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Generation and characterization of human monoclonal neutralizing antibodies with distinct binding and sequence features against SARS coronavirus using XenoMouse®

Identifieur interne : 003E90 ( Main/Exploration ); précédent : 003E89; suivant : 003E91

Generation and characterization of human monoclonal neutralizing antibodies with distinct binding and sequence features against SARS coronavirus using XenoMouse®

Auteurs : Melissa Coughlin [États-Unis] ; Gin Lou [États-Unis] ; Osvaldo Martinez [États-Unis] ; Stephanie K. Masterman [Canada] ; Ole A. Olsen [Canada] ; Angelica A. Moksa [Canada] ; Michael Farzan [États-Unis] ; John S. Babcook [Canada] ; Bellur S. Prabhakar [États-Unis]

Source :

RBID : PMC:7103293

Descripteurs français

English descriptors

Abstract

Passive therapy with neutralizing human monoclonal antibodies (mAbs) could be an effective therapy against severe acute respiratory syndrome coronavirus (SARS-CoV). Utilizing the human immunoglobulin transgenic mouse, XenoMouse®, we produced fully human SARS-CoV spike (S) protein specific antibodies. Antibodies were examined for reactivity against a recombinant S1 protein, to which 200 antibodies reacted. Twenty-seven antibodies neutralized 200TCID50 SARS-CoV (Urbani). Additionally, 57 neutralizing antibodies were found that are likely specific to S2. Mapping of the binding region was achieved with several S1 recombinant proteins. Most S1 reactive neutralizing mAbs bound to the RBD, aa 318–510. However, two S1 specific mAbs reacted with a domain upstream of the RBD between aa 12 and 261. Immunoglobulin gene sequence analyses suggested at least 8 different binding specificities. Unique human mAbs could be used as a cocktail that would simultaneously target several neutralizing epitopes and prevent emergence of escape mutants.


Url:
DOI: 10.1016/j.virol.2006.09.029
PubMed: 17161858
PubMed Central: 7103293


Affiliations:


Links toward previous steps (curation, corpus...)


Le document en format XML

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<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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<term>Antibodies, Monoclonal (immunology)</term>
<term>Antibodies, Viral (biosynthesis)</term>
<term>Antibodies, Viral (genetics)</term>
<term>Antibodies, Viral (immunology)</term>
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<term>Alignement de séquences</term>
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<term>Anticorps antiviraux (génétique)</term>
<term>Anticorps antiviraux (immunologie)</term>
<term>Anticorps monoclonaux (biosynthèse)</term>
<term>Anticorps monoclonaux (génétique)</term>
<term>Anticorps monoclonaux (immunologie)</term>
<term>Données de séquences moléculaires</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires (immunologie)</term>
<term>Humains</term>
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<term>Antibodies, Monoclonal</term>
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<term>Anticorps antiviraux</term>
<term>Anticorps monoclonaux</term>
<term>Glycoprotéines membranaires</term>
<term>Hémagglutinines virales</term>
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<term>Hybridomas</term>
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<front>
<div type="abstract" xml:lang="en">
<p>Passive therapy with neutralizing human monoclonal antibodies (mAbs) could be an effective therapy against severe acute respiratory syndrome coronavirus (SARS-CoV). Utilizing the human immunoglobulin transgenic mouse, XenoMouse®, we produced fully human SARS-CoV spike (S) protein specific antibodies. Antibodies were examined for reactivity against a recombinant S1 protein, to which 200 antibodies reacted. Twenty-seven antibodies neutralized 200TCID
<sub>50</sub>
SARS-CoV (Urbani). Additionally, 57 neutralizing antibodies were found that are likely specific to S2. Mapping of the binding region was achieved with several S1 recombinant proteins. Most S1 reactive neutralizing mAbs bound to the RBD, aa 318–510. However, two S1 specific mAbs reacted with a domain upstream of the RBD between aa 12 and 261. Immunoglobulin gene sequence analyses suggested at least 8 different binding specificities. Unique human mAbs could be used as a cocktail that would simultaneously target several neutralizing epitopes and prevent emergence of escape mutants.</p>
</div>
</front>
<back>
<div1 type="bibliography">
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</affiliations>
</record>

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