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Characterizing human norovirus serotypes and understanding norovirus immunity in na\u00efve 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 na\u00efve 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 provides optimism for pediatric norovirus vaccines administered early in life.<\/jats:p>","DOI":"10.3390\/v14092053","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:08:09Z","timestamp":1663718889000},"page":"2053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Norovirus Infection in Young Nicaraguan Children Induces Durable and Genotype-Specific Antibody Immunity"],"prefix":"10.3390","volume":"14","author":[{"given":"Paul D.","family":"Brewer-Jensen","sequence":"first","affiliation":[{"name":"Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoska","family":"Reyes","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medical Sciences, National Autonomous University of Nicaragua, Le\u00f3n 21000, Nicaragua"},{"name":"Division of Molecular Medicine and Virology, Department of Clinical and Experimental Medicine, Link\u00f6ping University, SE-581 83 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Becker-Dreps","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"Department of Family Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredman","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medical Sciences, National Autonomous University of Nicaragua, Le\u00f3n 21000, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0768-572X","authenticated-orcid":false,"given":"Michael L.","family":"Mallory","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lester","family":"Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medical Sciences, National Autonomous University of Nicaragua, Le\u00f3n 21000, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Zepeda","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medical Sciences, National Autonomous University of Nicaragua, Le\u00f3n 21000, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5786-5502","authenticated-orcid":false,"given":"Edwing","family":"Centeno","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medical Sciences, National Autonomous University of Nicaragua, Le\u00f3n 21000, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9004-0609","authenticated-orcid":false,"given":"Nadja","family":"Vielot","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2247-0332","authenticated-orcid":false,"given":"Marta","family":"Diez-Valcarce","sequence":"additional","affiliation":[{"name":"Division of Viral Diseases, U.S. Centers for Disease Control and Prevention, Atlanta, GA 30329, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Vinj\u00e9","sequence":"additional","affiliation":[{"name":"Division of Viral Diseases, U.S. Centers for Disease Control and Prevention, Atlanta, GA 30329, 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Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S1473-3099(14)70767-4","article-title":"Global prevalence of norovirus in cases of gastroenteritis: A systematic review and meta-analysis","volume":"14","author":"Ahmed","year":"2014","journal-title":"Lancet Infect. 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