PIPages
Labs

Jimmy Ballard

University of Oklahoma-Health Sciences Center, OK·Microbiology & Immunology

Clostridioides difficile is a bacterium that causes severe diarrheal illness, with recent reports counting over 400,000 cases and nearly 30,000 deaths each year in the United States. Its damage comes largely from toxins it secretes, chief among them TcdB.

Fields

Microbiology & Immunology

Medicine & Clinical Research

Topics

Clostridioides difficile

C. difficile

TcdB

Grants
3 known grants, through Jun 2030

What they work on

  1. Optimize a mutant TcdB toxin that lacks the sequence needed to enter cells, ensuring stability and complete absence of toxicity, and compare its ability to raise neutralizing antibodies against a conventional TcdB toxoid.
  2. Build and test a combination vaccine pairing the TcdB derivative with a polysaccharide antigen from C. difficile, screening candidates for protection in a mouse model and advancing the best to a hamster infection model.
  3. Determine whether C. difficile uses TcdB to inactivate immune cells required for memory responses, by infecting vaccinated animals with strains genetically engineered to express inactive toxin.
  4. Develop and standardize single-infection and repeat-infection mouse challenge models as shared services, controlling housing environment, microbiome, reagents, methods, and readouts so results compare across projects.
  5. Establish a hamster C. difficile challenge model as a core service for testing the most promising vaccination approaches, and make it available to outside investigators.
  6. Select, support, and mentor research project leaders in parasitology, antimicrobial resistance, neuroimmunology, and inflammation, with an Immunology and Informatics Core providing immune profiling and large dataset analysis plus an annual bioinformatics course.

More about the research

A vaccine would be valuable, but there is a catch: the same toxin the vaccine must train the immune system against may also blunt the immune response itself. Work here pursues a next-generation vaccine while testing how far the pathogen can undercut it, backed by standardized animal challenge models and, separately, by a center that builds up early-career microbiologists and immunologists in Oklahoma.

Why it matters

C. difficile causes hundreds of thousands of gastrointestinal infections and tens of thousands of deaths annually, and current treatment often fails to prevent recurrence. A non-toxic TcdB-based vaccine, alone or combined with a bacterial sugar antigen, could offer protection, while understanding how the toxin suppresses immune memory may explain why vaccines underperform. Standardized mouse and hamster challenge models give the wider C. difficile field a common yardstick, and the Oklahoma center trains new infectious disease and immunology investigators whose discoveries could inform future vaccines and treatments.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

Oklahoma Center for Microbial Pathogenesis and Immunity

NIH · Mar 2020 – Jun 2030

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

NIH · Jul 2023 – Jun 2028

Oklahoma C. difficile U19 Challenge Core

NIH · Jul 2023 – Jun 2028

Closest labs

Marcela Pasetti

University of Maryland, Baltimore, MD·Microbiology & Immunology

Optimize process development, formulation and scale-up of two-strain O-polysaccharide conjugates in which Shigella sugar is linked to IpaB, an invasion protein shared across Shigella species, made by cell-free protein expression.

Carol Gilchrist

University of Virginia, VA·Microbiology & Immunology

Optimize the systemic and mucosal immune responses raised by prototype vaccines based on the Cryptosporidium antigens Cp17, Cp23, and CpSMP delivered in liposomes with toll-like receptor agonists, immune-alarm triggers that boost antibody and cellular responses.

Madison Collins

Montana State University, MT·Microbiology & Immunology

Test the hypothesis that molecules controlled by the S. aureus SaeR/S gene regulatory system disrupt autophagy, a self-digestion process that kills trapped microbes, in human neutrophils after they swallow the bacteria.

The school

University of Oklahoma-Health Sciences Center: 11 labs on PI Pages, $474M a year on research, 31 research doctorates a year.

More about University of Oklahoma-Health Sciences Center

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