Human norovirus is the leading cause of acute gastroenteritis globally causing up to 200,000 deaths per year. However, there are no antiviral drugs or vaccines. We use the closely related mouse or murine norovirus (MNV) as a model system to understand how human norovirus causes infection and disease.

$641,093

Human noroviruses (HNoVs) are medically important non-enveloped positive-sense RNA viruses that cause gastroenteritis. This revised proposal leverages the recent discovery of CD300lf as a receptor for murine NoV (MNoV, Science 2016 353:933) to define mechanisms of NoV pathogenesis, persistence and intestinal immunity.

$699,874

This K24 proposal builds upon a decade of clinical and epidemiologic research on childhood gastroenteritis in Nicaragua by the candidate, Sylvia Becker-Dreps, MD, MPH. As a natural extension of Dr. Becker-Dreps' previous work on understanding reduced rotavirus vaccine effectiveness in resource-constrained settings, the current proposal expands Dr. Becker-Dreps' skillsets to allow her to contribute to the development of an effective pediatric norovirus vaccine.

$168,497

The purpose of this proposal is to determine the breadth of T-cell responses to norovirus, as well as the stability of norovirus epitopes in circulating viruses. By classifying T-cells responses to norovirus, we hope to enable clinical trials of adoptive T-cell immunotherapy for chronic norovirus infections in immunocompromised hosts, and also to aid in future design of norovirus vaccines.

$89,250

We continued an epidemiological investigation of noroviruses in immunocompromised patients enrolled in research protocols at the NIH Clinical Research Center. A multiplex assay for the detection of bacterial, viral, and parasitic gastrointestinal pathogens became available for use in the Clinical Center near the end of 2015. In collaboration with epidemiologists in NIAID we explored the relative contribution of viral pathogens to diarrheal illness since its employment.

$1,871,553

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.

$739,405

Animal viruses share two important features; a) an efficient system for delivering their genome to the target cell usually involving an activation process in the virion and b) a means of interacting with the adaptive immune system of the host. The structural and biophysical studies detailed here will show how the noroviruses have evolved capsids that perform both functions.

$559,337

Narrative Human norovirus and Clostridium difficile are the leading causes of acute gastroenteritis with significant morbidity and mortality. To date there is still no single vaccine available on the market. The goal of this project is to develop a novel oral passive immunoprophylactic strategy to prevent the infections and diseases associated with the two pathogens.

$647,849