Comprehensive profiling of neutralizing polyclonal sera targeting coxsackievirus B3

Beatriz Álvarez-Rodríguez (), Javier Buceta () and Ron Geller ()
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Beatriz Álvarez-Rodríguez: Universitat de Valencia-CSIC
Javier Buceta: Universitat de Valencia-CSIC
Ron Geller: Universitat de Valencia-CSIC

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-42144-2

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