Development and Characterization of a Severe Acute Respiratory Syndrome—Associated Coronavirus—Neutralizing Human Monoclonal Antibody That Provides Effective Immunoprophylaxis in Mice
Identifieur interne : 004999 ( Main/Exploration ); précédent : 004998; suivant : 004A00Development and Characterization of a Severe Acute Respiratory Syndrome—Associated Coronavirus—Neutralizing Human Monoclonal Antibody That Provides Effective Immunoprophylaxis in Mice
Auteurs : Thomas C. Greenough ; Gregory J. Babcock ; Anjeanette Roberts [États-Unis] ; Hector J. Hernandez ; William D. Thomas ; Jennifer A. Coccia ; Robert F. Graziano [États-Unis] ; Mohan Srinivasan [États-Unis] ; Israel Lowy [États-Unis] ; Robert W. Finberg ; Kanta Subbarao [États-Unis] ; Leatrice Vogel [États-Unis] ; Mohan Somasundaran ; Katherine Luzuriaga ; John L. Sullivan ; Donna M. Ambrosino [États-Unis]Source :
- The Journal of Infectious Diseases [ 0022-1899 ] ; 2005.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (usage thérapeutique), Anticorps monoclonaux (usage thérapeutique), Cartographie épitopique, Cellules cultivées, Femelle, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (immunologie), Immunisation passive, Liaison aux protéines, Modèles animaux de maladie humaine, Poumon (virologie), Protéines de l'enveloppe virale (immunologie), Souris, Souris de lignée BALB C, Souris transgéniques, Syndrome respiratoire aigu sévère (), Tests de neutralisation, Virus du SRAS (immunologie), Épitopes (immunologie).
- MESH :
- immunologie : Glycoprotéines membranaires, Protéines de l'enveloppe virale, Virus du SRAS, Épitopes.
- usage thérapeutique : Anticorps antiviraux, Anticorps monoclonaux.
- virologie : Poumon.
- Animaux, Cartographie épitopique, Cellules cultivées, Femelle, Glycoprotéine de spicule des coronavirus, Immunisation passive, Liaison aux protéines, Modèles animaux de maladie humaine, Souris, Souris de lignée BALB C, Souris transgéniques, Syndrome respiratoire aigu sévère, Tests de neutralisation.
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
- Animals, Antibodies, Monoclonal (therapeutic use), Antibodies, Viral (therapeutic use), Cells, Cultured, Disease Models, Animal, Epitope Mapping, Epitopes (immunology), Female, Human, Immunization, Passive, Immunoprophylaxis, Infection, Lung (virology), Membrane Glycoproteins (immunology), Mice, Mice, Inbred BALB C, Mice, Transgenic, Microbiology, Monoclonal antibody, Mouse, Neutralization Tests, Neutralizing antibody, Protein Binding, SARS Virus (immunology), Severe Acute Respiratory Syndrome (prevention & control), Severe acute respiratory syndrome, Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (immunology).
- MESH :
- chemical , immunology : Epitopes, Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , therapeutic use : Antibodies, Monoclonal, Antibodies, Viral.
- immunology : SARS Virus.
- prevention & control : Severe Acute Respiratory Syndrome.
- virology : Lung.
- Animals, Cells, Cultured, Disease Models, Animal, Epitope Mapping, Female, Immunization, Passive, Mice, Mice, Inbred BALB C, Mice, Transgenic, Neutralization Tests, Protein Binding, Spike Glycoprotein, Coronavirus.
Abstract
Background. Severe acute respiratory syndrome (SARS) remains a significant public health concern after the epidemic in 2003. Human monoclonal antibodies (MAbs) that neutralize SARS-associated coronavirus (SARSCoV) could provide protection for exposed individuals. Methods. Transgenic mice with human immunoglobulin genes were immunized with the recombinant major surface (S) glycoprotein ectodomain of SARS-CoV. Epitopes of 2 neutralizing MAbs derived from these mice were mapped and evaluated in a murine model of SARS-CoV infection. Results. Both MAbs bound to S glycoprotein expressed on transfected cells but differed in their ability to block binding of S glycoprotein to Vero E6 cells. Immunoprecipitation analysis revealed 2 antibody-binding epitopes: one MAb (201) bound within the receptor-binding domain at aa 490–510, and the other MAb (68) bound externally to the domain at aa 130–150. Mice that received 40 mg/kg of either MAb prior to challenge with SARS-CoV were completely protected from virus replication in the lungs, and doses as low as 1.6 mg/kg offered significant protection. Conclusions. Two neutralizing epitopes were defined for MAbs to SARS-CoV S glycoprotein. Antibodies to both epitopes protected mice against SARS-CoV challenge. Clinical trials are planned to test MAb 201, a fully human MAb specific for the epitope within the receptor-binding region.
