Human monoclonal antibodies against highly conserved HR1 and HR2 domains of the SARS-CoV spike protein are more broadly neutralizing.
Identifieur interne : 001D12 ( Main/Exploration ); précédent : 001D11; suivant : 001D13Human monoclonal antibodies against highly conserved HR1 and HR2 domains of the SARS-CoV spike protein are more broadly neutralizing.
Auteurs : Hatem A. Elshabrawy [États-Unis] ; Melissa M. Coughlin ; Susan C. Baker ; Bellur S. PrabhakarSource :
- PloS one [ 1932-6203 ] ; 2012.
Descripteurs français
- KwdFr :
- Affinité des anticorps, Anticorps antiviraux (pharmacologie), Anticorps neutralisants (pharmacologie), Cartographie épitopique, Cellules HEK293, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (antagonistes et inhibiteurs), Glycoprotéines membranaires (génétique), Glycoprotéines membranaires (immunologie), Humains, Liaison aux protéines, Protéines de l'enveloppe virale (antagonistes et inhibiteurs), Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (immunologie), Protéines recombinantes (antagonistes et inhibiteurs), Protéines recombinantes (génétique), Protéines recombinantes (immunologie), Réactions croisées, Sites de fixation des anticorps, Spécificité des anticorps, Structure tertiaire des protéines, Syndrome respiratoire aigu sévère (), Syndrome respiratoire aigu sévère (immunologie), Tests de neutralisation, Transfection, Virus du SRAS (), Virus du SRAS (génétique), Virus du SRAS (immunologie).
- MESH :
- antagonistes et inhibiteurs : Glycoprotéines membranaires, Protéines de l'enveloppe virale, Protéines recombinantes.
- génétique : Glycoprotéines membranaires, Protéines de l'enveloppe virale, Protéines recombinantes, Virus du SRAS.
- immunologie : Glycoprotéines membranaires, Protéines de l'enveloppe virale, Protéines recombinantes, Syndrome respiratoire aigu sévère, Virus du SRAS.
- pharmacologie : Anticorps antiviraux, Anticorps neutralisants.
- Affinité des anticorps, Cartographie épitopique, Cellules HEK293, Glycoprotéine de spicule des coronavirus, Humains, Liaison aux protéines, Réactions croisées, Sites de fixation des anticorps, Spécificité des anticorps, Structure tertiaire des protéines, Syndrome respiratoire aigu sévère, Tests de neutralisation, Transfection, Virus du SRAS.
English descriptors
- KwdEn :
- Antibodies, Neutralizing (pharmacology), Antibodies, Viral (pharmacology), Antibody Affinity, Antibody Specificity, Binding Sites, Antibody, Cross Reactions, Epitope Mapping, HEK293 Cells, Humans, Membrane Glycoproteins (antagonists & inhibitors), Membrane Glycoproteins (genetics), Membrane Glycoproteins (immunology), Neutralization Tests, Protein Binding, Protein Structure, Tertiary, Recombinant Proteins (antagonists & inhibitors), Recombinant Proteins (genetics), Recombinant Proteins (immunology), SARS Virus (drug effects), SARS Virus (genetics), SARS Virus (immunology), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (prevention & control), Spike Glycoprotein, Coronavirus, Transfection, Viral Envelope Proteins (antagonists & inhibitors), Viral Envelope Proteins (genetics), Viral Envelope Proteins (immunology).
- MESH :
- chemical , antagonists & inhibitors : Membrane Glycoproteins, Recombinant Proteins, Viral Envelope Proteins.
- chemical , genetics : Membrane Glycoproteins, Recombinant Proteins, Viral Envelope Proteins.
- chemical , immunology : Membrane Glycoproteins, Recombinant Proteins, Viral Envelope Proteins.
- chemical , pharmacology : Antibodies, Neutralizing, Antibodies, Viral.
- drug effects : SARS Virus.
- genetics : SARS Virus.
- immunology : SARS Virus, Severe Acute Respiratory Syndrome.
- prevention & control : Severe Acute Respiratory Syndrome.
- Antibody Affinity, Antibody Specificity, Binding Sites, Antibody, Cross Reactions, Epitope Mapping, HEK293 Cells, Humans, Neutralization Tests, Protein Binding, Protein Structure, Tertiary, Spike Glycoprotein, Coronavirus, Transfection.
Abstract
Immune sera from convalescent patients have been shown to be effective in the treatment of patients infected with Severe Acute Respiratory Syndrome Virus (SARS-CoV) making passive immune therapy with human monoclonal antibodies an attractive treatment strategy for SARS. Previously, using Xenomouse (Amgen British Columbia Inc), we produced a panel of neutralizing Human monoclonal antibodies (HmAbs) that could specifically bind to the ectodomain of the SARS-CoV spike (S) glycoprotein. Some of the HmAbs were S1 domain specific, while some were not. In this study, we describe non-S1 binding neutralizing HmAbs that can specifically bind to the conserved S2 domain of the S protein. However, unlike the S1 specific HmAbs, the S2 specific HmAbs can neutralize pseudotyped viruses expressing different S proteins containing receptor binding domain sequences of various clinical isolates. These data indicate that HmAbs which bind to conserved regions of the S protein are more suitable for conferring protection against a wide range of SARS-CoV variants and have implications for generating therapeutic antibodies or subunit vaccines against other enveloped viruses.
