Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association.
Identifieur interne : 005205 ( Main/Exploration ); précédent : 005204; suivant : 005206Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association.
Auteurs : Jianhua Sui [États-Unis] ; Wenhui Li ; Akikazu Murakami ; Azaibi Tamin ; Leslie J. Matthews ; Swee Kee Wong ; Michael J. Moore ; Aimee St Clair Tallarico ; Mobolaji Olurinde ; Hyeryun Choe ; Larry J. Anderson ; William J. Bellini ; Michael Farzan ; Wayne A. MarascoSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2004.
Descripteurs français
- KwdFr :
- Alignement de séquences, Anticorps monoclonaux, Banque de gènes, Cellules géantes (immunologie), Chaines lourdes des immunoglobulines (), Chaines lourdes des immunoglobulines (génétique), Chaines légères des immunoglobulines (), Chaines légères des immunoglobulines (génétique), Données de séquences moléculaires, Humains, Immunoglobuline G (génétique), Immunoglobuline G (immunologie), Immunoglobuline G (isolement et purification), Récepteurs viraux (immunologie), Similitude de séquences d'acides aminés, Syndrome respiratoire aigu sévère (immunologie), Séquence d'acides aminés, Tests de neutralisation, Virus du SRAS (immunologie), Virus du SRAS (pathogénicité).
- MESH :
- génétique : Chaines lourdes des immunoglobulines, Chaines légères des immunoglobulines, Immunoglobuline G.
- immunologie : Cellules géantes, Immunoglobuline G, Récepteurs viraux, Syndrome respiratoire aigu sévère, Virus du SRAS.
- isolement et purification : Immunoglobuline G.
- pathogénicité : Virus du SRAS.
- Alignement de séquences, Anticorps monoclonaux, Banque de gènes, Chaines lourdes des immunoglobulines, Chaines légères des immunoglobulines, Données de séquences moléculaires, Humains, Similitude de séquences d'acides aminés, Séquence d'acides aminés, Tests de neutralisation.
English descriptors
- KwdEn :
- Amino Acid Sequence, Antibodies, Monoclonal, Gene Library, Giant Cells (immunology), Humans, Immunoglobulin G (genetics), Immunoglobulin G (immunology), Immunoglobulin G (isolation & purification), Immunoglobulin Heavy Chains (chemistry), Immunoglobulin Heavy Chains (genetics), Immunoglobulin Light Chains (chemistry), Immunoglobulin Light Chains (genetics), Molecular Sequence Data, Neutralization Tests, Receptors, Virus (immunology), SARS Virus (immunology), SARS Virus (pathogenicity), Sequence Alignment, Sequence Homology, Amino Acid, Severe Acute Respiratory Syndrome (immunology).
- MESH :
- chemical , chemistry : Immunoglobulin Heavy Chains, Immunoglobulin Light Chains.
- chemical , genetics : Immunoglobulin G, Immunoglobulin Heavy Chains, Immunoglobulin Light Chains.
- chemical , immunology : Immunoglobulin G, Receptors, Virus.
- chemical , isolation & purification : Immunoglobulin G.
- chemical : Antibodies, Monoclonal.
- immunology : Giant Cells, SARS Virus, Severe Acute Respiratory Syndrome.
- pathogenicity : SARS Virus.
- Amino Acid Sequence, Gene Library, Humans, Molecular Sequence Data, Neutralization Tests, Sequence Alignment, Sequence Homology, Amino Acid.
Abstract
Effective prophylaxis and antiviral therapies are urgently needed in the event of reemergence of the highly contagious and often fatal severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) infection. We have identified eight recombinant human single-chain variable region fragments (scFvs) against the S1 domain of spike (S) protein of the SARS-CoV from two nonimmune human antibody libraries. One scFv 80R efficiently neutralized SARS-CoV and inhibited syncytia formation between cells expressing the S protein and those expressing the SARS-CoV receptor angiotensin-converting enzyme 2 (ACE2). Mapping of the 80R epitope showed it is located within the N-terminal 261-672 amino acids of S protein and is not glycosylation-dependent. 80R scFv competed with soluble ACE2 for association with the S1 domain and bound S1 with high affinity (equilibrium dissociation constant, Kd=32.3 nM). A human IgG1 form of 80R bound S1 with a 20-fold higher affinity of 1.59 nM comparable to that of ACE2 (Kd=1.70 nM), and neutralized virus 20-fold more efficiently than the 80R scFv. These data suggest that the 80R human monoclonal antibody may be a useful viral entry inhibitor for the emergency prophylaxis and treatment of SARS, and that the ACE2-binding site of S1 could be an attractive target for subunit vaccine and drug development.
