Evaluation of Human Monoclonal Antibody 80R for Immunoprophylaxis of Severe Acute Respiratory Syndrome by an Animal Study, Epitope Mapping, and Analysis of Spike Variants
Identifieur interne : 004842 ( Main/Exploration ); précédent : 004841; suivant : 004843Evaluation of Human Monoclonal Antibody 80R for Immunoprophylaxis of Severe Acute Respiratory Syndrome by an Animal Study, Epitope Mapping, and Analysis of Spike Variants
Auteurs : Jianhua Sui ; Wenhui Li ; Anjeanette Roberts ; Leslie J. Matthews ; Akikazu Murakami ; Leatrice Vogel ; Swee Kee Wong ; Kanta Subbarao ; Michael Farzan ; Wayne A. MarascoSource :
- Journal of Virology [ 0022-538X ] ; 2005.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (administration et posologie), Anticorps antiviraux (immunologie), Anticorps monoclonaux (administration et posologie), Anticorps monoclonaux (immunologie), Cartographie épitopique, Escherichia coli (métabolisme), Femelle, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (), Glycoprotéines membranaires (génétique), Glycoprotéines membranaires (immunologie), Génotype, Humains, Immunisation passive, Immunoglobuline G (administration et posologie), Immunoglobuline G (immunologie), Modèles animaux de maladie humaine, Protéines de l'enveloppe virale (), Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (immunologie), Récepteurs viraux (antagonistes et inhibiteurs), Récepteurs viraux (métabolisme), Souris, Souris de lignée BALB C, Substitution d'acide aminé, Syndrome respiratoire aigu sévère (), Syndrome respiratoire aigu sévère (virologie), Vaccins antiviraux (administration et posologie), Vaccins antiviraux (immunologie), Virus du SRAS (génétique), Virus du SRAS (immunologie), Virus du SRAS (isolement et purification).
- MESH :
- administration et posologie : Anticorps antiviraux, Anticorps monoclonaux, Immunoglobuline G, Vaccins antiviraux.
- antagonistes et inhibiteurs : Récepteurs viraux.
- génétique : Glycoprotéines membranaires, Protéines de l'enveloppe virale, Virus du SRAS.
- immunologie : Anticorps antiviraux, Anticorps monoclonaux, Glycoprotéines membranaires, Immunoglobuline G, Protéines de l'enveloppe virale, Vaccins antiviraux, Virus du SRAS.
- isolement et purification : Virus du SRAS.
- métabolisme : Escherichia coli, Récepteurs viraux.
- virologie : Syndrome respiratoire aigu sévère.
- Animaux, Cartographie épitopique, Femelle, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Génotype, Humains, Immunisation passive, Modèles animaux de maladie humaine, Protéines de l'enveloppe virale, Souris, Souris de lignée BALB C, Substitution d'acide aminé, Syndrome respiratoire aigu sévère.
English descriptors
- KwdEn :
- Amino Acid Substitution, Animals, Antibodies, Monoclonal (administration & dosage), Antibodies, Monoclonal (immunology), Antibodies, Viral (administration & dosage), Antibodies, Viral (immunology), Disease Models, Animal, Epitope Mapping, Escherichia coli (metabolism), Female, Genotype, Humans, Immunization, Passive, Immunoglobulin G (administration & dosage), Immunoglobulin G (immunology), Membrane Glycoproteins (chemistry), Membrane Glycoproteins (genetics), Membrane Glycoproteins (immunology), Mice, Mice, Inbred BALB C, Receptors, Virus (antagonists & inhibitors), Receptors, Virus (metabolism), SARS Virus (genetics), SARS Virus (immunology), SARS Virus (isolation & purification), 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 (administration & dosage), Viral Vaccines (immunology).
- MESH :
- chemical , administration & dosage : Antibodies, Monoclonal, Antibodies, Viral, Immunoglobulin G, Viral Vaccines.
- chemical , antagonists & inhibitors : Receptors, Virus.
