# Determinants of humoral immunity to norovirus in children

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $247,425

## Abstract

ABSTRACT
Noroviruses are now the leading cause of viral gastroenteritis in children. Development of pediatric norovirus
vaccines is underway, yet little is currently known about the development of humoral immunity against norovirus
in children. We aim to help close this gap by defining how natural infection primes pediatric humoral immunity at
the serological and B cell levels. This work generates new immunological tools to understand the development
of norovirus immunity, and leverages samples being collected from an existing birth cohort study in Nicaragua
(R01AI127845-03, Becker-Dreps/Vinje: Natural history, immunity and transmission patterns of sapovirus in a
Nicaraguan birth cohort). First, we will characterize and compare memory B cell repertoires after first and second
norovirus infections of the same genogroup in three previously naïve children. From these primary and
secondary infections, we will generate stable populations of B cells to determine frequencies, specificities, and
function of corresponding antibodies. Functional assays will be performed by assessing histo-blood group
antigen (HBGA) blockade to a panel of diverse noroviruses. These studies will enable us to determine whether
primary exposure to norovirus elicits broadly-active antibodies against a range of norovirus genotypes, or if
immunity is genotype-specific, and how the breath of the response changes after secondary infection. Following
second infections, we will examine whether the predominant response is to pre-existing norovirus strains or to
the newly-infecting strain, to better understand how primary infections shape the immune response to
subsequent infections. This will provide insight into the question of whether antigenic seniority (boosting of pre-
existing immunity to an ancestral strain) may be occurring, as has been shown in previously-infected adults
receiving a norovirus vaccine candidate [Lindesmith, et al. 2015 PLoSMed]. Next, we will clone norovirus-specific
pediatric mAbs that are found to have HBGA blocking activity from these natural infections. Of highest utility to
vaccine development, we will use these mAb to map epitopes targeted in natural GII.4 infections. We posit that
epitopes targeted by natural infection may be important to include in pediatric norovirus vaccines, to best mimic
the development of natural immunity to norovirus. Overall, a better understanding of priming to norovirus in naïve
individuals is now needed to inform the design and schedule of pediatric norovirus vaccines. This project would
provide the most in-depth view to date of B cell stimulation and antibody specificity following norovirus infection
in naïve children.

## Key facts

- **NIH application ID:** 9970716
- **Project number:** 1R21AI152039-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Sylvia Irene Becker-Dreps
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $247,425
- **Award type:** 1
- **Project period:** 2020-03-09 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970716

## Citation

> US National Institutes of Health, RePORTER application 9970716, Determinants of humoral immunity to norovirus in children (1R21AI152039-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9970716. Licensed CC0.

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