# A novel vaccination strategy to curb recUTIs

> **NIH NIH R21** · DUKE UNIVERSITY · 2024 · $201,250

## Abstract

ABSTRACT
Urinary tract infections (UTIs) are the second most common bacterial infections in humankind. Women account
for most infections with over 10% of infected subjects experiencing recurrent (rec)UTIs. Because of the high
recurrence rates of UTIs many UTI vaccines are being tested and some are now in clinical trials. However, after
almost three decades of effort, no effective UTI vaccine has yet emerged. Recently, we found that while
antibodies raised against bacterial vaccine antigens are partially effective in clearing bladder bacteria, it is
necessary to recruit pathogen-specific Th1 immune cells into the bladder before bacteria are eradicated. We
found that we could recruit robust numbers of pathogen-clearing CD4 T cells into mouse bladders by
transurethral instillation of a uropathogenic vaccine antigen (FimH) along with a Th1 polarizing adjuvant, CpG
oligodeoxynucleotides. This vaccination strategy was highly protective because in addition to evoking FimH
specific antibodies systemically, they were effective in recruiting pathogen eradicating Th1 cells into the bladder,
potentially preventing future recurrence. Importantly, this vaccine was efficacious in naïve mice but also, in mice
that have already experienced multiple UTIs, representing the population of patients most likely to receive a UTI
vaccine. Before we advance to clinical studies, we seek to undertake additional mouse studies to optimize the
bladder vaccine delivery and to identify appropriate surrogates of protection and vaccine efficacy obtained from
sampling urine and blood that can be deployed even in a limited phase 1 clinical trial. Therefore, the following
specific aims are proposed: (i), examine if bladder vaccination employing vaccine antigen containing
nanoparticles is effective in evoking local protective immunity against UPEC infections in both naïve and thrice
infected mice and (ii), identify surrogates and correlates of protection in mice that can potentially be used to
evaluate bladder vaccination efficacy.

## Key facts

- **NIH application ID:** 10763881
- **Project number:** 5R21AI170985-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Soman N Abraham
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $201,250
- **Award type:** 5
- **Project period:** 2023-01-12 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10763881

## Citation

> US National Institutes of Health, RePORTER application 10763881, A novel vaccination strategy to curb recUTIs (5R21AI170985-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10763881. Licensed CC0.

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