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The Human Immune Response to Dengue Virus Is Dominated by Highly Cross-Reactive Antibodies Endowed with Neutralizing and Enhancing Activity

Identifieur interne : 006E71 ( Main/Exploration ); précédent : 006E70; suivant : 006E72

The Human Immune Response to Dengue Virus Is Dominated by Highly Cross-Reactive Antibodies Endowed with Neutralizing and Enhancing Activity

Auteurs : Martina Beltramello [Suisse] ; Katherine L. Williams [États-Unis] ; Cameron P. Simmons ; Annalisa Macagno [Suisse] ; Luca Simonelli [Suisse] ; Nguyen Than Ha Quyen ; Soila Sukupolvi-Petty [États-Unis] ; Erika Navarro-Sanchez [France] ; Paul R. Young [Australie] ; Aravinda M. De Silva [États-Unis] ; Félix A. Rey [France] ; Luca Varani [Suisse] ; Stephen S. Whitehead [États-Unis] ; Michael S. Diamond [États-Unis] ; Eva Harris [États-Unis] ; Antonio Lanzavecchia [Suisse] ; Federica Sallusto [Suisse]

Source :

RBID : PMC:3884547

Abstract

Summary

Antibodies protect against homologous Dengue virus (DENV) infection but can precipitate severe dengue by promoting heterotypic virus entry via Fcγ receptors (FcγR). We immortalized memory B cells from individuals after primary or secondary infection and analyzed anti-DENV monoclonal antibodies (mAbs) thus generated. MAbs to envelope (E) protein domain III (DIII) were either serotype specific or cross-reactive and potently neutralized DENV infection. DI/DII- or viral membrane protein prM-reactive mAbs neutralized poorly and showed broad cross-reactivity with the four DENV serotypes. All mAbs enhanced infection at subneutralizing concentrations. Three mAbs targeting distinct epitopes on the four DENV serotypes and engineered to prevent FcγR binding did not enhance infection and neutralized DENV in vitro and in vivo as postexposure therapy in a mouse model of lethal DENV infection. Our findings reveal an unexpected degree of cross-reactivity in human antibodies against DENV and illustrate the potential for an antibody-based therapy to control severe dengue.


Url:
DOI: 10.1016/j.chom.2010.08.007
PubMed: 20833378
PubMed Central: 3884547


Affiliations:


