Urinary tract infections (UTI) remain among the most common bacterial infections and constitute a large public health cost to society. UTI's are caused primarily by E. coli which infect the bladder by an ascending route. Even in patients without demonstrable vesico-ureteral reflux or obstruction, an lower tract UTI may proceed to pyelonephritis. The overall goal of this research continues to be establishment of a safe and effective vaccine treatment against UTI. The current approach of treating women with recurrent UTI is to prevent reinfection by long term administration of low dose antibiotics. However, extended use of antibiotics may cause adverse reactions in patients and the development of antibiotics-resistant uropathogens. An alternative treatment approach is to boost innate resistance to UTI by immunization. In animal models and clinical trials, vaginal mucosal immunization with a multi-strain vaccine can be shown to lessen the severity and duration of experimentally induced UTI's and prolong the time til reinfection in susceptible female patients. This investigation is now focused on prolonging the protective period in susceptible women by giving immunization boosters at the times when protection in our Phase II trial appears to be decreasing. The specific aims of the proposal are: 1. Complete and extended Phase II clinical trial with a multi-strain immunogen given as a vaginal suppository, with additional immunizations timed to provide sustained protection. 2. Utilize an animal model to clarify the immunologic basis for the increased resistance to UTI following vaginal immunization and to evaluate adjuvants and vaccination regimes that optimize immunogenicity and efficacy of UTI vaccines.