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On a mouse monoclonal antibody that neutralizes all four dengue virus serotypes

Identifieur interne : 002963 ( PascalFrancis/Checkpoint ); précédent : 002962; suivant : 002964

On a mouse monoclonal antibody that neutralizes all four dengue virus serotypes

Auteurs : Ravikumar Rajamanonmani [Singapour] ; Celine Nkenfou [Singapour] ; Paula Clancy [Australie] ; YIN HOE YAU [Singapour] ; Susana Geifman Shochat [Singapour] ; Soila Sukupolvi-Petty [États-Unis] ; Wouter Schul [Singapour] ; Michael S. Diamond [États-Unis] ; Subhash G. Vasudevan [Singapour, Australie] ; Julien Lescar [Singapour, France]

Source :

RBID : Pascal:09-0162365

Descripteurs français

English descriptors

Abstract

The flavivirus envelope glycoprotein (E) is responsible for viral attachment and entry by membrane fusion. Its ectodomain is the primary target of the humoral immune response. In particular, the C-terminal Ig-like domain III of E, which is exposed at the surface of the viral particle, forms an attractive antigen for raising protective monoclonal antibodies (mAb). 9F12, a mouse mAb raised against a dengue virus (DENV) serotype 2 recombinant domain III, cross-reacts with corresponding domains from the other three DENV serotypes and also with West Nile virus. mAb 9F1 2 binds with nanomolar affinity to a conserved epitope that maps to the viral surface comprising residues 305, 307, 310 and 330 of the E protein. mAb 9F1 2 neutralizes all four DENV serotypes in plaque reduction assays. We expressed a single-chain Fv from 9F12 that retains the binding activity of the parent mAb. Adsorption and fusion inhibition assays indicate that mAb 9F1 2 prevents early steps of viral entry. Its virus inhibition activity and broad cross-reactivity makes mAb 9F12 a suitable candidate for optimization and humanization into a therapeutic antibody to treat severe infections by dengue.


