# Enhancing C. difficile vaccination in the context of TcdB-mediated immunosuppression.

> **NIH NIH U19** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2024 · $375,372

## Abstract

PROJECT SUMMARY (Project 1)
The most recent reports indicate Clostridioides difficile is the cause of over 400,000 cases of gastrointestinal
illness and nearly 30,000 deaths annually. The goals of this project are to develop an effective next generation
vaccine to prevent C. difficile disease and investigate the virulence-related activities of C. difficile that might
reduce vaccine effectiveness. A leading candidate developed for vaccination in the Ballard lab is a mutant of
TcdB lacking a key cell entry sequence. This mutant is unable to interact with cells but appears to retain aspects
critical to promoting a neutralizing antibody response. This vaccine candidate will be further optimized and
modified to ensure stability and a total absence of toxicity. Comparisons will be made between this mutant and
a toxoid of TcdB. Next, the TcdB derivative will be used in combination with a polysaccharide antigen derived
from C. difficile to generate a novel combination vaccine. All vaccine candidates will be tested for protection
against C. difficile disease in a mouse model and the most promising of those will be further tested in a hamster
model of infection. Using strains of C. difficile genetically engineered to express inactive TcdB, we will also
determine if C. difficile inactivates key immune cells needed to provide effective memory responses in vaccinated
animals. Together, these studies will both identify new C. difficile vaccines and determine the extent to which
this pathogen can subvert their effectiveness.

## Key facts

- **NIH application ID:** 10892824
- **Project number:** 5U19AI174994-02
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Jimmy D. Ballard
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $375,372
- **Award type:** 5
- **Project period:** 2023-07-25 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892824

## Citation

> US National Institutes of Health, RePORTER application 10892824, Enhancing C. difficile vaccination in the context of TcdB-mediated immunosuppression. (5U19AI174994-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10892824. Licensed CC0.

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