# Harnessing Antibody Responses to Prevent and Treat Urinary Tract Infections

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $630,335

## Abstract

SUMMARY
Urinary tract infections (UTIs) affect 15 million women in the United States every year and treatment for UTIs is
becoming more difficult due to high rates of antibiotic resistance. Further, UTIs are highly recurrent. Between 20
and 40% of UTI episodes are followed by recurrent UTIs (rUTIs), with some women suffering as many as 6 or
more recurrences per year. Uropathogenic Escherichia coli (UPEC) is the major causative agent of UTIs.
Antibiotic resistance within UPEC isolates is rising, and the emergence of extended-spectrum beta-lactamase
producing and fluoroquinolone resistant strains is a serious public health concern. Type 1 pili, tipped with the
mannose binding FimH adhesin have been shown to be essential for bladder colonization and UTI pathogenesis
in multiple mouse models. FimH mediates binding to mannosylated uroplakins lining the bladder surface to
facilitate colonization and invasion into bladder cells where they rapidly replicate into intracellular bacterial
communities that protect UPEC from immune cells and antibiotics. In addition, FimH facilitates the ability of
UPEC to establish a reservoir in the GIT, from where they can seed UTIs by ascending from the periurethral
area into the bladder. While UPEC are genetically variable, FimH is part of the core E. coli genome, although
rare strains have been found with mutations in the type 1 operon. Immunization against FimH protects against
UPEC UTI in murine and monkey cystitis models and a FimH-based vaccine has been allowed by the FDA for
patients suffering from multi-drug resistant UPEC. In animal models, protection is antibody-mediated, as FimH-
specific IgG antibodies are found in the urine from protected animals and can protect from UTI through passive
transfer. Intriguingly, UPEC abundance in the gut is increased at the time of symptomatic UTI, suggesting that
gut colonization is a key step in the rUTI cycle. Additionally, studies in this proposal show that eliciting a mucosal
antibody response against FimH can reduce UPEC colonization of the gut. In light of these findings, this proposal
addresses the hypothesis that anti-FimH induced antibodies can combat rUTI by two distinct mechanisms: i)
prevention of UPEC binding to the uroepithelium; and ii) interference with UPEC colonization of the GIT, thereby
lowering the likelihood of UPEC introduction into the urinary tract. The aims of this proposal are to: i) determine
how mucosal vaccination against FimCH reduces UPEC gut colonization (Aim 1); ii) exploit vaccine induced B
cell responses to isolate monoclonal antibodies (mAbs) to FimH and determine their epitope specificity (Aim 2);
and iii) use these mAbs in mouse models of GIT colonization and cystitis in order to elucidate mechanisms of
protection (Aim 3). The research plan will unravel the mechanisms by which anti-FimH antibodies may function
to prevent UTIs by directly blocking bladder binding and indirectly by interfering with UPEC GIT colonization.
These results will ...

## Key facts

- **NIH application ID:** 10344461
- **Project number:** 1R01AI165915-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Andrew Leon Kau
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $630,335
- **Award type:** 1
- **Project period:** 2021-11-10 → 2026-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10344461

## Citation

> US National Institutes of Health, RePORTER application 10344461, Harnessing Antibody Responses to Prevent and Treat Urinary Tract Infections (1R01AI165915-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10344461. Licensed CC0.

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