Antigenic Site Immunodominance Redirection Following Repeat Variant Exposure

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2022 Jun 24

PMID 35746763

Authors

Lisa C Lindesmith

Paul D Brewer-Jensen

Michael L Mallory

Mark R Zweigart

Samantha R May

Daniel Kelly

Rachel Williams

Sylvia Becker-Dreps

Filemon Bucardo

David J Allen

Judith Breuer

Ralph S Baric

Affiliations

Soon will be listed here.

Abstract

Human norovirus is a leading cause of acute gastroenteritis, driven by antigenic variants within the GII.4 genotype. Antibody responses to GII.4 vaccination in adults are shaped by immune memory. How children without extensive immune memory will respond to GII.4 vaccination has not been reported. Here, we characterized the GII.4 neutralizing antibody (nAb) landscape following natural infection using a surrogate assay and antigenic site chimera virus-like particles. We demonstrate that the nAb landscape changes with age and virus exposure. Among sites A, C, and G, nAbs from first infections are focused on sites A and C. As immunity develops with age/exposure, site A is supplemented with antibodies that bridge site A to sites C and G. Cross-site nAbs continue to develop into adulthood, accompanied by an increase in nAb to site G. Continued exposure to GII.4 2012 Sydney correlated with a shift to co-dominance of sites A and G. Furthermore, site G nAbs correlated with the broadening of nAb titer across antigenically divergent variants. These data describe fundamental steps in the development of immunity to GII.4 over a lifetime, and illustrate how the antigenicity of one pandemic variant could influence the pandemic potential of another variant through the redirection of immunodominant epitopes.

Citing Articles

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