# Characterization of neutralizing antitoxins and epitopes in Clostridium difficile patients

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $386,250

## Abstract

Abstract
Intestinal injury and inflammation in Clostridium difficile infection (CDI), an increasing cause of morbidity,
mortality and financial cost in the US, is mediated by two large clostridial toxins: TcdA & TcdB. Although
antibodies against each toxin have been shown to be associated with protection, it is unclear what types of
antibodies and their epitopes are responsible for effective immunity against CDI in patients. The goal of this
project is to define the characteristics of a protective humoral immune response in CDI and the major
neutralizing TcdA & TcdB epitopes. The hypothesis is that host antibodies directed against major neutralizing
epitopes in TcdA & TcdB confer protection against CDI. To test this hypothesis, we will first validate our
preliminary finding on neutralizing anti-TcdA/TcdB responses that correlate protection against severe CDI will
also correlate protection against recurrence (Aim 1); subsequently we will characterize C. difficile toxin-specific
B cell responses at clonal level and correlate these with CDI disease progression and recurrence (Aim 2); and
finally we will clone neutralizing antibodies from individual B cells to obtain a representative panel of human
protective monoclonal antibodies against the two toxins and characterize their binding epitopes and reactivity
to a variety of toxins produced by major C. difficile endemic and outbreak strains (Aim 3). The completion of
these specific aims can lead to the discovery of antibody biomarkers that predict outcomes of the most
significant clinical issues in CDI management, including CDI occurrence, severity, and recurrence.
Identification and characterization of protective antibodies may also facilitate the development of novel passive
immunotherapy and vaccine approaches.

## Key facts

- **NIH application ID:** 9862062
- **Project number:** 1R01AI148270-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Hanping Feng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $386,250
- **Award type:** 1
- **Project period:** 2020-01-16 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9862062

## Citation

> US National Institutes of Health, RePORTER application 9862062, Characterization of neutralizing antitoxins and epitopes in Clostridium difficile patients (1R01AI148270-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9862062. Licensed CC0.

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