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Antigenic Site Immunodominance Redirection Following Repeat Variant Exposure

Lindesmith, Lisa C; Brewer-Jensen, Paul D; Mallory, Michael L; Zweigart, Mark R; May, Samantha R; Kelly, Daniel; Williams, Rachel; ... Baric, Ralph S; + view all (2022) Antigenic Site Immunodominance Redirection Following Repeat Variant Exposure. Viruses , 14 (6) , Article 1293. 10.3390/v14061293. Green open access

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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.

Type: Article
Title: Antigenic Site Immunodominance Redirection Following Repeat Variant Exposure
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/v14061293
Publisher version: https://doi.org/10.3390/v14061293
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Science & Technology, Life Sciences & Biomedicine, Virology, norovirus, neutralizing antibody, blockade antibody, immunodominance, variants of concern, antigenic seniority, immune imprinting, variant persistence, BIRTH COHORT, NOROVIRUS, GASTROENTERITIS, CHILDREN, EPIDEMIOLOGY, REPLICATION, EMERGENCE, RESPONSES, GENOTYPES, DISEASE
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10151887
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