# Preventing norovirus and Clostridium difficile gastroenteritis by engineered probiotic yeast Saccharomyces boulardii secreting multi-specific single-domain antibodies

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $600,213

## Abstract

Abstract
Human norovirus (hNoV) and Clostridium difficile (CD) represent two leading causes of acute gastroenteritis
worldwide with significant morbidity and mortality. The two infections (one viral and one bacterial) share many of
the same characteristics of transmission; and concurrent infections are particularly prevalent in the US in high-
risk populations, such as aged patients undergoing antibiotic treatments, hospitalized patients, or patients
staying in long-term care facilities. Despite great efforts in the development of vaccines against both infections,
to date there is still no single vaccine available on the market. We have developed a novel platform technology
against enteric bacterial pathogens by engineering a probiotic yeast, Saccharomyces boulardii, to secrete multi-
specific single-domain (VHH) antibodies, directly targeting bacterial virulence factors at the intestinal site of
infection. We have successfully applied this technology to target Clostridium difficile. The overall objective of this
project is to generate Sb strains secreting mSdAbs against both CD toxins and hNoV, generate proof-of-principle
efficacy data in relevant animal disease models, and develop clinic-compatible formulations for drying and
encapsulating the Sb-mSdAb strains. We hypothesize that oral administration of Sb-mSdAb strains secreting
mSdAb against hNoV and CD toxins will prevent their individual or concurrent infections. To test this hypothesis,
we propose to accomplish the following 3 specific aims: 1) Engineer Sb-mSdAb strains (Sb-aNoVCd) secreting
VHH fusions against both CD toxins and hNoVs. 2) Determine preventive efficacy of Sb-aNoVCd strains against
infections with hNoV and CD in gnotobiotic pigs. 3) Develop a formulation supporting yeast spray drying and
encapsulation. With the completion of proposed translational activities, we will have generated lead Sb-aNoVCd
strains and evaluated in vivo characteristics in mice and in gnotobiotic pigs which is the most appropriate animal
model of hNoV infection and disease. Should the key proof-of-principle efficacy data generated, future scale-up
efforts will be justified to include additional VHHs for generating broadly efficacious lead immunoprophylactic
strains and eventual commercialization of the yeast products against CD and hNoV gastroenteritis for which we
currently have no prophylaxis or vaccines.

## Key facts

- **NIH application ID:** 10087883
- **Project number:** 5R01AI148357-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Hanping Feng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $600,213
- **Award type:** 5
- **Project period:** 2020-01-22 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10087883

## Citation

> US National Institutes of Health, RePORTER application 10087883, Preventing norovirus and Clostridium difficile gastroenteritis by engineered probiotic yeast Saccharomyces boulardii secreting multi-specific single-domain antibodies (5R01AI148357-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10087883. Licensed CC0.

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