Url:
- https://api.istex.fr/ark:/67375/HXZ-HLL4XB7B-B/fulltext.pdf
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110081
DOI: 10.1086/427242
Affiliations:
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Finberg</name><affiliation><wicri:noCountry code="subField">Worcester</wicri:noCountry></affiliation></author><author><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Vogel, Leatrice" sort="Vogel, Leatrice" uniqKey="Vogel L" first="Leatrice" last="Vogel">Leatrice Vogel</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Somasundaran, Mohan" sort="Somasundaran, Mohan" uniqKey="Somasundaran M" first="Mohan" last="Somasundaran">Mohan Somasundaran</name><affiliation><wicri:noCountry code="subField">Worcester</wicri:noCountry></affiliation></author><author><name sortKey="Luzuriaga, Katherine" sort="Luzuriaga, Katherine" uniqKey="Luzuriaga K" first="Katherine" last="Luzuriaga">Katherine Luzuriaga</name><affiliation><wicri:noCountry code="subField">Worcester</wicri:noCountry></affiliation></author><author><name sortKey="Sullivan, John L" sort="Sullivan, John L" uniqKey="Sullivan J" first="John L." last="Sullivan">John L. Sullivan</name><affiliation><wicri:noCountry code="subField">Worcester</wicri:noCountry></affiliation></author><author><name sortKey="Ambrosino, Donna M" sort="Ambrosino, Donna M" uniqKey="Ambrosino D" first="Donna M." last="Ambrosino">Donna M. Ambrosino</name><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">États-Unis</country></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Reprints or correspondence: Dr. Donna M. Ambrosino, Massachusetts Biologic Laboratories, 305 South St., Jamaica Plain</wicri:cityArea></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">The Journal of Infectious Diseases</title><title level="j" type="abbrev">The Journal of Infectious Diseases</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><publisher>The University of Chicago Press</publisher><date type="published">2005</date><biblScope unit="vol">191</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="507">507</biblScope><biblScope unit="page" to="514">514</biblScope></imprint><idno type="ISSN">0022-1899</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-1899</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Monoclonal (therapeutic use)</term><term>Antibodies, Viral (therapeutic use)</term><term>Cells, Cultured</term><term>Disease Models, Animal</term><term>Epitope Mapping</term><term>Epitopes (immunology)</term><term>Female</term><term>Human</term><term>Immunization, Passive</term><term>Immunoprophylaxis</term><term>Infection</term><term>Lung (virology)</term><term>Membrane Glycoproteins (immunology)</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mice, Transgenic</term><term>Microbiology</term><term>Monoclonal antibody</term><term>Mouse</term><term>Neutralization Tests</term><term>Neutralizing antibody</term><term>Protein Binding</term><term>SARS Virus (immunology)</term><term>Severe Acute Respiratory Syndrome (prevention & control)</term><term>Severe acute respiratory syndrome</term><term>Spike Glycoprotein, Coronavirus</term><term>Viral Envelope Proteins (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anticorps antiviraux (usage thérapeutique)</term><term>Anticorps monoclonaux (usage thérapeutique)</term><term>Cartographie épitopique</term><term>Cellules cultivées</term><term>Femelle</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires (immunologie)</term><term>Immunisation passive</term><term>Liaison aux protéines</term><term>Modèles animaux de maladie humaine</term><term>Poumon (virologie)</term><term>Protéines de l'enveloppe virale (immunologie)</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Souris transgéniques</term><term>Syndrome respiratoire aigu sévère ()</term><term>Tests de neutralisation</term><term>Virus du SRAS (immunologie)</term><term>Épitopes (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Epitopes</term><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term><term>Virus du SRAS</term><term>Épitopes</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps monoclonaux</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cells, Cultured</term><term>Disease Models, Animal</term><term>Epitope Mapping</term><term>Female</term><term>Immunization, Passive</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mice, Transgenic</term><term>Neutralization Tests</term><term>Protein Binding</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cartographie épitopique</term><term>Cellules