# Probiotic yeast secreting single-domain antibodies to prevent Clostridium difficile and Campylobacter jejuni disease

> **NIH NIH U19** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $418,645

## Abstract

Abstract
As multidrug-resistant (MDR) bacteria are increasingly difficult to treat and are associated with greater
morbidity and mortality, we are facing a global health crisis. Countermeasures that do not select for drug
resistance are urgently needed. The overall goal of this research program is to develop novel immune-based
preventive strategies against major MDR pathogens in developing and developed countries. In this project we
aim to develop novel probiotic yeast-based immune-interventions against Clostridium difficile and
Campylobacter jejuni, the major causes of bacterial diarrheal and intestinal inflammatory diseases worldwide.
We have developed a novel platform technology against these enteric pathogens by engineering a probiotic
yeast, Saccharomyces boulardii, to secrete multi-specific, single-domain antibodies directly targeting bacterial
virulence factors at the intestinal site of infection. Through our previously funded Centers of Excellence for
Translational Research (CETR) project, we have applied this technology to target C. difficile, and have already
generated a prototype yeast strain that constitutively secretes a tetra-specific, single-domain-antibody (VHH)
fusion which neutralizes the two major C. difficile enterotoxins TcdA and TcdB. A recently completed proof-of-
principle study has shown that oral administration protected mice from both primary and recurrent C. difficile
infection. Building upon these highly encouraging results, we propose to: 1) generate lead S. boulardii strains
secreting multi-specific antibodies against bacterial colonization factors of C. difficile and C. jejuni; 2)
preclinically evaluate the efficacy of the lead strains on reducing bacterial colonization and preventing disease
in animal models; and 3) develop a formulation for drying and encapsulating these lead yeast strains that is
compatible for future use in humans. We envision that our future final products for human use will be enteric
coated capsules containing dried yeast strains, similar to those probiotic S. boulardii products sold over-the-
counter. With the completion of proposed translational activities, we expect to generate a final improved
product of engineered yeast strains to prevent C. difficile disease and a prototype product to prevent C. jejuni
disease. Successful preclinical validation of the lead candidates will also allow further development and large-
scale efforts for eventual commercialization of these products against C. difficile and C. jejuni diseases, for
which we currently have no effective preventative measures.

## Key facts

- **NIH application ID:** 10364713
- **Project number:** 5U19AI142725-04
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Hanping Feng
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $418,645
- **Award type:** 5
- **Project period:** 2019-03-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364713

## Citation

> US National Institutes of Health, RePORTER application 10364713, Probiotic yeast secreting single-domain antibodies to prevent Clostridium difficile and Campylobacter jejuni disease (5U19AI142725-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10364713. Licensed CC0.

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