# Motorized delivery of bacterial antigens to mucosal barriers to enhance immunity against infection

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $197,500

## Abstract

PROJECT SUMMARY/ABSTRACT
Clostridium difficile is a highly threatening pathogen that has risen to prominence as a result of antibiotic overuse
and misuse. The bacteria are particularly rampant in long-term care and hospital settings, where it is responsible
for a significant number of infections. In response to this challenge, researchers are looking into different ways
of managing C. difficile infections. One such strategy that holds significant potential is antivirulence vaccination,
where the body is trained to recognize and neutralize the “weapons” employed by bacteria to colonize their hosts
and proliferate. Despite their promise, these vaccines oftentimes suffer from a lack of efficacy, and their
deployment can also be encumbered by the need for parenteral administration. In this exploratory project, our
goal is to develop an entirely new biomimetic micromotor vaccine that can be orally administered to effectively
protect against C. difficile infection. The platform consists of two key components: (1) a self-propelled magnesium
(Mg)-based micromotor and (2) a macrophage membrane coating that detains bacterial virulence factors. When
combined together, we hypothesize that these motor toxoids will be capable of delivering C. difficile toxins to the
gut’s immune system, where it can elicit potent antibacterial immune responses that protect against subsequent
challenge by the pathogen. By leveraging the natural affinity of toxins for cell membranes, this approach can be
used to immobilize multiple antigens in a nonreversible manner. The Mg core enables the motor toxoids to propel
upon entry into the intestines, and this will promote the active delivery of the antigenic payloads towards the
mucosal barrier, enabling better antigen retention and therefore more efficient immune processing and activation.
To achieve our goals, we will first develop a motor toxoid formulation loaded with C. difficile toxins and evaluate
its characteristics both in vitro and in vivo (Aim 1). Then, in vivo prophylactic efficacy will be evaluated in a murine
model of live C. difficile infection (Aim 2). If successful, this approach for the active delivery of oral vaccines can
be readily applied to other high-priority pathogens by modulating the membrane coating and bacterial antigens
used for synthesis.

## Key facts

- **NIH application ID:** 10370989
- **Project number:** 1R21AI159492-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Ronnie H Fang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $197,500
- **Award type:** 1
- **Project period:** 2022-04-08 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10370989

## Citation

> US National Institutes of Health, RePORTER application 10370989, Motorized delivery of bacterial antigens to mucosal barriers to enhance immunity against infection (1R21AI159492-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10370989. Licensed CC0.

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