- chemical , chemistry : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , genetics : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , immunology : Antibodies, Monoclonal, Antibodies, Viral, Immunoglobulin G, Membrane Glycoproteins, Viral Envelope Proteins, Viral Vaccines.
- genetics : SARS Virus.
- immunology : SARS Virus.
- isolation & purification : SARS Virus.
- metabolism : Escherichia coli, Receptors, Virus.
- prevention & control : Severe Acute Respiratory Syndrome.
- virology : Severe Acute Respiratory Syndrome.
- Amino Acid Substitution, Animals, Disease Models, Animal, Epitope Mapping, Female, Genotype, Humans, Immunization, Passive, Mice, Mice, Inbred BALB C, Spike Glycoprotein, Coronavirus.
Abstract
In this report, the antiviral activity of 80R immunoglobulin G1 (IgG1), a human monoclonal antibody against severe acute respiratory syndrome coronavirus (SARS-CoV) spike (S) protein that acts as a viral entry inhibitor in vitro, was investigated in vivo in a mouse model. When 80R IgG1 was given prophylactically to mice at doses therapeutically achievable in humans, viral replication was reduced by more than 4 orders of magnitude to below assay limits. The essential core region of S protein required for 80R binding was identified as a conformationally sensitive fragment (residues 324 to 503) that overlaps the receptor ACE2-binding domain. Amino acids critical for 80R binding were identified. In addition, the effects of various 80R-binding domain amino acid substitutions which occur in SARS-like-CoV from civet cats, and which evolved during the 2002/2003 outbreak and in a 2003/2004 Guangdong index patient, were analyzed. The results demonstrated that the vast majority of SARS-CoVs are sensitive to 80R. We propose that by establishing the susceptibility and resistance profiles of newly emerging SARS-CoVs through early S1 genotyping of the core 180-amino-acid neutralizing epitope of 80R, an effective immunoprophylaxis strategy with 80R should be possible in an outbreak setting. Our study also cautions that for any prophylaxis strategy based on neutralizing antibody responses, whether by passive or active immunization, a genotyping monitor will be necessary for effective use.
Url:
DOI: 10.1128/JVI.79.10.5900-5906.2005
PubMed: 15857975
PubMed Central: 1091676
Affiliations:
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Le document en format XML
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Marasco</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Virology</title><idno type="ISSN">0022-538X</idno><idno type="eISSN">1098-5514</idno><imprint><date when="2005">2005</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Substitution</term><term>Animals</term><term>Antibodies, Monoclonal (administration & dosage)</term><term>Antibodies, Monoclonal (immunology)</term><term>Antibodies, Viral (administration & dosage)</term><term>Antibodies, Viral (immunology)</term><term>Disease Models, Animal</term><term>Epitope Mapping</term><term>Escherichia coli (metabolism)</term><term>Female</term><term>Genotype</term><term>Humans</term><term>Immunization, Passive</term><term>Immunoglobulin G (administration & dosage)</term><term>Immunoglobulin G (immunology)</term><term>Membrane Glycoproteins (chemistry)</term><term>Membrane Glycoproteins (genetics)</term><term>Membrane Glycoproteins (immunology)</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Receptors, Virus (antagonists & inhibitors)</term><term>Receptors, Virus (metabolism)</term><term>SARS Virus (genetics)</term><term>SARS Virus (immunology)</term><term>SARS Virus (isolation & purification)</term><term>Severe Acute Respiratory Syndrome (prevention & control)</term><term>Severe Acute Respiratory Syndrome (virology)</term><term>Spike Glycoprotein, Coronavirus</term><term>Viral Envelope Proteins (chemistry)</term><term>Viral Envelope Proteins (genetics)</term><term>Viral Envelope Proteins (immunology)</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 (administration et posologie)</term><term>Anticorps antiviraux (immunologie)</term><term>Anticorps monoclonaux (administration et posologie)</term><term>Anticorps monoclonaux (immunologie)</term><term>Cartographie épitopique</term><term>Escherichia coli (métabolisme)</term><term>Femelle</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires ()</term><term>Glycoprotéines membranaires (génétique)</term><term>Glycoprotéines membranaires (immunologie)</term><term>Génotype</term><term>Humains</term><term>Immunisation passive</term><term>Immunoglobuline