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Emergent variant modeling of the serological repertoire to norovirus in young children

Lindesmith, Lisa C; Brewer-Jensen, Paul D; Conrad, Helen; O'Reilly, Kathleen M; Mallory, Michael L; Kelly, Daniel; Williams, Rachel; ... Baric, Ralph S; + view all (2023) Emergent variant modeling of the serological repertoire to norovirus in young children. Cell Reports Medicine , 4 (3) , Article 100954. 10.1016/j.xcrm.2023.100954. Green open access

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Abstract

Human norovirus is the leading cause of acute gastroenteritis. Young children and the elderly bear the greatest burden of disease, representing more than 200,000 deaths annually. Infection prevalence peaks at younger than 2 years and is driven by novel GII.4 variants that emerge and spread globally. Using a surrogate neutralization assay, we characterize the evolution of the serological neutralizing antibody (nAb) landscape in young children as they transition between sequential GII.4 pandemic variants. Following upsurge of the replacement variant, antigenic cartography illustrates remodeling of the nAb landscape to the new variant accompanied by improved nAb titer. However, nAb relative avidity remains focused on the preceding variant. These data support immune imprinting as a mechanism of immune evasion and GII.4 virus persistence across a population. Understanding the complexities of immunity to rapidly evolving and co-circulating viral variants, like those of norovirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), and dengue viruses, will fundamentally inform vaccine design for emerging pathogens.

Type: Article
Title: Emergent variant modeling of the serological repertoire to norovirus in young children
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.xcrm.2023.100954
Publisher version: https://doi.org/10.1016/j.xcrm.2023.100954
Language: English
Additional information: © 2023 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: norovirus, neutralizing antibodies, blockade antibodies, antigenic cartography, variants of concern, antigenic seniority, immune imprinting
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
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 > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10167183
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