Vaccine development for the prevention of urinary tract infections

Hopkins, Walter J.; Uehling, David T.

doi:10.1007/s11908-002-0037-8

Cited by 18 publications

(7 citation statements)

References 23 publications

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“…Acute pyelonephritis and bacteremia can also be serious complications of UTI. Indeed, the societal and economic impact of these complications caused by E. coli , combined with increasing antibiotic and multidrug resistance has prompted a demand for a vaccine to prevent UTI in women with a history of recurrent infection [7–9].…”

Section: Introductionmentioning

confidence: 99%

UTI patients have pre-existing antigen-specific antibody titers against UTI vaccine antigens

Sarkissian

Alteri

Mobley

2019

Vaccine

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Urinary tract infection (UTI) is most frequently caused by uropathogenic Escherichia coli (UPEC). Our laboratory has been developing an experimental vaccine targeting four UPEC outer membrane receptors involved in iron acquisition – IreA, FyuA, IutA, and Hma – to elicit protection against UTI. These vaccine targets are all expressed in humans during UTI. In the murine model, high titers of antigen-specific serum IgG or bladder IgA correlate with protection against transurethral challenge with UPEC. Our aim was to measure levels of pre-existing serum antibodies to UTI vaccine antigens in our target population. To accomplish this, we obtained sera from 64 consenting female patients attending a clinic for symptoms of cystitis. As a control, we also collected sera from 20 healthy adult male donors with no history of UTI. Total IgG and antigen-specific IgG titers were measured by ELISA. Of the 64 female patients, 29 had significant bacteriuria (>104 cfu/ml urine) and uropathogenic E. coli (UPEC). Thirty-five patients had non-significant bacteriuria (<104 cfu/ml). Antigen-specific IgG titers did not correlate with the presence or absence of the gene encoding the antigen in the infecting strain (when present), but rather titers were proportional to prevalence of genes encoding antigens among representative collections of UPEC isolates. Surprisingly, we obtained similar results when sera from healthy male patients without history of UTI were tested. Thus, unvaccinated adults have non-protective levels of pre-existing antibodies to UTI vaccine antigens, establishing an important baseline for our target population. This suggests that a UTI vaccine would need to boost pre-existing humoral responses beyond these background levels to protect from infection.

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Section: Introductionmentioning

confidence: 99%

UTI patients have pre-existing antigen-specific antibody titers against UTI vaccine antigens

Sarkissian

Alteri

Mobley

2019

Vaccine

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“…Uro-Vaxom is an oral vaccine, licensed in over 30 countries, which is composed of bacterial crude extracts from eighteen UPEC strains and has been shown in several randomized placebo controlled trials to reduce the frequency of UTI recurrence [ 100 , 101 , 102 , 103 , 104 , 105 ]. Urovac is a vaginal mucosal multivalent vaccine made up of whole inactivated bacteria including six strains of heat inactivated UPEC along with four other strains of uropathogenic bacteria [ 106 , 107 ]. Data reported on three clinical trials demonstrated a reduction of recurrent UTIs during a 6-month period after immunization with Urovac [ 108 ].…”

Section: State Of the Art Of Vaccines And Mabs To Tackle Pseudomonas Aeruginosa And Escherichia Colimentioning

confidence: 99%

Strategies to Tackle Antimicrobial Resistance: The Example of Escherichia coli and Pseudomonas aeruginosa

Antonelli

Cappelli

Cinelli

et al. 2021

IJMS

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Traditional antimicrobial treatments consist of drugs which target different essential functions in pathogens. Nevertheless, bacteria continue to evolve new mechanisms to evade this drug-mediated killing with surprising speed on the deployment of each new drug and antibiotic worldwide, a phenomenon called antimicrobial resistance (AMR). Nowadays, AMR represents a critical health threat, for which new medical interventions are urgently needed. By 2050, it is estimated that the leading cause of death will be through untreatable AMR pathogens. Although antibiotics remain a first-line treatment, non-antibiotic therapies such as prophylactic vaccines and therapeutic monoclonal antibodies (mAbs) are increasingly interesting alternatives to limit the spread of such antibiotic resistant microorganisms. For the discovery of new vaccines and mAbs, the search for effective antigens that are able to raise protective immune responses is a challenging undertaking. In this context, outer membrane vesicles (OMV) represent a promising approach, as they recapitulate the complete antigen repertoire that occurs on the surface of Gram-negative bacteria. In this review, we present Escherichia coli and Pseudomonas aeruginosa as specific examples of key AMR threats caused by Gram-negative bacteria and we discuss the current status of mAbs and vaccine approaches under development as well as how knowledge on OMV could benefit antigen discovery strategies.

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“…48 It remains uncertain which route of administration will be best (parenteral, oral or vaginal) and which patients will benefit most from this exciting development. 49,50 Herbal products have also been proposed as a means of preventing RUTI and have shown promise, but larger sample sizes and confirmatory studies are needed. 51…”

Section: Future Preventative Strategiesmentioning

confidence: 99%

Recurrent urinary tract infections in non-pregnant adult women

Henn

2009

South African Family Practice

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Recurrent urinary tract infections occur in approximately 5% of adult women. It has a significant impact on the affected women's quality of life and on health care costs. It is important to be aware of the physiologically protective factors preventing urinary tract infections. The clinician should also be able to identify relevant risk factors for recurrent infection. Clinical evaluation is relatively straightforward in cases without underlying complicating factors, but urine culture ought to be readily utilised. Treatment should be according to local antibiogram patterns and prophylactic and postcoital preventative strategies can be used according to current evidence. Certain subpopulations such as HIV positive patients require a different approach compared to the general population.Peer reviewed. (

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Vaccine development for the prevention of urinary tract infections

Cited by 18 publications

References 23 publications

UTI patients have pre-existing antigen-specific antibody titers against UTI vaccine antigens

UTI patients have pre-existing antigen-specific antibody titers against UTI vaccine antigens

Strategies to Tackle Antimicrobial Resistance: The Example of Escherichia coli and Pseudomonas aeruginosa

Recurrent urinary tract infections in non-pregnant adult women

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