PURPOSE: A critical early step in the establishment of Escherichia coli pyelonephritis is bacterial attachment via the tip protein of P fimbriae. This adhesin, PapG, binds to glycolipid receptors present on vaginal and kidney epithelial surfaces. In this study we investigated the efficacy of vaccination with purified PapDG protein complex in preventing pyelonephritis caused by E. coli. MATERIALS AND METHODS: Mature cynomolgus monkeys were intraperitoneally vaccinated with 100 microg purified PapDG protein. Following 3 identical boosters serum antibody titers to PapDG were measured by enzyme-linked immunosorbent assay. Vaccinated and unvaccinated animals were urethrally inoculated with 1 x 10 cfu of E. coli strain DS17, which was isolated from a child with acute pyelonephritis. The infection course was monitored by catheterized urine cultures, and by histological examination of the kidneys, bladder and kidney tissue culture 28 days after infection. RESULTS: Intraperitoneal administration of purified PapDG vaccine resulted in the development of specific antibody responses in cynomolgus monkeys. In contrast to control monkeys, vaccinated monkeys did not show histological evidence of pyelonephritis after subsequent urethral challenge with pyelonephritogenic E. coli expressing P fimbriae. CONCLUSIONS: Purified PapDG is a tractable vaccine candidate that in our small study demonstrated the ability to elicit adequate serum antibody levels to prevent E. coli mediated pyelonephritis.
PURPOSE: A critical early step in the establishment of Escherichia coli pyelonephritis is bacterial attachment via the tip protein of P fimbriae. This adhesin, PapG, binds to glycolipid receptors present on vaginal and kidney epithelial surfaces. In this study we investigated the efficacy of vaccination with purified PapDG protein complex in preventing pyelonephritis caused by E. coli. MATERIALS AND METHODS: Mature cynomolgus monkeys were intraperitoneally vaccinated with 100 microg purified PapDG protein. Following 3 identical boosters serum antibody titers to PapDG were measured by enzyme-linked immunosorbent assay. Vaccinated and unvaccinated animals were urethrally inoculated with 1 x 10 cfu of E. coli strain DS17, which was isolated from a child with acute pyelonephritis. The infection course was monitored by catheterized urine cultures, and by histological examination of the kidneys, bladder and kidney tissue culture 28 days after infection. RESULTS: Intraperitoneal administration of purified PapDG vaccine resulted in the development of specific antibody responses in cynomolgus monkeys. In contrast to control monkeys, vaccinated monkeys did not show histological evidence of pyelonephritis after subsequent urethral challenge with pyelonephritogenic E. coli expressing P fimbriae. CONCLUSIONS: Purified PapDG is a tractable vaccine candidate that in our small study demonstrated the ability to elicit adequate serum antibody levels to prevent E. coli mediated pyelonephritis.
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