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.
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Sera from young children block binding of antigenically diverse GII.4 noroviruses
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GII.4 variant replacement shapes population serological antibody titer over time
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High-avidity antibody remains focused on previous, antigenically related GII.4 variants
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Immune imprinting molds GII.4 antibody responses and virus emergence potential
Norovirus GII.4 variants are a leading cause of gastroenteritis in children. Lindesmith et al. demonstrate that an emergent variant remodels antibody titer, while high-avidity antibody remains focused on the preceding related variant. These data support immune imprinting as a mechanism of GII.4 immune evasion and virus persistence.