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

Lindesmith, Lisa C.; Brewer-Jensen, Paul D.; Conrad, Helen; O’Reilly, Kathleen; Mallory, Michael L.; Kelly, Daniel; Williams, Rachel; Edmunds, W. John; Allen, David J.; Breuer, Judith; Baric, Ralph S.

doi:10.1016/j.xcrm.2023.100954

Cited by 3 publications

(1 citation statement)

References 97 publications

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“…Our models extend catalytic models to enable the incorporation of the birth cohort’s lifetime DENV exposures, allowing for serotype-specific inferences and the specific antigenic relationship of the viruses causing sequential infections. Our approach to bring together sequence data, antigenic maps, and surveillance data into integrative frameworks will be relevant to other antigenically variable pathogens, including influenza virus, SARS-CoV-2, and norovirus ( 1 , 2 , 28 ). They also provide a route to determining the evolutionary pathways that viruses may take in adapting to local immunity.…”

Section: Discussionmentioning

confidence: 99%

Antigenic distance between primary and secondary dengue infections correlates with disease risk

Wang,

Huang,

Katzelnick

et al. 2024

Sci. Transl. Med.

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Many pathogens continuously change their protein structure in response to immune-driven selection, resulting in weakened protection even in previously exposed individuals. In addition, for some pathogens, such as dengue virus, poorly targeted immunity is associated with increased risk of severe disease through a mechanism known as antibody-dependent enhancement. However, it remains unclear whether the antigenic distances between an individual’s first infection and subsequent exposures dictate disease risk, explaining the observed large-scale differences in dengue hospitalizations across years. Here, we develop a framework that combines detailed antigenic and genetic characterization of viruses with details on hospitalized cases from 21 years of dengue surveillance in Bangkok, Thailand, to identify the role of the antigenic profile of circulating viruses in determining disease risk. We found that the risk of hospitalization depended on both the specific order of infecting serotypes and the antigenic distance between an individual’s primary and secondary infections, with risk maximized at intermediate antigenic distances. These findings suggest that immune imprinting helps determine dengue disease risk and provide a pathway to monitor the changing risk profile of populations and to quantifying risk profiles of candidate vaccines.

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Section: Discussionmentioning

confidence: 99%

Antigenic distance between primary and secondary dengue infections correlates with disease risk

Wang,

Huang,

Katzelnick

et al. 2024

Sci. Transl. Med.

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Bivalent norovirus mRNA vaccine elicits cellular and humoral responses protecting human enteroids from GII.4 infection

Atochina-Vasserman,

Lindesmith,

Mirabelli

et al. 2024

npj Vaccines

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Nucleoside-modified mRNA-LNP vaccines have revolutionized vaccine development against infectious pathogens due to their ability to elicit potent humoral and cellular immune responses. In this article, we present the results of the first norovirus vaccine candidate employing mRNA-LNP platform technology. The mRNA-LNP bivalent vaccine encoding the major capsid protein VP1 from GI.1 and GII.4 of human norovirus, generated high levels of neutralizing antibodies, robust cellular responses, and effectively protected human enteroids from infection by the most prevalent genotype (GII.4). These results serve as a proof of concept, demonstrating that a modified-nucleoside mRNA-LNP vaccine based on norovirus VP1 sequences can stimulate an immunogenic response in vivo and generates neutralizing antibodies capable of preventing viral infection in models of human gastrointestinal tract infection.

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Charting the Impact of Maternal Antibodies and Repeat Exposures on Sapovirus Immunity in Early Childhood From a Nicaraguan Birth Cohort

Bucardo,

Mallory,

González

et al. 2024

The Journal of Infectious Diseases

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Background Sapovirus is an important cause of acute gastroenteritis in childhood. While vaccines against sapovirus may reduce gastroenteritis burden, a major challenge to their development is a lack of information about natural immunity. Methods We measured sapovirus-specific IgG in serum collected, between 2017 and 2020, of mothers soon after delivery and at 6 time points in Nicaraguan children until 3 years of age (n=112 dyads) using virus-like particles representing three sapovirus genotypes (GI.1, GI.2, GV.1). Results Sixteen (14.3%) of the 112 children experienced at least one sapovirus gastroenteritis episode, of which GI.1 was the most common genotype. Seroconversion to GI.1 and GI.2 was most common between 5 and 12 months of age, while seroconversion to GV.1 peaked at 18 to 24 months of age. All children who experienced sapovirus GI.1 gastroenteritis seroconverted and developed genotype-specific IgG. The impact of sapovirus exposure on population immunity was determined using antigenic cartography: newborns share their mothers’ broadly binding IgG responses, which declined at 5 months of age and then increased as infants experienced natural sapovirus infections. Conclusion By tracking humoral immunity to sapovirus over the first 3 years of life, this study provides important insights for the design and timing of future pediatric sapovirus vaccines.

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

Cited by 3 publications

References 97 publications

Antigenic distance between primary and secondary dengue infections correlates with disease risk

Antigenic distance between primary and secondary dengue infections correlates with disease risk

Bivalent norovirus mRNA vaccine elicits cellular and humoral responses protecting human enteroids from GII.4 infection

Charting the Impact of Maternal Antibodies and Repeat Exposures on Sapovirus Immunity in Early Childhood From a Nicaraguan Birth Cohort

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