Treatment of Bacterial Infections of the Female Urinary Tract by Immunization of the Patients

Grischke, Eva‐Maria; Rüttgers, H.

doi:10.1159/000281988

Cited by 45 publications

(27 citation statements)

References 2 publications

(2 reference statements)

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“…In humans, leukocyte migration into the bladder wall has been attributed to the CXCL8 chemokine (27)(28)(29)(30)(31). Although much of the initial inflammatory infiltrate is comprised of neutrophils, our study demonstrates that in secondary infections there is recruitment of B and T lymphocytes to the bladder wall.…”

Section: Discussionmentioning

confidence: 76%

Antigen-Specific Responses Accelerate Bacterial Clearance in the Bladder

Thumbikat¹,

Waltenbaugh

Schaeffer³

et al. 2006

The Journal of Immunology

100

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Urinary tract infections (UTIs) cause patient morbidity and have a substantial economic impact. Half of all women will suffer a UTI at least once, and 25% of these women will have recurrent infections. That 75% of previously infected women do not become reinfected strongly suggests a role for an adaptive immune response. The goal of this study was to characterize the adaptive immune responses to uropathogenic Escherichia coli (UPEC), the predominant uropathogen. A novel murine model of UTI reinfection was developed using the prototypic cystitis UPEC isolate NU14 harboring a plasmid encoding OVA as a unique antigenic marker. Bacterial colonization of the bladder was quantified following one or more infections with NU14-OVA. Animals developed anti-OVA serum IgG and IgM titers after the initial infection and marked up-regulation of activation markers on splenic T cells. We observed a 95% reduction in bacterial colonization upon reinfection, and splenic leukocytes showed Ag-specific proliferation in vitro. Adoptive transfer of splenic T cells or passive transfer of serum from previously infected mice protected naive syngeneic mice from UPEC colonization. These findings support our hypothesis that adaptive immune responses to UPEC protect the bladder from reinfection and form the basis of understanding susceptibility to recurrent UTI in women.

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Section: Discussionmentioning

confidence: 76%

Antigen-Specific Responses Accelerate Bacterial Clearance in the Bladder

Thumbikat¹,

Waltenbaugh

Schaeffer³

et al. 2006

The Journal of Immunology

100

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“…Different approaches have been undertaken in this direction (6), but none of them have so far led to a product sufficiently satisfactory for human use. A variety of whole-cell vaccine formulations, administered via vaginal or oral routes, have been assessed in animal models and human clinical trials in Europe (7)(8)(9)(10)(11)(12)(13)(14)(15). These vaccines hold some promise but require further evaluation, particularly in consideration of the fact that whole cell-based vaccines are likely to elicit undesired immune responses against antigens shared with commensal E. coli strains.…”

mentioning

confidence: 99%

Proteomics Characterization of Outer Membrane Vesicles from the Extraintestinal Pathogenic Escherichia coli ΔtolR IHE3034 Mutant

Scorza

Doro

Rodríguez-Ortega

et al. 2008

Molecular & Cellular Proteomics

124

105

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Extraintestinal pathogenic Escherichia coli are the cause of a diverse spectrum of invasive infections in humans and animals, leading to urinary tract infections, meningitis, or septicemia. In this study, we focused our attention on the identification of the outer membrane proteins of the pathogen in consideration of their important biological role and of their use as potential targets for prophylactic and therapeutic interventions. To this aim, we generated a ⌬tolR mutant of the pathogenic IHE3034 strain that spontaneously released a large quantity of outer membrane vesicles in the culture supernatant. The vesicles were analyzed by two-dimensional electrophoresis coupled to mass spectrometry. The analysis led to the identification of 100 proteins, most of which are localized to the outer membrane and periplasmic compartments. Interestingly based on the genome sequences available in the current public database, seven of the identified proteins appear to be specific for pathogenic E. coli and enteric bacteria and therefore are potential targets for vaccine and drug development. Finally we demonstrated that the cytolethal distending toxin, a toxin exclusively produced by pathogenic bacteria, is released in association with the vesicles, supporting the recently proposed role of bacterial vesicles in toxin delivery to host cells. Overall, our data demonstrated that outer membrane vesicles represent an ideal tool to study Gram-negative periplasm and outer membrane compartments and to shed light on new mechanisms of bacterial pathogenesis. Molecular & Cellular Proteomics 7:473-485, 2008.

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“…In a follow-up study, 400 women were randomized to receive parenteral vaccine plus antibiotics as needed or antibiotics alone. The immunized women had fewer reinfections, but 47% had "postvaccinal reactions" including 3.5% with fevers up to 38° C [6]. These adverse reactions were attributed to endotoxin present in the whole-cell preparation.…”

Section: Urovac ®mentioning

confidence: 97%

Vaccine development for the prevention of urinary tract infections

Hopkins

Uehling

2002

Curr Infect Dis Rep

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The effectiveness of antibiotic prophylaxis for recurrent urinary tract infections is being compromised as increasing numbers of uropathogens develop resistance to conventional antibiotics. Because one alternative to antibiotic therapy is immunization of susceptible patients to increase innate resistance, several different vaccines are currently being developed. Four of the vaccines contain a mixture of whole bacteria or an antigenic extract and are administered as a vaginal suppository or oral tablet. A parenteral route is being used in clinical trials of the Escherichia coli type 1 fimbrial adhesin and its chaperone protein. The safety of both the mucosal and parenteral vaccines has been demonstrated in phase 1 clinical trials. Phase 2 trials have shown the efficacy of a vaginal mucosal vaccine containing whole bacteria and an oral vaccine prepared from bacterial lysates. Further clinical trials will allow comparisons of the various vaccines and evaluation of their effectiveness relative to prophylactic antibiotic therapy.

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Treatment of Bacterial Infections of the Female Urinary Tract by Immunization of the Patients

Cited by 45 publications

References 2 publications

Antigen-Specific Responses Accelerate Bacterial Clearance in the Bladder

Antigen-Specific Responses Accelerate Bacterial Clearance in the Bladder

Proteomics Characterization of Outer Membrane Vesicles from the Extraintestinal Pathogenic Escherichia coli ΔtolR IHE3034 Mutant

Vaccine development for the prevention of urinary tract infections

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