# Antibody Landscape following Human Norovirus Infection and Vaccination

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $767,330

## Abstract

Abstract
Human noroviruses (HuNoV) are the major cause of acute non-bacterial, epidemic gastroenteritis, resulting in
~200,000 deaths/year, mostly in infant, elderly and immunosuppressed groups. HuNoV vaccines are under
development but the results are mixed, in part reflecting antigenic seniority, virus diversity and escape. Our
premise is that the function, epitope specificity and atomic level understanding of the virus type specific and
broadly cross reactive epitopes in the virion that elicit neutralizing antibody will reveal the mechanisms of
protective humoral immunity, which in turn is required for the design of more effective immunogens and
vaccination strategies. Consequently, our program is designed to critically inform the development of broadly
effective HuNoV vaccines that target highly prevalent, medically important genogroup II strains (GII.4 and GII.2).
To achieve these goals, we have relevant time-ordered sample sets from cohorts of vaccinated individuals,
natural infections and human challenge studies which are leveraged throughout the program to elucidate the
fundamental mechanisms governing protective immunity, virus escape and pandemic strain emergence. We
have also assembled a complementary group of renown experts to elucidate the essential issues in HuNoV
serological immunity, identify the key neutralizing epitopes targeted by type specific and broadly protective
immunity, and reveal the molecular mechanisms governing HuNoV neutralization, antigenic seniority and broad
protective immunity. Moreover, the program is designed to translate these novel findings to improved 2nd
generation structure-guided HuNoV vaccine immunogens which are designed to improve the breadth and
durability of humoral immune responses associated with protective immunity. To achieve these goals, the
program has three specific aims. In aim 1, we will define the HuNoV-specific serological antibody repertoire and
produce recombinant antibodies for detailed structure and molecular analyses. In aim 2, we identify type specific
and broadly cross neutralizing antibodies and use molecular approaches to identify key interacting epitopes. In
aim 3, we will solve the atomic level structure of several relevant antibodies with the P domain of the capsid
protein to delineate the structural basis for HBGA blockade and neutralization and use structure-guided
strategies to increase immunogenic breadth and antigen stability, leading to improved vaccine function in vivo.

## Key facts

- **NIH application ID:** 9862657
- **Project number:** 1R01AI148260-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Ralph S Baric
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $767,330
- **Award type:** 1
- **Project period:** 2020-03-05 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9862657

## Citation

> US National Institutes of Health, RePORTER application 9862657, Antibody Landscape following Human Norovirus Infection and Vaccination (1R01AI148260-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9862657. Licensed CC0.

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