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. 2004 Apr;171(4):1682-5.
doi: 10.1097/01.ju.0000116123.05160.43.

Antibody responses and protection from pyelonephritis following vaccination with purified Escherichia coli PapDG protein

James A Roberts  1 , M Bernice Kaack, Gary Baskin, Matthew R Chapman, David A Hunstad, Jerome S Pinkner, Scott J Hultgren
Affiliations

Antibody responses and protection from pyelonephritis following vaccination with purified Escherichia coli PapDG protein

James A Roberts et al. J Urol. 2004 Apr.

Abstract

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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Figures

Fig. 1
Fig. 1
Unimmunized monkeys showed antibodies to PapDG and to whole P fimbriae after native E. coli infection. A, serum antipapDG titers before and 3 weeks following urethral infection with 108 cfu DS17 E. coli on ELISA. B, serum antiP fimbriae titers before and 3 weeks following same infection.
Fig. 2
Fig. 2
Five of 6 vaccinated monkeys demonstrated increases in antiPapDG titer after 3 monthly booster doses of PapDG vaccine. IP, intraperitoneal.
See this image and copyright information in PMC

Comment in

References

    1. Vaisanen V, Elo J, Tallgren LG, Siitonen A, Makela PH, Svanborg-Eden C, et al. Mannose-resistant haemagglutination and P antigen recognition are characteristic of Escherichia coli causing primary pyelonephritis. Lancet. 1981;2:1366. - PubMed
    1. Svanborg Eden C, Hagberg L, Leffler H, Lomberg H. Recent progress in the understanding of the role of bacterial adhesion in the pathogenesis of urinary tract infection. Infection. 1982;10:327. - PubMed
    1. Korhonen TK, Virkola R, Westurlund B, Holthofer H, Parkkinen J. Tissue tropism of Escherichia coli adhesins in human extraintestinal infections. Curr Top Microbiol Immunol. 1990;151:115. - PubMed
    1. Otto G, Sandberg T, Marklund BI, Ulleryd P, Svanborg C. Virulence factors and pap genotype in Escherichia coli isolates from women with acute pyelonephritis, with or without bacteremia. Clin Infect Dis. 1993;17:448. - PubMed
    1. Roberts JA, Marklund BI, Ilver D, Haslam D, Kaack MB, Baskin G, et al. The Gal(alpha1–4)Gal-specific tip adhesin of Escherichia coli P-fimbriae is needed for pyelonephritis to occur in the normal urinary tract. Proc Natl Acad Sci USA. 1994;91:11889. - PMC - PubMed

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