# Identifying the Breadth of Antibody Responses to Clostridioides difficile Infection

> **NIH NIH R03** · LURIE CHILDREN'S HOSPITAL OF CHICAGO · 2021 · $78,385

## Abstract

PROJECT SUMMARY ABSTRACT
Clostridioides (Clostridium) difficile infection (CDI) is a common healthcare-associated infection in US children
and adults. CDI, which ranges from mild diarrhea to life-threatening colitis, is associated with substantial
morbidity, mortality, and excess healthcare expenditures. The CDC has classified C. difficile as an “immediate
public health threat that requires urgent and aggressive action.” This call to action has expanded CDI
investigation and prompted efforts to develop novel and more effective prevention strategies. Immunological
agents are a promising strategy for CDI prevention; a monoclonal antibody against C. difficile is recently FDA
approved for CDI prevention, and several toxin-based vaccines are in clinical development. Despite these
products showing promise for CDI prevention, many patients have failed these therapies. The immunizations
currently under clinical investigation were developed based on knowledge of C. difficile immunogenicity in
animals, which may not adequately represent C. difficile immunogenicity in humans. To better understand the
relative immunogenicity of C. difficile antigens in humans, we propose characterization of the plasmablast
response following natural CDI. Plasmablasts are plasma cell precursors that produce antibodies directed
against a pathogen; antigen-specific plasmablasts can be isolated from peripheral blood 1-3 weeks after
infection. Antibodies encoded by these cells can be produced in vitro and the target antigens identified. This
innovative method has been recently successfully applied to other infectious diseases, including to Kawasaki
Disease by our research team. By analyzing the plasmablast response following CDI, we will identify the
breadth of the human antibody response to C. difficile infection. We hypothesize that the antibody response to
C. difficile is not limited to toxin antigens, and that antibodies against both toxin and non-toxin antigens provide
protection against CDI. Specifically, in this feasibility study, we aim to identify and clone the peripheral blood
plasmablast response following CDI in 3 children and 3 adults, and identify C. difficile antigenic targets of
oligoclonal post-CDI plasmablasts using various proteomics analyses. Knowledge gained in this feasibility
study will inform design of larger studies to validate immunogenicity of C. difficile antigens in a more diverse
patient cohort and the neutralizing ability of these antibodies across a diverse set of C. difficile strain types. In
future studies, we will determine the specific toxin and non-toxin epitopes recognized by antibodies following
natural CDI in humans, and we will study how antibody responses to C. difficile toxin and non-toxin antigens
impact C. difficile colonization and infection. Identification of broadly immunogenic antigens will guide future
work to investigate potential immunization candidates to prevent CDI and colonization. Our research team and
the Northwestern Univ...

## Key facts

- **NIH application ID:** 10186695
- **Project number:** 5R03AI149000-02
- **Recipient organization:** LURIE CHILDREN'S HOSPITAL OF CHICAGO
- **Principal Investigator:** LARRY K KOCIOLEK
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $78,385
- **Award type:** 5
- **Project period:** 2020-06-09 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10186695

## Citation

> US National Institutes of Health, RePORTER application 10186695, Identifying the Breadth of Antibody Responses to Clostridioides difficile Infection (5R03AI149000-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10186695. Licensed CC0.

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