cultivées</term><term>Femelle</term><term>Glycoprotéine de spicule des coronavirus</term><term>Immunisation passive</term><term>Liaison aux protéines</term><term>Modèles animaux de maladie humaine</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Souris transgéniques</term><term>Syndrome respiratoire aigu sévère</term><term>Tests de neutralisation</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Anticorps monoclonal</term><term>Anticorps neutralisant</term><term>Homme</term><term>Immunoprophylaxie</term><term>Infection</term><term>Microbiologie</term><term>Souris</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract">Background. Severe acute respiratory syndrome (SARS) remains a significant public health concern after the epidemic in 2003. Human monoclonal antibodies (MAbs) that neutralize SARS-associated coronavirus (SARSCoV) could provide protection for exposed individuals. Methods. Transgenic mice with human immunoglobulin genes were immunized with the recombinant major surface (S) glycoprotein ectodomain of SARS-CoV. Epitopes of 2 neutralizing MAbs derived from these mice were mapped and evaluated in a murine model of SARS-CoV infection. Results. Both MAbs bound to S glycoprotein expressed on transfected cells but differed in their ability to block binding of S glycoprotein to Vero E6 cells. Immunoprecipitation analysis revealed 2 antibody-binding epitopes: one MAb (201) bound within the receptor-binding domain at aa 490–510, and the other MAb (68) bound externally to the domain at aa 130–150. Mice that received 40 mg/kg of either MAb prior to challenge with SARS-CoV were completely protected from virus replication in the lungs, and doses as low as 1.6 mg/kg offered significant protection. Conclusions. Two neutralizing epitopes were defined for MAbs to SARS-CoV S glycoprotein. Antibodies to both epitopes protected mice against SARS-CoV challenge. Clinical trials are planned to test MAb 201, a fully human MAb specific for the epitope within the receptor-binding region.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li><li>Massachusetts</li><li>New Jersey</li></region></list><tree><noCountry><name sortKey="Babcock, Gregory J" sort="Babcock, Gregory J" uniqKey="Babcock G" first="Gregory J." last="Babcock">Gregory J. Babcock</name><name sortKey="Coccia, Jennifer A" sort="Coccia, Jennifer A" uniqKey="Coccia J" first="Jennifer A." last="Coccia">Jennifer A. Coccia</name><name sortKey="Finberg, Robert W" sort="Finberg, Robert W" uniqKey="Finberg R" first="Robert W" last="Finberg">Robert W. Finberg</name><name sortKey="Greenough, Thomas C" sort="Greenough, Thomas C" uniqKey="Greenough T" first="Thomas C." last="Greenough">Thomas C. Greenough</name><name sortKey="Hernandez, Hector J" sort="Hernandez, Hector J" uniqKey="Hernandez H" first="Hector J." last="Hernandez">Hector J. Hernandez</name><name sortKey="Luzuriaga, Katherine" sort="Luzuriaga, Katherine" uniqKey="Luzuriaga K" first="Katherine" last="Luzuriaga">Katherine Luzuriaga</name><name sortKey="Somasundaran, Mohan" sort="Somasundaran, Mohan" uniqKey="Somasundaran M" first="Mohan" last="Somasundaran">Mohan Somasundaran</name><name sortKey="Sullivan, John L" sort="Sullivan, John L" uniqKey="Sullivan J" first="John L." last="Sullivan">John L. Sullivan</name><name sortKey="Thomas, William D" sort="Thomas, William D" uniqKey="Thomas W" first="William D." last="Thomas">William D. Thomas</name></noCountry><country name="États-Unis"><region name="Maryland"><name sortKey="Roberts, Anjeanette" sort="Roberts, Anjeanette" uniqKey="Roberts A" first="Anjeanette" last="Roberts">Anjeanette Roberts</name></region><name sortKey="Ambrosino, Donna M" sort="Ambrosino, Donna M" uniqKey="Ambrosino D" first="Donna M." last="Ambrosino">Donna M. Ambrosino</name><name sortKey="Ambrosino, Donna M" sort="Ambrosino, Donna M" uniqKey="Ambrosino D" first="Donna M." last="Ambrosino">Donna M. Ambrosino</name><name sortKey="Graziano, Robert F" sort="Graziano, Robert F" uniqKey="Graziano R" first="Robert F." last="Graziano">Robert F. Graziano</name><name sortKey="Lowy, Israel" sort="Lowy, Israel" uniqKey="Lowy I" first="Israel" last="Lowy">Israel Lowy</name><name sortKey="Srinivasan, Mohan" sort="Srinivasan, Mohan" uniqKey="Srinivasan M" first="Mohan" last="Srinivasan">Mohan Srinivasan</name><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name><name sortKey="Vogel, Leatrice" sort="Vogel, Leatrice" uniqKey="Vogel L" first="Leatrice" last="Vogel">Leatrice Vogel</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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