Recurrent UTIs: Hope for Vaccine Alternatives Faces Mounting Evidence Challenges
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The search for alternatives to antibiotics in preventing recurrent urinary tract infections (UTIs) is strong, but recent scientific shifts are casting doubt on the effectiveness of currently available immunoactive products.Despite initial promise, the evidence supporting these vaccines remains questionable, leading to fluctuating recommendations from leading medical authorities.
Shifting Recommendations from the European Association of Urology
initial optimism surrounding immunoactive products stemmed from a 2020 meta-analysis that prompted the european Association of Urology (EAU) to consider their effectiveness for preventing recurrent cystitis in women, citing “level 1a evidence.” However, a subsequent 2024 meta-analysis, incorporating more recent data and stricter methodological criteria, has led the EAU to downgrade its recommendation. The 2024 analysis included 21 randomized controlled trials (RCTs) – compared to the 17 studies (12 RCTs) used in the 2020 analysis. Notably, the 2024 meta-analysis excluded several studies from the 1980s due to methodological weaknesses, while incorporating more recent research up to 2023. This resulted in a more moderate assessment of benefit, with a relative risk of 1.52.
Unclear Mechanisms of Action Raise Concerns
Beyond the conflicting clinical data, the essential science behind how these products work remains largely unknown. A recent study conducted by researchers at the Institut Pasteur-Université Paris Cité utilized a mouse model of cystitis. While the study found a reduction in recurrent infections in rodents treated with OM-89 in combination with fosfomycin or trimethoprim-sulfamethoxazole, no benefit was observed with OM-89 alone.
Crucially, the research revealed no important changes in IgA or IgG production in bladder tissue or blood, nor did it demonstrate any protection upon re-exposure to the same bacteria. Furthermore, the bacterial reservoir within the bladder tissue remained unchanged. “These data contradict what is usually put forward,” emphasized an infectious disease specialist, referring to the widely held belief that these products stimulate non-specific IgA and IgG production, bolstering local and systemic immunity. This assertion, the specialist noted, is largely based on a limited experiment involving fewer than ten mice in the 1990s, lacking crucial follow-up data on subsequent urinary infections. Moreover, evidence of IgA production is primarily documented in the intestinal tract, not the urinary tract.
Further proposed mechanisms, such as the activation of antigen-presenting cells, are primarily supported by in vitro experiments.
Positioning Immunoactive Products in Clinical Practice
Given the current state of evidence, experts suggest a cautious approach. One specialist believes these products have a place “between hygiene measures and situations of contraindication or failure of antibiotic prophylaxis,” but stresses the need for rigorous clinical trials with clearly defined criteria for recurrent cystitis.
A Variety of Approaches to Immunoprophylaxis
Several immunoactive prophylactic strategies have been developed, all utilizing Escherichia coli but employing diverse immunomodulatory techniques. These include:
- OM-89 (Uro-Vaxom): An oral formulation consisting of lyophilized lysates from 18 strains of uropathogenic E. coli, administered as one capsule daily for 90 days.
- Solco-Urovac: An intravaginal formulation containing a mixture of heat-killed whole bacteria, administered on days 1, 3, and 5, with optional booster doses.
- MV140 (Uromune): A sublingual spray containing heat-killed whole bacteria, administered as two sprays daily for three months.
- StroVac: An injectable version of Solco-Urovac, delivered via three intramuscular injections spaced two weeks apart.
- ExPEC4V: Currently in clinical trials only,this injectable formulation consists of lipopolysaccharides from E. coli.
Ultimately, solidifying the role of these products in combating urinary infections requires considerably stronger clinical data and a clearer understanding of their underlying mechanisms.
