# Characterization of the T-cell Response to Human Norovirus Infection

> **NIH NIH R03** · CHILDREN'S RESEARCH INSTITUTE · 2021 · $89,250

## Abstract

Abstract
Chronic norovirus infection can cause chronic diarrhea and wasting in immunocompromised patients, including
those undergoing hematopoietic stem cell transplantation and with primary immunodeficiency disorders. There
are currently no available therapies to treat norovirus. Our preliminary data demonstrates that healthy
individuals have T cell immunity against norovirus, and that identified viral epitopes in antigens NS6 and VP1
are well conserved across viral genotypes. The overarching goal of this proposal is the development of a novel
treatment for chronic norovirus infection in patients undergoing HSCT. In our previous study, we demonstrated
safety and potential efficacy of virus-specific T cells targeting CMV, EBV, and adenovirus as well as the
feasibility of this approach. Knowledge of T-cell response to norovirus could enable future trials of adoptive
immunotherapy with NSTs, which represents a novel antiviral therapy that could provide long-term protection
against norovirus. To classify the T-cell response against norovirus we now propose to take blood from the
healthy donors and expand and enrich the norovirus-specific T cells (NSTs) present in donors' blood, followed
by extensive characterization of the function of NSTs. We hypothesize that the infusion of NSTs will be safe
and effective against norovirus infections in patients post HSCT, and will restore lasting immunity against
norovirus. We further hypothesize that norovirus epitopes will correlate with expansion of T cells recognizing
immunodominant viral epitopes, which will correspond to stable regions of the viral genome. Through this
study, we will address the following specific aims: 1) To determine whether norovirus specific T cells recognize
a broad number of MHC Class I and class II restricted epitopes, and 2) To evaluate whether norovirus epitope
specific T cells are cross-reactive with a broad panel of isolates encompassing multiple viral strains.
Collectively, these aims will identify the range and stability of norovirus epitopes. Completion of this study could
provide a novel antiviral therapy which could reduce virus-associated morbidity in HSCT, and will guide future
cellular therapy and vaccine trials targeting enteric viruses.

## Key facts

- **NIH application ID:** 10174735
- **Project number:** 5R03AI153917-02
- **Recipient organization:** CHILDREN'S RESEARCH INSTITUTE
- **Principal Investigator:** Michael Daniel Keller
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $89,250
- **Award type:** 5
- **Project period:** 2020-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10174735

## Citation

> US National Institutes of Health, RePORTER application 10174735, Characterization of the T-cell Response to Human Norovirus Infection (5R03AI153917-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10174735. Licensed CC0.

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