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Frequent antibiotic use in urinary tract infections (UTI) is associated with an elevated risk of adverse events as well as developing multidrug resistant UTI. Sublingual vaccination with Uromune® has been shown to reduce the frequency of UTI in patients suffering from recurrent urinary tract infections (rUTI) in the general population. The aim of this study was to describe the clinical and immunological response to this vaccine in kidney transplant recipients with rUTI.Sublingual vaccination with Uromune® was prescribed to kidney transplant patients who met criteria for rUTI (≥2 UTI in the previous 6 months or ≥ 3 UTI in the previous year), administering 2 daily sublingual puffs for 6 months. Patients in the first post-transplant year were excluded. After 1 year of follow-up, the number of UTI episodes and severe episodes requiring hospital admittance were compared to those in the previous year. Changes in renal function and anti-HLA antibodies were measured. Humoral and cellular immune response were monitored by measuring clonal B and T-lymphocyte populations before vaccination and after 3 and 6 months of vaccination.43 kidney transplant recipients with rUTI completed sublingual vaccination with Uromune® for 6 months, age 56.2±15.0 years, median transplant duration 6.0 years (interquartile range (IQR) 3.7-10.5), 86% females, 32.6% had polycystic kidney disease, 32.6% diagnosed with diabetes mellitus, 39.5% had urinary tract structural or functional abnormalities.The mean incidence of UTI decreased from 4.2 to 2.7 episodes per year (CI 95% 0.9-2.2, p<0,001). After one year, 16.3% of patients were completely free from UTI and 46.5% had fewer infections.After 6 months from vaccination, there was an increase in total B lymphocytes from 6.9% (IQR 3.2-13.6) to 8% (IQR 4.4-15.6)(p=0.012), and in memory B cells from 34.3% (IQR 14.1-48.8) to 40.7% (IQR 30.8-54)(p=0.002). There was a decrease in transitional B lymphocytes from 4.7% (IQR 2-9.7) to 1.1% (IQR 0.3-2.5)(p<0.001), in switched memory B cells from 29.6% (IQR 15.6-45) to 14.6% (IQR 7.6-29.3)(p=0.038), and in plasmablasts from 8.6% (IQR 2.1-31.4) to 1.2% (IQR 0.5-3.4)(p=0.009).In vaccine responders, total B lymphocytes increased from 8.6% (IQR 3.7-15.5) to 11.6% (IQR 5.3-16.7)(p=0.005), while plasmablasts decreased from 13% (IQR 2.4-33.1) to 0.75% (IQR 0.3-2.1)(p=0.028) and switched memory B cells from 19.6% (7.3-44.6) to 13.9% (7.2-18). These changes were not found in vaccine non-responders. There were no significant differences in clonal T-cell populations between both groups.No significant changes in serum creatinine or development of new anti-HLA antibodies were found.Sublingual administration of polybacterial vaccine Uromune® can reduce the frequency of UTI in kidney transplant patients with rUTI through the induction of humoral immune response. In our study, no changes in renal function or development of new anti-HLA antibodies were found.