# Development of rotavirus-based enterotoxigenic Escherichia coli dual vaccines

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2024 · $155,500

## Abstract

Project Summary
 Diarrheal diseases account for 1 in 10 child deaths worldwide. Rotavirus (RV) and enterotoxigenic
Escherichia coli (ETEC) are major etiological causes of acute gastroenteritis and severe diarrhea worldwide,
together resulting in approximately 300,000 deaths each year, mostly in children under the age of five. Current
RV vaccines have limited efficacy in endemic countries and no direct antivirals are available. No vaccine is
licensed for ETEC. Our overall objectives are to better understand the biology of RV and ETEC and to use that
information to develop therapeutic interventions to alleviate diarrhea and sequelae.
 In preliminary studies, we utilized an improved RV reverse genetics system developed by our lab and
generated a recombinant murine RV that encodes the protruding domain of the human norovirus VP1 protein.
We found that this RV-based viral vector induces a robust antigen-specific serum IgG and fecal IgA responses
in inoculated mouse pups. Based on these data, we constructed several new recombinant RVs that express
ETEC heat-labile and heat-stable toxins. We hypothesize that one or more novel RV-ETEC dual vaccine
candidates will induce a protective humoral immune response in mice and reduce pathogen burden
and pathogenesis from subsequent RV and ETEC infections.
 To test this hypothesis, we have developed a highly tractable murine RV reverse genetics method, disease
relevant neonatal and adult mouse models, and several innovative primary human small bowel organoid
cultures, which will provide an unprecedented resolution of understanding of the immunogenicity and protective
efficacy of our vaccine candidates. In Aim 1, we will characterize RV replication and define the immunological
responses of our dual vaccines in neonatal mice. In Aim 2, we will examine the efficacy of the recombinant RV-
ETEC dual vaccines in protecting immunized mice from RV and ETEC challenges in adult mice. Collectively,
we expect our proof-of-principle study to start to establish the utility of RVs as an innovative live-attenuated
mucosal vaccine platform to encode foreign antigens and broadly protect against common enteric pathogens.

## Key facts

- **NIH application ID:** 10908655
- **Project number:** 5R21AI173598-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Siyuan Ding
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $155,500
- **Award type:** 5
- **Project period:** 2023-08-16 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908655

## Citation

> US National Institutes of Health, RePORTER application 10908655, Development of rotavirus-based enterotoxigenic Escherichia coli dual vaccines (5R21AI173598-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10908655. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*