization determinant of SARS-CoV during viral infection and immunization. Two monoclonal antibodies (1A5 and 2C5) targeting at the RBD of S protein were isolated from mice immunized with inactivated SARS-CoV. Both 1A5 and 2C5 possessed potent neutralizing activities, although they directed against distinct conformation-dependant epitopes as shown by ELISA and binding competition assay. We further demonstrated that 2C5, but not 1A5, was able to block binding of the RBD to angiotensin-converting enzyme 2 (ACE2), the functional receptor on targeted cells. These data provide important information for understanding the antigenicity and immunogenicity of SARS-CoV and for designing SARS vaccines.
Url:
DOI: 10.1016/j.virol.2005.01.034
PubMed: 15749124
PubMed Central: 7111853
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en"><p>The spike (S) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is not only responsible for receptor binding, but also a major antigenic determinant capable of inducing protective immunity. In this study, we demonstrated that the receptor-binding domain (RBD) of S protein is an important immunogenic site in patients with SARS and rabbits immunized with inactivated SARS-CoV. Serum samples from convalescent SARS patients and immunized rabbits had potent neutralizing activities against infection by pseudovirus expressing SARS-CoV S protein. Depletion of RBD-specific antibodies from patient or rabbit immune sera by immunoadsorption significantly reduced serum-mediated neutralizing activity, while affinity-purified anti-RBD antibodies had relatively higher potency neutralizing infectivity of SARS pseudovirus, indicating that the RBD of S protein is a critical neutralization determinant of SARS-CoV during viral infection and immunization. Two monoclonal antibodies (1A5 and 2C5) targeting at the RBD of S protein were isolated from mice immunized with inactivated SARS-CoV. Both 1A5 and 2C5 possessed potent neutralizing activities, although they directed against distinct conformation-dependant epitopes as shown by ELISA and binding competition assay. We further demonstrated that 2C5, but not 1A5, was able to block binding of the RBD to angiotensin-converting enzyme 2 (ACE2), the functional receptor on targeted cells. These data provide important information for understanding the antigenicity and immunogenicity of SARS-CoV and for designing SARS vaccines.</p>
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<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Babcock, G J" uniqKey="Babcock G">G.J. Babcock</name>
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<author><name sortKey="Esshaki, D J" uniqKey="Esshaki D">D.J. Esshaki</name>
</author>
<author><name sortKey="Thomas, W D" uniqKey="Thomas W">W.D. Thomas</name>
</author>
<author><name sortKey="Ambrosino, D M" uniqKey="Ambrosino D">D.M. Ambrosino</name>
</author>
</analytic>
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<biblStruct><analytic><author><name sortKey="Bisht, H" uniqKey="Bisht H">H. Bisht</name>
</author>
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</TEI>
<affiliations><list><country><li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region><li>État de New York</li>
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<settlement><li>Pékin</li>
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<tree><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>
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<name sortKey="Liu, Shuwen" sort="Liu, Shuwen" uniqKey="Liu S" first="Shuwen" last="Liu">Shuwen Liu</name>
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<country name="République populaire de Chine"><noRegion><name sortKey="Zhu, Qingyu" sort="Zhu, Qingyu" uniqKey="Zhu Q" first="Qingyu" last="Zhu">Qingyu Zhu</name>
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<name sortKey="Li, Jiaming" sort="Li, Jiaming" uniqKey="Li J" first="Jiaming" last="Li">Jiaming Li</name>
<name sortKey="Yang, Baoan" sort="Yang, Baoan" uniqKey="Yang B" first="Baoan" last="Yang">Baoan Yang</name>
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</record>
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