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Published on: February 19, 2013
Protection of Mice Orally Infected With Shiga Toxin-Producing Citrobacter rodentium Treated With Nanobody Multimer
Abhineet Sheoran1, Amanda J Martinot1, Sally R Robinson1
1Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, USA.
Open Forum Infectious Diseases
|June 26, 2026
Summary
A novel nanobody treatment completely protected mice from Shiga toxin-producing Escherichia coli (STEC) infection complications, even when given days after exposure. This offers hope for treating STEC-associated hemolytic-uremic syndrome (HUS).
Area of Science:
- Microbiology
- Immunology
- Toxicology
Background:
- Shiga toxin-producing Escherichia coli (STEC) causes gut infections and can lead to hemolytic-uremic syndrome (HUS), especially in young children.
- STEC infections expressing Stx2 variants are a significant risk factor for HUS, a severe condition with no specific treatment.
- A therapeutic window exists between STEC diarrhea onset and HUS development, offering an opportunity for intervention.
Purpose of the Study:
- To develop and test a novel therapeutic agent for STEC infections and associated HUS.
- To evaluate the efficacy of a Stx-neutralizing nanobody in a preclinical model of STEC infection.
Main Methods:
- A mouse model of STEC infection was established using genetically modified Citrobacter rodentium expressing Stx2d.
- Mice were treated with a Stx-neutralizing nanobody multimer fused to an IgG1 Fc domain (VNA2-Stx/hFc).
- Treatment was administered intraperitoneally, with timing assessed relative to bacterial challenge.
Main Results:
- A single dose of VNA2-Stx/hFc administered up to 4 days post-infection, within the potential human intervention window, provided complete protection in mice.
- The model successfully replicated key features of human STEC infections, including mucosal lesions and systemic kidney damage.
Conclusions:
- The developed mouse model effectively mimics human STEC infections and associated HUS, serving as a valuable tool for evaluating treatments.
- The Stx-neutralizing nanobody (VNA2-Stx/hFc) demonstrated significant therapeutic potential against STEC-HUS.
- This therapeutic approach shows promise for being safe, simple, and cost-effective to manufacture.
