SrasV1, Main, Merge, bibRecord, 005192

Development and characterization of a severe acute respiratory syndrome-associated coronairus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice

Identifieur interne : 005192 ( Main/Merge ); précédent : 005191; suivant : 005193

Development and characterization of a severe acute respiratory syndrome-associated coronairus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice

Auteurs : Thomas C. Greenough [États-Unis] ; Gregory J. Babcock [États-Unis] ; Anjeanette Roberts [États-Unis] ; Hector J. Hernandez [États-Unis] ; William D. Jr Thomas [États-Unis] ; Jennifer A. Coccia [États-Unis] ; Robert F. Graziano [États-Unis] ; Mohan Srinivasan [États-Unis] ; Israel Lowy [États-Unis] ; Robert W. Finberg [États-Unis] ; Kanta Subbarao [États-Unis] ; Leatrice Vogel [États-Unis] ; Mohan Somasundaran [États-Unis] ; Katherine Luzuriaga [États-Unis] ; John L. Sullivan [États-Unis] ; Donna M. Ambrosino [États-Unis]

Source :

The Journal of infectious diseases [ 0022-1899 ] ; 2005.

RBID : Pascal:05-0173830

Descripteurs français

Pascal (Inist)
- Homme, Souris, Anticorps neutralisant, Anticorps monoclonal, Immunoprophylaxie, Microbiologie, Infection, Syndrome respiratoire aigu sévère.
Wicri :
- topic : Homme.

English descriptors

KwdEn :
- Human, Immunoprophylaxis, Infection, Microbiology, Monoclonal antibody, Mouse, Neutralizing antibody, Severe acute respiratory syndrome.

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 (SARS-CoV) 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.

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Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Development and characterization of a severe acute respiratory syndrome-associated coronairus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice</title>
<author><name sortKey="Greenough, Thomas C" sort="Greenough, Thomas C" uniqKey="Greenough T" first="Thomas C." last="Greenough">Thomas C. Greenough</name>
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<s2>Bethesda, Maryland</s2>
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<author><name sortKey="Somasundaran, Mohan" sort="Somasundaran, Mohan" uniqKey="Somasundaran M" first="Mohan" last="Somasundaran">Mohan Somasundaran</name>
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</author>
<author><name sortKey="Luzuriaga, Katherine" sort="Luzuriaga, Katherine" uniqKey="Luzuriaga K" first="Katherine" last="Luzuriaga">Katherine Luzuriaga</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Departments of Pediatrics and Medicine, Program in Molecular Medicine, University of Massachusetts Medical School</s1>
<s2>Worcester</s2>
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</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:level="1"><inist:fA14 i1="01"><s1>Departments of Pediatrics and Medicine, Program in Molecular Medicine, University of Massachusetts Medical School</s1>
<s2>Worcester</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Worcester</wicri:noRegion>
</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 wicri:level="1"><inist:fA14 i1="02"><s1>Massachusetts Biologic Laboratories, University of Massachusetts Medical School</s1>
<s2>Jamaica Plain</s2>
<s3>USA</s3>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Jamaica Plain</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">The Journal of infectious diseases</title>
<title level="j" type="abbreviated">J. infect. dis.</title>
<idno type="ISSN">0022-1899</idno>
<imprint><date when="2005">2005</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">The Journal of infectious diseases</title>
<title level="j" type="abbreviated">J. infect. dis.</title>
<idno type="ISSN">0022-1899</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Human</term>
<term>Immunoprophylaxis</term>
<term>Infection</term>
<term>Microbiology</term>
<term>Monoclonal antibody</term>
<term>Mouse</term>
<term>Neutralizing antibody</term>
<term>Severe acute respiratory syndrome</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Homme</term>
<term>Souris</term>
<term>Anticorps neutralisant</term>
<term>Anticorps monoclonal</term>
<term>Immunoprophylaxie</term>
<term>Microbiologie</term>
<term>Infection</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" xml:lang="en">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 (SARS-CoV) 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>New Jersey</li>
</region>
</list>
<tree><country name="États-Unis"><noRegion><name sortKey="Greenough, Thomas C" sort="Greenough, Thomas C" uniqKey="Greenough T" first="Thomas C." last="Greenough">Thomas C. Greenough</name>
</noRegion>
<name sortKey="Ambrosino, Donna M" sort="Ambrosino, Donna M" uniqKey="Ambrosino D" first="Donna M." last="Ambrosino">Donna M. Ambrosino</name>
<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="Graziano, Robert F" sort="Graziano, Robert F" uniqKey="Graziano R" first="Robert F." last="Graziano">Robert F. Graziano</name>
<name sortKey="Hernandez, Hector J" sort="Hernandez, Hector J" uniqKey="Hernandez H" first="Hector J." last="Hernandez">Hector J. Hernandez</name>
<name sortKey="Lowy, Israel" sort="Lowy, Israel" uniqKey="Lowy I" first="Israel" last="Lowy">Israel Lowy</name>
<name sortKey="Luzuriaga, Katherine" sort="Luzuriaga, Katherine" uniqKey="Luzuriaga K" first="Katherine" last="Luzuriaga">Katherine Luzuriaga</name>
<name sortKey="Roberts, Anjeanette" sort="Roberts, Anjeanette" uniqKey="Roberts A" first="Anjeanette" last="Roberts">Anjeanette Roberts</name>
<name sortKey="Somasundaran, Mohan" sort="Somasundaran, Mohan" uniqKey="Somasundaran M" first="Mohan" last="Somasundaran">Mohan Somasundaran</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="Sullivan, John L" sort="Sullivan, John L" uniqKey="Sullivan J" first="John L." last="Sullivan">John L. Sullivan</name>
<name sortKey="Thomas, William D Jr" sort="Thomas, William D Jr" uniqKey="Thomas W" first="William D. Jr" last="Thomas">William D. Jr Thomas</name>
<name sortKey="Vogel, Leatrice" sort="Vogel, Leatrice" uniqKey="Vogel L" first="Leatrice" last="Vogel">Leatrice Vogel</name>
</country>
</tree>
</affiliations>
</record>

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Development and characterization of a severe acute respiratory syndrome-associated coronairus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice

Development and characterization of a severe acute respiratory syndrome-associated coronairus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice

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