DOI: 10.1073/pnas.0307140101
PubMed: 14983044
Affiliations:
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Matthews</name></author><author><name sortKey="Wong, Swee Kee" sort="Wong, Swee Kee" uniqKey="Wong S" first="Swee Kee" last="Wong">Swee Kee Wong</name></author><author><name sortKey="Moore, Michael J" sort="Moore, Michael J" uniqKey="Moore M" first="Michael J" last="Moore">Michael J. Moore</name></author><author><name sortKey="Tallarico, Aimee St Clair" sort="Tallarico, Aimee St Clair" uniqKey="Tallarico A" first="Aimee St Clair" last="Tallarico">Aimee St Clair Tallarico</name></author><author><name sortKey="Olurinde, Mobolaji" sort="Olurinde, Mobolaji" uniqKey="Olurinde M" first="Mobolaji" last="Olurinde">Mobolaji Olurinde</name></author><author><name sortKey="Choe, Hyeryun" sort="Choe, Hyeryun" uniqKey="Choe H" first="Hyeryun" last="Choe">Hyeryun Choe</name></author><author><name sortKey="Anderson, Larry J" sort="Anderson, Larry J" uniqKey="Anderson L" first="Larry J" last="Anderson">Larry J. 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Marasco</name></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><imprint><date when="2004" type="published">2004</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Antibodies, Monoclonal</term><term>Gene Library</term><term>Giant Cells (immunology)</term><term>Humans</term><term>Immunoglobulin G (genetics)</term><term>Immunoglobulin G (immunology)</term><term>Immunoglobulin G (isolation & purification)</term><term>Immunoglobulin Heavy Chains (chemistry)</term><term>Immunoglobulin Heavy Chains (genetics)</term><term>Immunoglobulin Light Chains (chemistry)</term><term>Immunoglobulin Light Chains (genetics)</term><term>Molecular Sequence Data</term><term>Neutralization Tests</term><term>Receptors, Virus (immunology)</term><term>SARS Virus (immunology)</term><term>SARS Virus (pathogenicity)</term><term>Sequence Alignment</term><term>Sequence Homology, Amino Acid</term><term>Severe Acute Respiratory Syndrome (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Alignement de séquences</term><term>Anticorps monoclonaux</term><term>Banque de gènes</term><term>Cellules géantes (immunologie)</term><term>Chaines lourdes des immunoglobulines ()</term><term>Chaines lourdes des immunoglobulines (génétique)</term><term>Chaines légères des immunoglobulines ()</term><term>Chaines légères des immunoglobulines (génétique)</term><term>Données de séquences moléculaires</term><term>Humains</term><term>Immunoglobuline G (génétique)</term><term>Immunoglobuline G (immunologie)</term><term>Immunoglobuline G (isolement et purification)</term><term>Récepteurs viraux (immunologie)</term><term>Similitude de séquences d'acides aminés</term><term>Syndrome respiratoire aigu sévère (immunologie)</term><term>Séquence d'acides aminés</term><term>Tests de neutralisation</term><term>Virus du SRAS (immunologie)</term><term>Virus du SRAS (pathogénicité)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Immunoglobulin Heavy Chains</term><term>Immunoglobulin Light Chains</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Immunoglobulin G</term><term>Immunoglobulin Heavy Chains</term><term>Immunoglobulin Light Chains</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Immunoglobulin G</term><term>Receptors, Virus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="isolation & purification" xml:lang="en"><term>Immunoglobulin G</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Antibodies, Monoclonal</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Chaines lourdes des immunoglobulines</term><term>Chaines légères des immunoglobulines</term><term>Immunoglobuline G</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Cellules géantes</term><term>Immunoglobuline G</term><term>Récepteurs viraux</term><term>Syndrome respiratoire aigu sévère</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Giant Cells</term><term>SARS Virus</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Immunoglobuline G</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Gene