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Pascal:09-0162365

Le document en format XML

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<div type="abstract" xml:lang="en">The flavivirus envelope glycoprotein (E) is responsible for viral attachment and entry by membrane fusion. Its ectodomain is the primary target of the humoral immune response. In particular, the C-terminal Ig-like domain III of E, which is exposed at the surface of the viral particle, forms an attractive antigen for raising protective monoclonal antibodies (mAb). 9F12, a mouse mAb raised against a dengue virus (DENV) serotype 2 recombinant domain III, cross-reacts with corresponding domains from the other three DENV serotypes and also with West Nile virus. mAb 9F1 2 binds with nanomolar affinity to a conserved epitope that maps to the viral surface comprising residues 305, 307, 310 and 330 of the E protein. mAb 9F1 2 neutralizes all four DENV serotypes in plaque reduction assays. We expressed a single-chain Fv from 9F12 that retains the binding activity of the parent mAb. Adsorption and fusion inhibition assays indicate that mAb 9F1 2 prevents early steps of viral entry. Its virus inhibition activity and broad cross-reactivity makes mAb 9F12 a suitable candidate for optimization and humanization into a therapeutic antibody to treat severe infections by dengue.</div>
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<sZ>7 aut.</sZ>
</fA14>
<fA14 i1="04">
<s1>Department of Biochemistry and Molecular Biology, James Cook University</s1>
<s3>AUS</s3>
<sZ>3 aut.</sZ>
<sZ>9 aut.</sZ>
</fA14>
<fA14 i1="05">
<s1>Departments of Medicine, Molecular Microbiology, Pathology and Immunology, Washington University School of Medicine</s1>
<s2>St Louis</s2>
<s3>USA</s3>
<sZ>6 aut.</sZ>
<sZ>8 aut.</sZ>
</fA14>
<fA14 i1="06">
<s1>AFMB CNRS UMR6098</s1>
<s2>Marseille</s2>
<s3>FRA</s3>
<sZ>10 aut.</sZ>
</fA14>
<fA20>
<s1>799-809</s1>
</fA20>
<fA21>
<s1>2009</s1>
</fA21>
<fA23 i1="01">
<s0>ENG</s0>
</fA23>
<fA43 i1="01">
<s1>INIST</s1>
<s2>13533</s2>
<s5>354000187410180030</s5>
</fA43>
<fA44>
<s0>0000</s0>
<s1>© 2009 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45>
<s0>1 p.3/4</s0>
</fA45>
<fA47 i1="01" i2="1">
<s0>09-0162365</s0>
</fA47>
<fA60>
<s1>P</s1>
</fA60>
<fA61>
<s0>A</s0>
</fA61>
<fA64 i1="01" i2="1">
<s0>Journal of general virology</s0>
</fA64>
<fA66 i1="01">
<s0>GBR</s0>
</fA66>
<fC01 i1="01" l="ENG">
<s0>The flavivirus envelope glycoprotein (E) is responsible for viral attachment and entry by membrane fusion. Its ectodomain is the primary target of the humoral immune response. In particular, the C-terminal Ig-like domain III of E, which is exposed at the surface of the viral particle, forms an attractive antigen for raising protective monoclonal antibodies (mAb). 9F12, a mouse mAb raised against a dengue virus (DENV) serotype 2 recombinant domain III, cross-reacts with corresponding domains from the other three DENV serotypes and also with West Nile virus. mAb 9F1 2 binds with nanomolar affinity to a conserved epitope that maps to the viral surface comprising residues 305, 307, 310 and 330 of the E protein. mAb 9F1 2 neutralizes all four DENV serotypes in plaque reduction assays. We expressed a single-chain Fv from 9F12 that retains the binding activity of the parent mAb. Adsorption and fusion inhibition assays indicate that mAb 9F1 2 prevents early steps of viral entry. Its virus inhibition activity and broad cross-reactivity makes mAb 9F12 a suitable candidate for optimization and humanization into a therapeutic antibody to treat severe infections by dengue.</s0>
</fC01>
<fC02 i1="01" i2="X">
<s0>002A05C10</s0>
</fC02>
<fC02 i1="02" i2="X">
<s0>002A05C07</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE">
<s0>Souris</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG">
<s0>Mouse</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA">
<s0>Ratón</s0>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE">
<s0>Virus dengue</s0>
<s2>NW</s2>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG">
<s0>Dengue virus</s0>
<s2>NW</s2>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA">
<s0>Dengue virus</s0>
<s2>NW</s2>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE">
<s0>Animal</s0>
<s5>05</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG">
<s0>Animal</s0>
<s5>05</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA">
<s0>Animal</s0>
<s5>05</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE">
<s0>Anticorps monoclonal</s0>
<s5>06</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG">
<s0>Monoclonal antibody</s0>
<s5>06</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA">
<s0>Anticuerpo monoclonal</s0>
<s5>06</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE">
<s0>Sérotype</s0>
