# Oral Immunotherapy with IgA to Treat C. difficile Infection

> **NIH NIH R44** · SECRETORY IGA, INC. · 2022 · $892,325

## Abstract

Abstract
Clostridioides difficile infection, the cause of antibiotic-associated
pseudomembraneous colitis, is a growing national health problem. The incidence
of primary C. difficile-infection in the hospitalized U.S. population is >300,000
cases annually. There is a high incidence of relapse. For these reasons there is
an urgent need for new non-antibiotic based therapeutic approaches to treat this
potentially life threatening disease. The novel therapeutic approach proposed in
this application is an orally administered immunotherapy consisting of polyclonal
human monomeric and secretory IgA (sIgA) formed by the innovative technical
process of combining plasma derived dimeric IgA with recombinant human
secretory component. This innovative immunotherapy will provide a significant
clinical advantage over passive immunization with parenterally administered
recombinant monoclonal and polyclonal IgG antibodies. Proof of Principle is
established. We have demonstrated that plasma derived sIgA provides a
survival advantage to hamsters infected with C. difficile and treated with a
subtherapeutic dose of vancomycin. Others have found that plasma derived sIgA
was effective in preventing relapse of C. difficile disease in a mouse model. The
long-term goal of this project is to commercialize orally administered
semisynthetic human secretory immunoglobulin A for the treatment of C. difficile
infection. The Specific Aims are: 1) Determine the minimal dose of orally
administered IgA and sIgA that is an effective prophylactic treatment in the
hamster model of C. difficile disease. 2) Determine whether orally administered
human IgA- sIgA mixture results in any toxicity in a 2 week mouse toxicity model.
3) Assess the intestinal microbiome of mice before and after treatment with sIgA.
4) Determine whether orally administered IgA and sIgA is effective when
treatment begins after the C. difficile spore challenge. 5. Evaluate the stability of
plasma derived IgA and sIgA during storage. 6: Determine whether there is
systemic absorption of orally administered human IgA. 7. Establish GLP level
Standard Operating Procedures (SOP) for purity and identity of product batches.
and 8) Transfer production methods to Emergent BioSolutions, a contract
development and manufacturing organization (CDMO) for scale-up.

## Key facts

- **NIH application ID:** 10476775
- **Project number:** 1R44DK130749-01A1
- **Recipient organization:** SECRETORY IGA, INC.
- **Principal Investigator:** Stephen C Brown
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $892,325
- **Award type:** 1
- **Project period:** 2022-04-14 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10476775

## Citation

> US National Institutes of Health, RePORTER application 10476775, Oral Immunotherapy with IgA to Treat C. difficile Infection (1R44DK130749-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10476775. Licensed CC0.

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