Urinary tract infection (UTI) is the second most common
infection in humans after those involving the respiratory tract. This results not only in huge annual economic costs, but in decreased workforce productivity and high patient morbidity. Most
infections are caused by uropathogenic Escherichia coli (UPEC).
Antibiotic treatment is generally effective for eradication of the infecting strain; however, documentation of increasing antibiotic resistance,
allergic reaction to certain pharmaceuticals, alteration of normal gut flora, and failure to prevent
recurrent infections represent significant barriers to treatment. As a result, approaches to prevent UTI such as vaccination represent a gap that must be addressed. Our laboratory has made progress toward development of a preventive
vaccine against UPEC. The long-term research goal is to prevent UTIs in women with recurrent UTIs. Our objective has been to identify the optimal combination of protective
antigens for inclusion in an effective UTI
vaccine, optimal adjuvant, optimal dose, and optimal route of delivery. We hypothesized that a multi-
subunit vaccine elicits antibody that protects against experimental challenge with UPEC strains. We have systematically identified four
antigens that can individually protect experimentally infected mice from colonization of the bladder and/or kidneys by UPEC when administered intranasally with
cholera toxin (CT) as an adjuvant. To advance the
vaccine for utility in humans, we will group the individual
antigens, all associated with
iron acquisition (IreA, Hma, IutA, FyuA), into an effective combination to establish a multi-
subunit vaccine. We demonstrated for all four
vaccine antigens that
antigen-specific serum
IgG represents a strong correlate of protection in vaccinated mice. High antibody titers correlate with low colony forming units (CFUs) of UPEC following transurethral challenge of vaccinated mice. However, the contribution of cell-mediated immunity cannot be ruled out and must be investigated experimentally. We have demonstrated that
antibodies bind to the surface of UPEC expressing the
antigens. Sera from women with and without histories of UTI have been tested for antibody levels to
vaccine antigens. Our results validate
iron acquisition as a target for vaccination against UTI.