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Development and Characterization of a Severe Acute Respiratory Syndrome—Associated Coronavirus—Neutralizing Human Monoclonal Antibody That Provides Effective Immunoprophylaxis in Mice

Identifieur interne : 000D35 ( Ncbi/Curation ); précédent : 000D34; suivant : 000D36

Development 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

Source :

RBID : PMC:7110081

Descripteurs français

English descriptors

Abstract

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:
DOI: 10.1086/427242
PubMed: 15655773
PubMed Central: 7110081

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PMC:7110081

Le document en format XML

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,
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<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>Immunization, Passive</term>
<term>Lung (virology)</term>
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<term>Mice, Inbred BALB C</term>
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<term>Protein Binding</term>
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<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>
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<term>Tests de neutralisation</term>
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<term>Épitopes</term>
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<term>Syndrome respiratoire aigu sévère</term>
<term>Tests de neutralisation</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<title>Abstract</title>
<p>
<bold>
<italic>Background.</italic>
</bold>
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.</p>
<p>
<bold>
<italic>Methods.</italic>
</bold>
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.</p>
<p>
<bold>
<italic>Results.</italic>
</bold>
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.</p>
<p>
<bold>
<italic>Conclusions.</italic>
</bold>
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.</p>
</div>
</front>
<back>
<div1 type="bibliography">
<listBibl>
<biblStruct>
<analytic>
<author>
<name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name>
</author>
<author>
<name sortKey="Gunther, S" uniqKey="Gunther S">S Gunther</name>
</author>
<author>
<name sortKey="Preiser, W" uniqKey="Preiser W">W Preiser</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Ksiazek, Tg" uniqKey="Ksiazek T">TG Ksiazek</name>
</author>
<author>
<name sortKey="Erdman, D" uniqKey="Erdman D">D Erdman</name>
</author>
<author>
<name sortKey="Goldsmith, Cs" uniqKey="Goldsmith C">CS Goldsmith</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Bisht, H" uniqKey="Bisht H">H Bisht</name>
</author>
<author>
<name sortKey="Roberts, A" uniqKey="Roberts A">A Roberts</name>
</author>
<author>
<name sortKey="Vogel, L" uniqKey="Vogel L">L Vogel</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Bukreyev, A" uniqKey="Bukreyev A">A Bukreyev</name>
</author>
<author>
<name sortKey="Lamirande, Ew" uniqKey="Lamirande E">EW Lamirande</name>
</author>
<author>
<name sortKey="Buchholz, Uj" uniqKey="Buchholz U">UJ Buchholz</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Yang, Zy" uniqKey="Yang Z">ZY Yang</name>
</author>
<author>
<name sortKey="Kong, Wp" uniqKey="Kong W">WP Kong</name>
</author>
<author>
<name sortKey="Huang, Y" uniqKey="Huang Y">Y Huang</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Sawyer, La" uniqKey="Sawyer L">LA Sawyer</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Popova, R" uniqKey="Popova R">R Popova</name>
</author>
<author>
<name sortKey="Zhang, X" uniqKey="Zhang X">X Zhang</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Bonavia, A" uniqKey="Bonavia A">A Bonavia</name>
</author>
<author>
<name sortKey="Zelus, Bd" uniqKey="Zelus B">BD Zelus</name>
</author>
<author>
<name sortKey="Wentworth, De" uniqKey="Wentworth D">DE Wentworth</name>
</author>
<author>
<name sortKey="Talbot, Pj" uniqKey="Talbot P">PJ Talbot</name>
</author>
<author>
<name sortKey="Holmes, Kv" uniqKey="Holmes K">KV Holmes</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Kuo, L" uniqKey="Kuo L">L Kuo</name>
</author>
<author>
<name sortKey="Godeke, Gj" uniqKey="Godeke G">GJ Godeke</name>
</author>
<author>
<name sortKey="Raamsman, Mj" uniqKey="Raamsman M">MJ Raamsman</name>
</author>
<author>
<name sortKey="Masters, Ps" uniqKey="Masters P">PS Masters</name>
</author>
<author>
<name sortKey="Rottier, Pj" uniqKey="Rottier P">PJ Rottier</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Gallagher, Tm" uniqKey="Gallagher T">TM Gallagher</name>
</author>
<author>
<name sortKey="Buchmeier, Mj" uniqKey="Buchmeier M">MJ Buchmeier</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Li, W" uniqKey="Li W">W Li</name>
</author>
<author>
<name sortKey="Moore, Mj" uniqKey="Moore M">MJ Moore</name>
</author>
<author>
<name sortKey="Vasilieva, N" uniqKey="Vasilieva N">N Vasilieva</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Babcock, Gj" uniqKey="Babcock G">GJ Babcock</name>
</author>
<author>
<name sortKey="Esshaki, Dj" uniqKey="Esshaki D">DJ Esshaki</name>
</author>
<author>
<name sortKey="Thomas, Wd" uniqKey="Thomas W">WD Thomas</name>
</author>
<author>
<name sortKey="Ambrosino, Dm" uniqKey="Ambrosino D">DM Ambrosino</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Wong, Sk" uniqKey="Wong S">SK Wong</name>
</author>
<author>
<name sortKey="Li, W" uniqKey="Li W">W Li</name>
</author>
<author>
<name sortKey="Moore, Mj" uniqKey="Moore M">MJ Moore</name>
</author>
<author>
<name sortKey="Choe, H" uniqKey="Choe H">H Choe</name>
</author>
<author>
<name sortKey="Farzan, M" uniqKey="Farzan M">M Farzan</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Witte, Kh" uniqKey="Witte K">KH Witte</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Reed, Lv" uniqKey="Reed L">LV Reed</name>
</author>
<author>
<name sortKey="Muench, H" uniqKey="Muench H">H Muench</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Subbarao, K" uniqKey="Subbarao K">K Subbarao</name>
</author>
<author>
<name sortKey="Mcauliffe, J" uniqKey="Mcauliffe J">J McAuliffe</name>
</author>
<author>
<name sortKey="Vogel, L" uniqKey="Vogel L">L Vogel</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Rich, Rl" uniqKey="Rich R">RL Rich</name>
</author>
<author>
<name sortKey="Myszka, Dg" uniqKey="Myszka D">DG Myszka</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Johnson, S" uniqKey="Johnson S">S Johnson</name>
</author>
<author>
<name sortKey="Griego, Sd" uniqKey="Griego S">SD Griego</name>
</author>
<author>
<name sortKey="Pfarr, Ds" uniqKey="Pfarr D">DS Pfarr</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Meissner, Hc" uniqKey="Meissner H">HC Meissner</name>
</author>
<author>
<name sortKey="Long, Ss" uniqKey="Long S">SS Long</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Sui, J" uniqKey="Sui J">J Sui</name>
</author>
<author>
<name sortKey="Li, W" uniqKey="Li W">W Li</name>
</author>
<author>
<name sortKey="Murakami, A" uniqKey="Murakami A">A Murakami</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Yeh, Sh" uniqKey="Yeh S">SH Yeh</name>
</author>
<author>
<name sortKey="Wang, Hy" uniqKey="Wang H">HY Wang</name>
</author>
<author>
<name sortKey="Tsai, Cy" uniqKey="Tsai C">CY Tsai</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Guan, Y" uniqKey="Guan Y">Y Guan</name>
</author>
<author>
<name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name>
</author>
<author>
<name sortKey="Zheng, B" uniqKey="Zheng B">B Zheng</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
</listBibl>
</div1>
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