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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK030808-17
Application #
6329305
Study Section
Special Emphasis Panel (ZRG4-UROL (01))
Program Officer
Nyberg, Leroy M
Project Start
1982-04-01
Project End
2002-11-30
Budget Start
2000-12-01
Budget End
2002-11-30
Support Year
17
Fiscal Year
2001
Total Cost
$251,651
Indirect Cost
Name
University of Wisconsin Madison
Department
Surgery
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Hopkins, Walter J; Elkahwaji, Johny; Beierle, Lori M et al. (2007) Vaginal mucosal vaccine for recurrent urinary tract infections in women: results of a phase 2 clinical trial. J Urol 177:1349-53;quiz 1591
Uehling, David T; Hopkins, Walter J; Elkahwaji, Johny E et al. (2003) Phase 2 clinical trial of a vaginal mucosal vaccine for urinary tract infections. J Urol 170:867-9
Morin, Michelle D; Hopkins, Walter J (2002) Identification of virulence genes in uropathogenic Escherichia coli by multiplex polymerase chain reaction and their association with infectivity in mice. Urology 60:537-41
Uehling, D T; Hopkins, W J; Beierle, L M et al. (2001) Vaginal mucosal immunization for recurrent urinary tract infection: extended phase II clinical trial. J Infect Dis 183 Suppl 1:S81-3
Jones-Carson, J; Balish, E; Uehling, D T (1999) Susceptibility of immunodeficient gene-knockout mice to urinary tract infection. J Urol 161:338-41
Hopkins, W J; Heisey, D M; Uehling, D T (1999) Association of human leucocyte antigen phenotype with vaccine efficacy in patients receiving vaginal mucosal immunization for recurrent urinary tract infection. Vaccine 17:169-71
Hopkins, W J; Uehling, D T; Wargowski, D S (1999) Evaluation of a familial predisposition to recurrent urinary tract infections in women. Am J Med Genet 83:422-4
Hopkins, W J; Heisey, D M; Lorentzen, D F et al. (1998) A comparative study of major histocompatibility complex and red blood cell antigen phenotypes as risk factors for recurrent urinary tract infections in women. J Infect Dis 177:1296-301
Uehling, D T; Hopkins, W J; Balish, E et al. (1997) Vaginal mucosal immunization for recurrent urinary tract infection: phase II clinical trial. J Urol 157:2049-52
Hopkins, W; Gendron-Fitzpatrick, A; McCarthy, D O et al. (1996) Lipopolysaccharide-responder and nonresponder C3H mouse strains are equally susceptible to an induced Escherichia coli urinary tract infection. Infect Immun 64:1369-72

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