G (administration et posologie)</term><term>Immunoglobuline G (immunologie)</term><term>Modèles animaux de maladie humaine</term><term>Protéines de l'enveloppe virale ()</term><term>Protéines de l'enveloppe virale (génétique)</term><term>Protéines de l'enveloppe virale (immunologie)</term><term>Récepteurs viraux (antagonistes et inhibiteurs)</term><term>Récepteurs viraux (métabolisme)</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Substitution d'acide aminé</term><term>Syndrome respiratoire aigu sévère ()</term><term>Syndrome respiratoire aigu sévère (virologie)</term><term>Vaccins antiviraux (administration et posologie)</term><term>Vaccins antiviraux (immunologie)</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (immunologie)</term><term>Virus du SRAS (isolement et purification)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Antibodies, Viral</term><term>Immunoglobulin G</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Receptors, Virus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Antibodies, Viral</term><term>Immunoglobulin G</term><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps monoclonaux</term><term>Immunoglobuline G</term><term>Vaccins antiviraux</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Récepteurs viraux</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps 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sévère</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Substitution</term><term>Animals</term><term>Disease Models, Animal</term><term>Epitope Mapping</term><term>Female</term><term>Genotype</term><term>Humans</term><term>Immunization, Passive</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cartographie épitopique</term><term>Femelle</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires</term><term>Génotype</term><term>Humains</term><term>Immunisation passive</term><term>Modèles animaux de maladie humaine</term><term>Protéines de l'enveloppe virale</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Substitution d'acide aminé</term><term>Syndrome respiratoire aigu sévère</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>In this report, the antiviral activity of 80R immunoglobulin G1 (IgG1), a human monoclonal antibody against severe acute respiratory syndrome coronavirus (SARS-CoV) spike (S) protein that acts as a viral entry inhibitor in vitro, was investigated in vivo in a mouse model. When 80R IgG1 was given prophylactically to mice at doses therapeutically achievable in humans, viral replication was reduced by more than 4 orders of magnitude to below assay limits. The essential core region of S protein required for 80R binding was identified as a conformationally sensitive fragment (residues 324 to 503) that overlaps the receptor ACE2-binding domain. Amino acids critical for 80R binding were identified. In addition, the effects of various 80R-binding domain amino acid substitutions which occur in SARS-like-CoV from civet cats, and which evolved during the 2002/2003 outbreak and in a 2003/2004 Guangdong index patient, were analyzed. The results demonstrated that the vast majority of SARS-CoVs are sensitive to 80R. We propose that by establishing the susceptibility and resistance profiles of newly emerging SARS-CoVs through early S1 genotyping of the core 180-amino-acid neutralizing epitope of 80R, an effective immunoprophylaxis strategy with 80R should be possible in an outbreak setting. Our study also cautions that for any prophylaxis strategy based on neutralizing antibody responses, whether by passive or active immunization, a genotyping monitor will be necessary for effective use.</p></div></front></TEI><affiliations><list></list><tree><noCountry><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="Murakami, Akikazu" sort="Murakami, Akikazu" uniqKey="Murakami A" first="Akikazu" last="Murakami">Akikazu Murakami</name><name sortKey="Roberts, Anjeanette" sort="Roberts, Anjeanette" uniqKey="Roberts A" first="Anjeanette" last="Roberts">Anjeanette Roberts</name><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name><name sortKey="Sui, Jianhua" sort="Sui, Jianhua" uniqKey="Sui J" first="Jianhua" last="Sui">Jianhua Sui</name><name sortKey="Vogel, Leatrice" sort="Vogel, Leatrice" uniqKey="Vogel L" first="Leatrice" last="Vogel">Leatrice Vogel</name><name sortKey="Wong, Swee Kee" sort="Wong, Swee Kee" uniqKey="Wong S" first="Swee Kee" last="Wong">Swee Kee Wong</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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