Library</term><term>Humans</term><term>Molecular Sequence Data</term><term>Neutralization Tests</term><term>Sequence Alignment</term><term>Sequence Homology, Amino Acid</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Alignement de séquences</term><term>Anticorps monoclonaux</term><term>Banque de gènes</term><term>Chaines lourdes des immunoglobulines</term><term>Chaines légères des immunoglobulines</term><term>Données de séquences moléculaires</term><term>Humains</term><term>Similitude de séquences d'acides aminés</term><term>Séquence d'acides aminés</term><term>Tests de neutralisation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Effective prophylaxis and antiviral therapies are urgently needed in the event of reemergence of the highly contagious and often fatal severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) infection. We have identified eight recombinant human single-chain variable region fragments (scFvs) against the S1 domain of spike (S) protein of the SARS-CoV from two nonimmune human antibody libraries. One scFv 80R efficiently neutralized SARS-CoV and inhibited syncytia formation between cells expressing the S protein and those expressing the SARS-CoV receptor angiotensin-converting enzyme 2 (ACE2). Mapping of the 80R epitope showed it is located within the N-terminal 261-672 amino acids of S protein and is not glycosylation-dependent. 80R scFv competed with soluble ACE2 for association with the S1 domain and bound S1 with high affinity (equilibrium dissociation constant, Kd=32.3 nM). A human IgG1 form of 80R bound S1 with a 20-fold higher affinity of 1.59 nM comparable to that of ACE2 (Kd=1.70 nM), and neutralized virus 20-fold more efficiently than the 80R scFv. These data suggest that the 80R human monoclonal antibody may be a useful viral entry inhibitor for the emergency prophylaxis and treatment of SARS, and that the ACE2-binding site of S1 could be an attractive target for subunit vaccine and drug development.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Massachusetts</li></region></list><tree><noCountry><name sortKey="Anderson, Larry J" sort="Anderson, Larry J" uniqKey="Anderson L" first="Larry J" last="Anderson">Larry J. Anderson</name><name sortKey="Bellini, William J" sort="Bellini, William J" uniqKey="Bellini W" first="William J" last="Bellini">William J. Bellini</name><name sortKey="Choe, Hyeryun" sort="Choe, Hyeryun" uniqKey="Choe H" first="Hyeryun" last="Choe">Hyeryun Choe</name><name sortKey="Farzan, Michael" sort="Farzan, Michael" uniqKey="Farzan M" first="Michael" last="Farzan">Michael Farzan</name><name sortKey="Li, Wenhui" sort="Li, Wenhui" uniqKey="Li W" first="Wenhui" last="Li">Wenhui Li</name><name sortKey="Marasco, Wayne A" sort="Marasco, Wayne A" uniqKey="Marasco W" first="Wayne A" last="Marasco">Wayne A. Marasco</name><name sortKey="Matthews, Leslie J" sort="Matthews, Leslie J" uniqKey="Matthews L" first="Leslie J" last="Matthews">Leslie J. Matthews</name><name sortKey="Moore, Michael J" sort="Moore, Michael J" uniqKey="Moore M" first="Michael J" last="Moore">Michael J. Moore</name><name sortKey="Murakami, Akikazu" sort="Murakami, Akikazu" uniqKey="Murakami A" first="Akikazu" last="Murakami">Akikazu Murakami</name><name sortKey="Olurinde, Mobolaji" sort="Olurinde, Mobolaji" uniqKey="Olurinde M" first="Mobolaji" last="Olurinde">Mobolaji Olurinde</name><name sortKey="Tallarico, Aimee St Clair" sort="Tallarico, Aimee St Clair" uniqKey="Tallarico A" first="Aimee St Clair" last="Tallarico">Aimee St Clair Tallarico</name><name sortKey="Tamin, Azaibi" sort="Tamin, Azaibi" uniqKey="Tamin A" first="Azaibi" last="Tamin">Azaibi Tamin</name><name sortKey="Wong, Swee Kee" sort="Wong, Swee Kee" uniqKey="Wong S" first="Swee Kee" last="Wong">Swee Kee Wong</name></noCountry><country name="États-Unis"><region name="Massachusetts"><name sortKey="Sui, Jianhua" sort="Sui, Jianhua" uniqKey="Sui J" first="Jianhua" last="Sui">Jianhua Sui</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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