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- Brewer-Jensen, Paul D., et al.
(författare)
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Norovirus Infection in Young Nicaraguan Children Induces Durable and Genotype-Specific Antibody Immunity
- 2022
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Ingår i: Viruses. - : MDPI. - 1999-4915. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- 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 provides optimism for pediatric norovirus vaccines administered early in life.
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| 2. |
- Reyes, Yaoska, et al.
(författare)
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Secretor Status Strongly Influences the Incidence of Symptomatic Norovirus Infection in a Genotype-Dependent Manner in a Nicaraguan Birth Cohort
- 2022
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Ingår i: Journal of Infectious Diseases. - : OXFORD UNIV PRESS INC. - 0022-1899 .- 1537-6613. ; 225:1, s. 105-115
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Tidskriftsartikel (refereegranskat)abstract
- Background. The role of histo-blood group on the burden and severity of norovirus gastroenteritis in young infants has not been well documented. Methods. Norovirus gastroenteritis was assessed in 443 Nicaraguan children followed from birth until 3 years of age. Stool samples were tested for norovirus by reverse-transcription quantitative polymerase chain reaction (RT-qPCR), and histo-blood group antigens (HBGAs) were determined by phenotyping of saliva and blood. Hazard ratios and predictors of norovirus acute gastroenteritis (AGE) outcome stratified by HBGA were estimated using Cox proportional hazards models. Results. Of 1353 AGE episodes experienced by children, 229 (17%) tested positive for norovirus with an overall incidence of 21.9/100 child-years. Secretor children were infected as early as 2 months of age and had a higher incidence of norovirus GII compared to nonsecretor children (15.4 vs 4.1/100 child-years, P = .006). Furthermore, all GII.4 AGE episodes occurred in secretor children. Children infected with GI (adjusted odds ratio [aOR], 0.09 [95% confidence interval {CI}, .02-.33]) or non-GII.4 viruses (aOR, 0.2 [95% CI, .07-.6]) were less likely to have severe AGE compared to GII.4-infected children. Conclusions. Secretor status in children strongly influences the incidence of symptomatic norovirus infection in a genogroup or genotype-dependent manner and provides evidence that clinical severity in children depends on norovirus genotypes.
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| 3. |
- Vielot, Nadja A., et al.
(författare)
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First Episodes of Norovirus and Sapovirus Gastroenteritis Protect Against Subsequent Episodes in a Nicaraguan Birth Cohort
- 2022
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Ingår i: Epidemiology. - 1044-3983 .- 1531-5487. ; 33:5, s. 650-653
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Tidskriftsartikel (refereegranskat)abstract
- Background: Norovirus and sapovirus cause a large burden of acute gastroenteritis (AGE) in young children. We assessed protection conferred by norovirus and sapovirus AGE episodes against future episodes.Methods: Between June 2017 and July 2018, we recruited 444 newborns in León, Nicaragua. Weekly household surveys identified AGE episodes over 36 months, and AGE stools were tested by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) for norovirus genogroup (G)I/GII and sapovirus. We used recurrent-event Cox models and negative control methods to estimate protection conferred by first episodes, controlling for observed and unobserved risk factors, respectively.Results: Sapovirus episodes conferred a 69% reduced hazard of subsequent episodes using the negative control method. Norovirus GI (hazard ratio [HR] = 0.67; 95% confidence interval [CI] = 0.31, 1.3) and GII (HR = 0.20; 95% CI = 0.04, 0.44) episodes also appeared highly protective. Protection against norovirus GII was enhanced following two episodes.Conclusions: Evidence of natural immunity in early childhood provides optimism for the future success of pediatric norovirus and sapovirus vaccines.
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