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Norovirus Infection in Young Nicaraguan Children Induces Durable and Genotype-Specific Antibody Immunity

Title: Norovirus Infection in Young Nicaraguan Children Induces Durable and Genotype-Specific Antibody Immunity
Authors: Brewer-Jensen, Paul D.; Reyes, Yaoska; Becker-Dreps, Sylvia; Gonzalez, Fredman; Mallory, Michael L.; Gutierrez, Lester; Zepeda, Omar; Centeno, Edwing; Vielot, Nadja; Diez-Valcarce, Marta; Vinje, Jan; Baric, Ralph; Lindesmith, Lisa C.; Bucardo, Filemon
Publisher Information: Linköpings universitet, Avdelningen för molekylär medicin och virologi; Linköpings universitet, Medicinska fakulteten; Univ N Carolina, NC 27599 USA; Natl Autonomous Univ Nicaragua, Nicaragua; Univ N Carolina, NC 27599 USA; Univ N Carolina, NC 27599 USA; US Ctr Dis Control & Prevent, GA 30329 USA; MDPI
Publication Year: 2022
Collection: Linköping University Electronic Press (LiU E-Press)
Subject Terms: norovirus; immunity; diarrhea; gastroenteritis; children; Nicaragua; blockade antibody; Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology); Molecular Biology; Microbiology; Biochemistry or Biopharmacy); Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi); molekylärbiologi; mikrobiologi; biokemi eller biofarmaci)
Description: There are significant challenges to the development of a pediatric norovirus vaccine, mainly due to the antigenic diversity among strains infecting young children. Characterizing human norovirus serotypes and understanding norovirus immunity in naive children would provide key information for designing rational vaccine platforms. In this study, 26 Nicaraguan children experiencing their first norovirus acute gastroenteritis (AGE) episode during the first 18 months of life were investigated. We used a surrogate neutralization assay that measured antibodies blocking the binding of 13 different norovirus virus-like particles (VLPs) to histo-blood group antigens (HBGAs) in pre- and post-infection sera. To assess for asymptomatic norovirus infections, stools from asymptomatic children were collected monthly, screened for norovirus by RT-qPCR and genotyped by sequencing. Seroconversion of an HBGA-blocking antibody matched the infecting genotype in 25 (96%) of the 26 children. A subset of 13 (50%) and 4 (15%) of the 26 children experienced monotypic GII and GI seroconversion, respectively, strongly suggesting a type-specific response in naive children, and 9 (35%) showed multitypic seroconversion. The most frequent pairing in multitypic seroconversion (8/12) were GII.4 Sydney and GII.12 noroviruses, both co-circulating at the time. Blocking antibody titers to these two genotypes did not correlate with each other, suggesting multiple exposure rather than cross-reactivity between genotypes. In addition, GII titers remained consistent for at least 19 months post-infection, demonstrating durable immunity. In conclusion, the first natural norovirus gastroenteritis episodes in these young children were dominated by a limited number of genotypes and induced responses of antibodies blocking binding of norovirus VLPs in a genotype-specific manner, suggesting that an effective pediatric norovirus vaccine likely needs to be multivalent and include globally dominant genotypes. The duration of protection from natural infections ...
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: Viruses, 2022, 14:9; PMID 36146859; ISI:000859078200001
DOI: 10.3390/v14092053
Availability: http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-189102; https://doi.org/10.3390/v14092053
Rights: info:eu-repo/semantics/openAccess
Accession Number: edsbas.2CAFCBCD
Database: BASE