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Le document en format XML

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<name sortKey="Beltramello, Martina" sort="Beltramello, Martina" uniqKey="Beltramello M" first="Martina" last="Beltramello">Martina Beltramello</name>
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<name sortKey="De Silva, Aravinda M" sort="De Silva, Aravinda M" uniqKey="De Silva A" first="Aravinda M." last="De Silva">Aravinda M. De Silva</name>
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<wicri:regionArea>Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599</wicri:regionArea>
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<region type="state">Caroline du Nord</region>
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<name sortKey="Varani, Luca" sort="Varani, Luca" uniqKey="Varani L" first="Luca" last="Varani">Luca Varani</name>
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<nlm:aff id="A1">Institute for Research in Biomedicine, Bellinzona, 6500, Switzerland</nlm:aff>
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<name sortKey="Whitehead, Stephen S" sort="Whitehead, Stephen S" uniqKey="Whitehead S" first="Stephen S." last="Whitehead">Stephen S. Whitehead</name>
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<name sortKey="Diamond, Michael S" sort="Diamond, Michael S" uniqKey="Diamond M" first="Michael S." last="Diamond">Michael S. Diamond</name>
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<name sortKey="Harris, Eva" sort="Harris, Eva" uniqKey="Harris E" first="Eva" last="Harris">Eva Harris</name>
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<nlm:aff id="A2">Division of Infectious Diseases, University of California, Berkeley, CA 94720-7354, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<region type="state">Californie</region>
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<name sortKey="Lanzavecchia, Antonio" sort="Lanzavecchia, Antonio" uniqKey="Lanzavecchia A" first="Antonio" last="Lanzavecchia">Antonio Lanzavecchia</name>
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<nlm:aff id="A1">Institute for Research in Biomedicine, Bellinzona, 6500, Switzerland</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Institute for Research in Biomedicine, Bellinzona, 6500</wicri:regionArea>
<wicri:noRegion>6500</wicri:noRegion>
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<name sortKey="Sallusto, Federica" sort="Sallusto, Federica" uniqKey="Sallusto F" first="Federica" last="Sallusto">Federica Sallusto</name>
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<nlm:aff id="A1">Institute for Research in Biomedicine, Bellinzona, 6500, Switzerland</nlm:aff>
<country xml:lang="fr">Suisse</country>
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<title level="j">Cell host & microbe</title>
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<div type="abstract" xml:lang="en">
<title>Summary</title>
<p id="P1">Antibodies protect against homologous Dengue virus (DENV) infection but can precipitate severe dengue by promoting heterotypic virus entry via Fcγ receptors (FcγR). We immortalized memory B cells from individuals after primary or secondary infection and analyzed anti-DENV monoclonal antibodies (mAbs) thus generated. MAbs to envelope (E) protein domain III (DIII) were either serotype specific or cross-reactive and potently neutralized DENV infection. DI/DII- or viral membrane protein prM-reactive mAbs neutralized poorly and showed broad cross-reactivity with the four DENV serotypes. All mAbs enhanced infection at subneutralizing concentrations. Three mAbs targeting distinct epitopes on the four DENV serotypes and engineered to prevent FcγR binding did not enhance infection and neutralized DENV
<italic>in vitro</italic>
and
<italic>in vivo</italic>
as postexposure therapy in a mouse model of lethal DENV infection. Our findings reveal an unexpected degree of cross-reactivity in human antibodies against DENV and illustrate the potential for an antibody-based therapy to control severe dengue.</p>
</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Australie</li>
<li>France</li>
<li>Suisse</li>
<li>États-Unis</li>
</country>
<region>
<li>Californie</li>
<li>Caroline du Nord</li>
<li>Maryland</li>
<li>Missouri (État)</li>
<li>Île-de-France</li>
</region>
<settlement>
<li>Saint-Louis (Missouri)</li>
</settlement>
<orgName>
<li>École de médecine (Université Washington de Saint-Louis)</li>
</orgName>
</list>
<tree>
<noCountry>
<name sortKey="Quyen, Nguyen Than Ha" sort="Quyen, Nguyen Than Ha" uniqKey="Quyen N" first="Nguyen Than Ha" last="Quyen">Nguyen Than Ha Quyen</name>
<name sortKey="Simmons, Cameron P" sort="Simmons, Cameron P" uniqKey="Simmons C" first="Cameron P." last="Simmons">Cameron P. Simmons</name>
</noCountry>
<country name="Suisse">
<noRegion>
<name sortKey="Beltramello, Martina" sort="Beltramello, Martina" uniqKey="Beltramello M" first="Martina" last="Beltramello">Martina Beltramello</name>
</noRegion>
<name sortKey="Lanzavecchia, Antonio" sort="Lanzavecchia, Antonio" uniqKey="Lanzavecchia A" first="Antonio" last="Lanzavecchia">Antonio Lanzavecchia</name>
<name sortKey="Macagno, Annalisa" sort="Macagno, Annalisa" uniqKey="Macagno A" first="Annalisa" last="Macagno">Annalisa Macagno</name>
<name sortKey="Sallusto, Federica" sort="Sallusto, Federica" uniqKey="Sallusto F" first="Federica" last="Sallusto">Federica Sallusto</name>
<name sortKey="Simonelli, Luca" sort="Simonelli, Luca" uniqKey="Simonelli L" first="Luca" last="Simonelli">Luca Simonelli</name>
<name sortKey="Varani, Luca" sort="Varani, Luca" uniqKey="Varani L" first="Luca" last="Varani">Luca Varani</name>
</country>
<country name="États-Unis">
<region name="Californie">
<name sortKey="Williams, Katherine L" sort="Williams, Katherine L" uniqKey="Williams K" first="Katherine L." last="Williams">Katherine L. Williams</name>
</region>
<name sortKey="De Silva, Aravinda M" sort="De Silva, Aravinda M" uniqKey="De Silva A" first="Aravinda M." last="De Silva">Aravinda M. De Silva</name>
<name sortKey="Diamond, Michael S" sort="Diamond, Michael S" uniqKey="Diamond M" first="Michael S." last="Diamond">Michael S. Diamond</name>
<name sortKey="Harris, Eva" sort="Harris, Eva" uniqKey="Harris E" first="Eva" last="Harris">Eva Harris</name>
<name sortKey="Sukupolvi Petty, Soila" sort="Sukupolvi Petty, Soila" uniqKey="Sukupolvi Petty S" first="Soila" last="Sukupolvi-Petty">Soila Sukupolvi-Petty</name>
<name sortKey="Whitehead, Stephen S" sort="Whitehead, Stephen S" uniqKey="Whitehead S" first="Stephen S." last="Whitehead">Stephen S. Whitehead</name>
</country>
<country name="France">
<noRegion>
<name sortKey="Navarro Sanchez, Erika" sort="Navarro Sanchez, Erika" uniqKey="Navarro Sanchez E" first="Erika" last="Navarro-Sanchez">Erika Navarro-Sanchez</name>
</noRegion>
<name sortKey="Rey, Felix A" sort="Rey, Felix A" uniqKey="Rey F" first="Félix A." last="Rey">Félix A. Rey</name>
</country>
<country name="Australie">
<noRegion>
<name sortKey="Young, Paul R" sort="Young, Paul R" uniqKey="Young P" first="Paul R." last="Young">Paul R. Young</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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