A Systematic Review of the Current Evidence of the Effectiveness and Safety of Immunoprophylaxis Using Sublingual Dead Whole Bacteria to Prevent Recurrent Urinary Tract Infections (rUTIs)

<b>Background/Objectives</b>: Recurrent urinary tract infections (rUTIs) remain a major clinical challenge, but sublingual immunoprophylaxis with inactivated whole bacteria is a promising alternative to antibiotic prophylaxis. The objective of this systematic review was to assess the efficacy and safety of sublingual bacterial vaccines. <b>Methods</b>: We searched MEDLINE, Cochrane CENTRAL, and Embase (January 1979-August 2025) for English-language studies evaluating bacterial vaccines for rUTI prevention. Eligible studies included adults receiving sublingual immunoprophylaxis with heat-inactivated whole bacteria. Outcomes were UTI recurrence, infection-free interval, and adverse events. Both MV140 and autovaccines were assessed. <b>Results</b>: Of the 262 records identified, 14 studies met the inclusion criteria (4 comparatives, including 1 randomized trial, and 10 observational studies). UTI incidence decreased from 3.2-6.8 to 0-1.5 episodes/year at 12 months. The proportion of UTI-free patients ranged from 9.8 to 90% with immunoprophylaxis versus 0 to 25% with antibiotics or placebo. At 12 months, UTI-free rates were 10-49% with autovaccines and 9.7-60% with MV140. Patients with ≥3 UTIs ranged from 14.3 to 60.2% and 20 to 56.1% with autovaccines and MV140, respectively. The RCT reported adverse events in 0-40.8% of treated patients and 50% of placebo patients, predominantly mild. <b>Conclusions</b>: Although the available evidence is heterogeneous and largely derived from observational studies, sublingual immunoprophylaxis with heat-inactivated whole-bacteria-either standardized (MV140) or tailored to urine culture results-appears to be an effective and safe strategy for reducing the frequency of rUTI and prolonging infection-free intervals. However, larger randomized trials are required to confirm these findings.