<s5>07</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG">
<s0>Serotype</s0>
<s5>07</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA">
<s0>Serotipo</s0>
<s5>07</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE">
<s0>Microbiologie</s0>
<s5>08</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG">
<s0>Microbiology</s0>
<s5>08</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA">
<s0>Microbiología</s0>
<s5>08</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE">
<s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG">
<s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA">
<s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE">
<s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="02" i2="X" l="ENG">
<s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="02" i2="X" l="SPA">
<s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="03" i2="X" l="FRE">
<s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG">
<s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA">
<s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="04" i2="X" l="FRE">
<s0>Virus groupe dengue</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="ENG">
<s0>Dengue group virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="SPA">
<s0>Dengue group virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="FRE">
<s0>Flavivirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="ENG">
<s0>Flavivirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="SPA">
<s0>Flavivirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="06" i2="X" l="FRE">
<s0>Flaviviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="06" i2="X" l="ENG">
<s0>Flaviviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="06" i2="X" l="SPA">
<s0>Flaviviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="07" i2="X" l="FRE">
<s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="07" i2="X" l="ENG">
<s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="07" i2="X" l="SPA">
<s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fN21>
<s1>117</s1>
</fN21>
<fN44 i1="01">
<s1>OTO</s1>
</fN44>
<fN82>
<s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
<affiliations>
<list>
<country>
<li>Australie</li>
<li>France</li>
<li>Singapour</li>
<li>États-Unis</li>
</country>
<region>
<li>Missouri (État)</li>
<li>Provence-Alpes-Côte d'Azur</li>
</region>
<settlement>
<li>Marseille</li>
<li>Saint-Louis (Missouri)</li>
</settlement>
<orgName>
<li>Université Washington de Saint-Louis</li>
<li>École de médecine (Université Washington de Saint-Louis)</li>
</orgName>
</list>
<tree>
<country name="Singapour">
<noRegion>
<name sortKey="Rajamanonmani, Ravikumar" sort="Rajamanonmani, Ravikumar" uniqKey="Rajamanonmani R" first="Ravikumar" last="Rajamanonmani">Ravikumar Rajamanonmani</name>
</noRegion>
<name sortKey="Geifman Shochat, Susana" sort="Geifman Shochat, Susana" uniqKey="Geifman Shochat S" first="Susana" last="Geifman Shochat">Susana Geifman Shochat</name>
<name sortKey="Lescar, Julien" sort="Lescar, Julien" uniqKey="Lescar J" first="Julien" last="Lescar">Julien Lescar</name>
<name sortKey="Nkenfou, Celine" sort="Nkenfou, Celine" uniqKey="Nkenfou C" first="Celine" last="Nkenfou">Celine Nkenfou</name>
<name sortKey="Rajamanonmani, Ravikumar" sort="Rajamanonmani, Ravikumar" uniqKey="Rajamanonmani R" first="Ravikumar" last="Rajamanonmani">Ravikumar Rajamanonmani</name>
<name sortKey="Schul, Wouter" sort="Schul, Wouter" uniqKey="Schul W" first="Wouter" last="Schul">Wouter Schul</name>
<name sortKey="Vasudevan, Subhash G" sort="Vasudevan, Subhash G" uniqKey="Vasudevan S" first="Subhash G." last="Vasudevan">Subhash G. Vasudevan</name>
<name sortKey="Yin Hoe Yau" sort="Yin Hoe Yau" uniqKey="Yin Hoe Yau" last="Yin Hoe Yau">YIN HOE YAU</name>
</country>
<country name="Australie">
<noRegion>
<name sortKey="Clancy, Paula" sort="Clancy, Paula" uniqKey="Clancy P" first="Paula" last="Clancy">Paula Clancy</name>
</noRegion>
<name sortKey="Vasudevan, Subhash G" sort="Vasudevan, Subhash G" uniqKey="Vasudevan S" first="Subhash G." last="Vasudevan">Subhash G. Vasudevan</name>
</country>
<country name="États-Unis">
<region name="Missouri (État)">
<name sortKey="Sukupolvi Petty, Soila" sort="Sukupolvi Petty, Soila" uniqKey="Sukupolvi Petty S" first="Soila" last="Sukupolvi-Petty">Soila Sukupolvi-Petty</name>
</region>
<name sortKey="Diamond, Michael S" sort="Diamond, Michael S" uniqKey="Diamond M" first="Michael S." last="Diamond">Michael S. Diamond</name>
</country>
<country name="France">
<region name="Provence-Alpes-Côte d'Azur">
<name sortKey="Lescar, Julien" sort="Lescar, Julien" uniqKey="Lescar J" first="Julien" last="Lescar">Julien Lescar</name>
</region>
</country>
</tree>
</affiliations>
</record>

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