# Project 3: Defining adaptive immune interactions that shape Clostridioides difficile infection

> **NIH NIH U19** · UNIVERSITY OF PENNSYLVANIA · 2024 · $359,600

## Abstract

SUMMARY: PROJECT 3 - IMMUNOLOGY
The quality of the host immune response to Clostridioides difficile infection is one of the strongest predictors of
disease severity. Despite the protective capacity of the host immune response, the immune parameters that
promote immunity remain poorly understood. Approximately 25-35% of patients that recover from primary C.
difficile infection will experience a recurrence episode indicating the host often fails to develop natural immunity
following primary infection. Further, multiple vaccine trails have not met primary endpoint of reducing
occurrence of infection despite the vaccine candidates eliciting robust antibody responses against C. difficile
toxins, the primary virulence factors driving disease. A limited mechanistic understanding of why the
natural immune response to infection often does not promote immunity represents a critical roadblock
toward the goal of developing a vaccine that will elicit lasting protective immunity in high-risk
populations. This project will systematically evaluate the natural immune response to C. difficile infection
using both patient sample and a murine infection system. In aim 1 we will compare the capacity of the systemic
and intestinal mucosal antibodies elicited following infection to detect and bind to C difficile residing in the
intestinal lumen. Successful generation of an antibody response that targets C. difficile in the intestinal tract is
dependent on a coordinated C. difficile-specific CD4+ T and B cell response in the intestine and associated
draining lymph nodes and is the focus of studies proposed in aim 2. Last, in aim 3 we will investigate the in
vivo biogeography and transcriptome of C. difficile in the presence of adaptive immune pressure to identify
immune evasion mechanisms employed by C. difficile to promote persistence and transmission. The result of
all three aims will feedback into Project 1 (Vaccine Development) to inform mRNA vaccine studies by
providing a template how vaccine-induced immunity can be shaped to limit disease, prevent colonization, and
recurrence of C. difficile.
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## Key facts

- **NIH application ID:** 10792902
- **Project number:** 5U19AI174998-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Michael C. Abt
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $359,600
- **Award type:** 5
- **Project period:** 2023-03-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10792902

## Citation

> US National Institutes of Health, RePORTER application 10792902, Project 3: Defining adaptive immune interactions that shape Clostridioides difficile infection (5U19AI174998-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10792902. Licensed CC0.

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