DOI: 10.1371/journal.pone.0050366
PubMed: 23185609
Affiliations:
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Le document en format XML
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<term>Antibodies, Viral (pharmacology)</term>
<term>Antibody Affinity</term>
<term>Antibody Specificity</term>
<term>Binding Sites, Antibody</term>
<term>Cross Reactions</term>
<term>Epitope Mapping</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Membrane Glycoproteins (antagonists & inhibitors)</term>
<term>Membrane Glycoproteins (genetics)</term>
<term>Membrane Glycoproteins (immunology)</term>
<term>Neutralization Tests</term>
<term>Protein Binding</term>
<term>Protein Structure, Tertiary</term>
<term>Recombinant Proteins (antagonists & inhibitors)</term>
<term>Recombinant Proteins (genetics)</term>
<term>Recombinant Proteins (immunology)</term>
<term>SARS Virus (drug effects)</term>
<term>SARS Virus (genetics)</term>
<term>SARS Virus (immunology)</term>
<term>Severe Acute Respiratory Syndrome (immunology)</term>
<term>Severe Acute Respiratory Syndrome (prevention & control)</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Transfection</term>
<term>Viral Envelope Proteins (antagonists & inhibitors)</term>
<term>Viral Envelope Proteins (genetics)</term>
<term>Viral Envelope Proteins (immunology)</term>
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<keywords scheme="KwdFr" xml:lang="fr"><term>Affinité des anticorps</term>
<term>Anticorps antiviraux (pharmacologie)</term>
<term>Anticorps neutralisants (pharmacologie)</term>
<term>Cartographie épitopique</term>
<term>Cellules HEK293</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires (antagonistes et inhibiteurs)</term>
<term>Glycoprotéines membranaires (génétique)</term>
<term>Glycoprotéines membranaires (immunologie)</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Protéines de l'enveloppe virale (antagonistes et inhibiteurs)</term>
<term>Protéines de l'enveloppe virale (génétique)</term>
<term>Protéines de l'enveloppe virale (immunologie)</term>
<term>Protéines recombinantes (antagonistes et inhibiteurs)</term>
<term>Protéines recombinantes (génétique)</term>
<term>Protéines recombinantes (immunologie)</term>
<term>Réactions croisées</term>
<term>Sites de fixation des anticorps</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>Tests de neutralisation</term>
<term>Transfection</term>
<term>Virus du SRAS ()</term>
<term>Virus du SRAS (génétique)</term>
<term>Virus du SRAS (immunologie)</term>
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<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Membrane Glycoproteins</term>
<term>Recombinant Proteins</term>
<term>Viral Envelope Proteins</term>
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<term>Recombinant Proteins</term>
<term>Viral Envelope Proteins</term>
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<term>Recombinant Proteins</term>
<term>Viral Envelope Proteins</term>
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<term>Antibodies, Viral</term>
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<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Glycoprotéines membranaires</term>
<term>Protéines de l'enveloppe virale</term>
<term>Protéines recombinantes</term>
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<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>SARS Virus</term>
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<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term>
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<term>Protéines recombinantes</term>
<term>Virus du SRAS</term>
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<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Glycoprotéines membranaires</term>
<term>Protéines de l'enveloppe virale</term>
<term>Protéines recombinantes</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>SARS Virus</term>
<term>Severe Acute Respiratory Syndrome</term>
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<term>Anticorps neutralisants</term>
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</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Antibody Affinity</term>
<term>Antibody Specificity</term>
<term>Binding Sites, Antibody</term>
<term>Cross Reactions</term>
<term>Epitope Mapping</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Neutralization Tests</term>
<term>Protein Binding</term>
<term>Protein Structure, Tertiary</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Transfection</term>
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<term>Cartographie épitopique</term>
<term>Cellules HEK293</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Réactions croisées</term>
<term>Sites de fixation des anticorps</term>
<term>Spécificité des anticorps</term>
<term>Structure tertiaire des protéines</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Tests de neutralisation</term>
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<front><div type="abstract" xml:lang="en">Immune sera from convalescent patients have been shown to be effective in the treatment of patients infected with Severe Acute Respiratory Syndrome Virus (SARS-CoV) making passive immune therapy with human monoclonal antibodies an attractive treatment strategy for SARS. Previously, using Xenomouse (Amgen British Columbia Inc), we produced a panel of neutralizing Human monoclonal antibodies (HmAbs) that could specifically bind to the ectodomain of the SARS-CoV spike (S) glycoprotein. Some of the HmAbs were S1 domain specific, while some were not. In this study, we describe non-S1 binding neutralizing HmAbs that can specifically bind to the conserved S2 domain of the S protein. However, unlike the S1 specific HmAbs, the S2 specific HmAbs can neutralize pseudotyped viruses expressing different S proteins containing receptor binding domain sequences of various clinical isolates. These data indicate that HmAbs which bind to conserved regions of the S protein are more suitable for conferring protection against a wide range of SARS-CoV variants and have implications for generating therapeutic antibodies or subunit vaccines against other enveloped viruses.</div>
</front>
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<tree><noCountry><name sortKey="Baker, Susan C" sort="Baker, Susan C" uniqKey="Baker S" first="Susan C" last="Baker">Susan C. Baker</name>
<name sortKey="Coughlin, Melissa M" sort="Coughlin, Melissa M" uniqKey="Coughlin M" first="Melissa M" last="Coughlin">Melissa M. Coughlin</name>
<name sortKey="Prabhakar, Bellur S" sort="Prabhakar, Bellur S" uniqKey="Prabhakar B" first="Bellur S" last="Prabhakar">Bellur S. Prabhakar</name>
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<country name="États-Unis"><region name="Illinois"><name sortKey="Elshabrawy, Hatem A" sort="Elshabrawy, Hatem A" uniqKey="Elshabrawy H" first="Hatem A" last="Elshabrawy">Hatem A. Elshabrawy</name>
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