# Vaccine to prevent E. coli urinary tract infection

> **NIH NIH R56** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $423,058

## Abstract

Currently, there is no licensed vaccine to protect humans against urinary tract infection (UTI) in the U.S. Indeed,
UTI is the second most common infection in humans after those of the respiratory tract. This high frequency of
infection results not only in huge annual economic costs, but in decreased workforce productivity and high patient
morbidity. At least 80% of these infections are caused by uropathogenic Escherichia coli (UPEC). Antibiotic
treatment is generally effective for eradication of the infecting strain. However, increasing antibiotic
resistance, allergic reaction to certain pharmaceuticals, alteration of normal gut flora, and failure to prevent
recurrent infections, represent significant barriers to treatment. Our long-term research goal is to develop
approaches to prevent UTI by vaccination, which represents a gap that must be addressed. Our objective is to
strengthen antigen combinations to include siderophores and novel adjuvants for inclusion in an effective
intranasal UTI vaccine. In the current funding period, we determined that intranasal immunization with two UPEC
antigens, Hma and IutA, using dmLT [double mutant of E. coli heat-labile toxin: (R192G/L211A)] as adjuvant,
reduces bladder bacterial load following challenge with UPEC. Our central hypothesis states that a multi-subunit
vaccine elicits an immune response that protects against experimental challenge with UPEC strains. Working
toward a more effective vaccine, we have identified additional protective antigens, siderophore receptor FyuA
and two siderophores, yersiniabactin and aerobactin that also target UPEC. LTA1 has also been identified as an
effective novel adjuvant. Although many women experience recurrent UTI and UPEC heterogeneity complicates
vaccine design, data from our animal model and human studies offer encouragement for successful UPEC
vaccine development. The rationale for the proposed work is to protect women from the development of recurrent
UTI by simple administration of a vaccine. We will test our central hypothesis and complete our objectives by
carrying out two specific aims: 1) Combine protective antigens Hma and IutA with FyuA and siderophores and
novel adjuvants to establish an effective intranasal multi-subunit vaccine for prevention of recurrent urinary tract
infection; and 2) Identify the mechanism of protection for the optimized vaccine against uropathogenic E. coli in
urinary tract infection. For specific aim 1, we will build on our determination that an intranasal vaccine containing
iron acquisition proteins Hma and IutA can protect mice from UTI by UPEC when delivered intranasally with a
mucosal adjuvant. For specific aim 2, we will conduct specific immunological and physiological experiments to
determine how the host is protected from UPEC infection by vaccination. The proposed research is innovative
because we propose to combine discovery of two protective antigens with siderophores and novel adjuvant to
protect against UTI by UPEC. T...

## Key facts

- **NIH application ID:** 10464436
- **Project number:** 2R56AI116791-06A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** HARRY L. MOBLEY
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $423,058
- **Award type:** 2
- **Project period:** 2015-12-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464436

## Citation

> US National Institutes of Health, RePORTER application 10464436, Vaccine to prevent E. coli urinary tract infection (2R56AI116791-06A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10464436. Licensed CC0.

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