Comprehensive profiling of neutralizing polyclonal sera targeting coxsackievirus B3

Abstract Despite their fundamental role in resolving viral infections, our understanding of how polyclonal neutralizing antibody responses target non-enveloped viruses remains limited. To define these responses, we obtained the full antigenic profile of multiple human and mouse polyclonal sera targe...

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Main Authors: Beatriz Álvarez-Rodríguez, Javier Buceta, Ron Geller
Format: Article
Language:English
Published: Nature Portfolio 2023-10-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-42144-2
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author Beatriz Álvarez-Rodríguez
Javier Buceta
Ron Geller
author_facet Beatriz Álvarez-Rodríguez
Javier Buceta
Ron Geller
author_sort Beatriz Álvarez-Rodríguez
collection DOAJ
description Abstract Despite their fundamental role in resolving viral infections, our understanding of how polyclonal neutralizing antibody responses target non-enveloped viruses remains limited. To define these responses, we obtained the full antigenic profile of multiple human and mouse polyclonal sera targeting the capsid of a prototypical picornavirus, coxsackievirus B3. Our results uncover significant variation in the breadth and strength of neutralization sites targeted by individual human polyclonal responses, which contrasted with homogenous responses observed in experimentally infected mice. We further use these comprehensive antigenic profiles to define key structural and evolutionary parameters that are predictive of escape, assess epitope dominance at the population level, and reveal a need for at least two mutations to achieve significant escape from multiple sera. Overall, our data provide a comprehensive analysis of how polyclonal sera target a non-enveloped viral capsid and help define both immune dominance and escape at the population level.
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spelling doaj.art-ba12145d1f9947409ff27bc3554480362023-11-20T10:02:28ZengNature PortfolioNature Communications2041-17232023-10-0114111610.1038/s41467-023-42144-2Comprehensive profiling of neutralizing polyclonal sera targeting coxsackievirus B3Beatriz Álvarez-Rodríguez0Javier Buceta1Ron Geller2Institute for Integrative Systems Biology (I2SysBio), Universitat de Valencia-CSICInstitute for Integrative Systems Biology (I2SysBio), Universitat de Valencia-CSICInstitute for Integrative Systems Biology (I2SysBio), Universitat de Valencia-CSICAbstract Despite their fundamental role in resolving viral infections, our understanding of how polyclonal neutralizing antibody responses target non-enveloped viruses remains limited. To define these responses, we obtained the full antigenic profile of multiple human and mouse polyclonal sera targeting the capsid of a prototypical picornavirus, coxsackievirus B3. Our results uncover significant variation in the breadth and strength of neutralization sites targeted by individual human polyclonal responses, which contrasted with homogenous responses observed in experimentally infected mice. We further use these comprehensive antigenic profiles to define key structural and evolutionary parameters that are predictive of escape, assess epitope dominance at the population level, and reveal a need for at least two mutations to achieve significant escape from multiple sera. Overall, our data provide a comprehensive analysis of how polyclonal sera target a non-enveloped viral capsid and help define both immune dominance and escape at the population level.https://doi.org/10.1038/s41467-023-42144-2
spellingShingle Beatriz Álvarez-Rodríguez
Javier Buceta
Ron Geller
Comprehensive profiling of neutralizing polyclonal sera targeting coxsackievirus B3
Nature Communications
title Comprehensive profiling of neutralizing polyclonal sera targeting coxsackievirus B3
title_full Comprehensive profiling of neutralizing polyclonal sera targeting coxsackievirus B3
title_fullStr Comprehensive profiling of neutralizing polyclonal sera targeting coxsackievirus B3
title_full_unstemmed Comprehensive profiling of neutralizing polyclonal sera targeting coxsackievirus B3
title_short Comprehensive profiling of neutralizing polyclonal sera targeting coxsackievirus B3
title_sort comprehensive profiling of neutralizing polyclonal sera targeting coxsackievirus b3
url https://doi.org/10.1038/s41467-023-42144-2
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