4.6 Article

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

Journal

VIRUSES-BASEL
Volume 14, Issue 9, Pages -

Publisher

MDPI
DOI: 10.3390/v14092053

Keywords

norovirus; immunity; diarrhea; gastroenteritis; children; Nicaragua; blockade antibody

Categories

Funding

  1. National Institute of Allergy and Infectious Diseases (NIAID) [K24AI141744, R01AI127845, R01AI148260]
  2. NIH-Fogarty International Center [203268/Z/16/Z]
  3. [D43TW010923]

Ask authors/readers for more resources

The development of a pediatric norovirus vaccine faces significant challenges due to the diverse strains infecting young children. This study found that the first natural norovirus gastroenteritis episodes in young children were dominated by a limited number of genotypes and induced genotype-specific antibody responses. This suggests that an effective pediatric norovirus vaccine would likely need to be multivalent and include globally dominant genotypes. The study also found that the protection from natural infections lasted for a significant duration, providing optimism for early administration of pediatric norovirus vaccines.
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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available