# Intestinal microbiota-mediated rotavirus vaccine failure

> **NIH NIH R01** · GEORGIA STATE UNIVERSITY · 2024 · $783,735

## Abstract

PROJECT SUMMARY
Infection of gut epithelia by attenuated rotavirus (RV) vaccines serves to protect millions of lives annually. It is
increasingly appreciated that gut microbiota, which shape the milieu in which rotaviruses encounter the
epithelium is a pivotal determinant of rotavirus vaccine efficacy. Indeed, RV vaccines have proven to be much
less effective in developing countries which are known to have stark differences in gut microbiota composition.
Our published work demonstrates that microbiota can both directly impact RV and, moreover, impact gut
epithelia to prevent against its entry and replication. Furthermore, our unpublished work compellingly argues for
a central role for gut microbiota composition in RV vaccine inefficacy. Specifically, we find that transplant of
microbiota from non-RV vaccine responding children confers a microbiota-dependent non-responder phenotype.
In addition, culturing infant fecal samples in bioreactor continuous culture systems yields supernatants that
differentially inhibit RV vaccine replication in vitro. Hence, the central goals of this proposal are to identify and
isolate microbiota constituents that drive RV vaccine inefficacy in humans and determine mechanisms by which
they act. Findings from this work will advance our fundamental knowledge on bacterial-viral interactions in the
gut, mechanistically enlighten how microbiota can impact replication and response to live, attenuated oral
vaccines and potentially aid in the development of novel strategies to reduce the burden of enteric viral infections.

## Key facts

- **NIH application ID:** 10892170
- **Project number:** 5R01AI170014-03
- **Recipient organization:** GEORGIA STATE UNIVERSITY
- **Principal Investigator:** Andrew T Gewirtz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $783,735
- **Award type:** 5
- **Project period:** 2022-09-19 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892170

## Citation

> US National Institutes of Health, RePORTER application 10892170, Intestinal microbiota-mediated rotavirus vaccine failure (5R01AI170014-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10892170. Licensed CC0.

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