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Background: Recurrent urinary tract infection (rUTI) remains a major health burden for women. A randomized, double-blind, placebo-controlled trial (RCT; NCT02543827) reported that female patients with rUTI receiving a sublingual vaccine, MV140, had a reduction in rUTI and increase in UTI-free rate compared with placebo. Objective: To determine the impact of MV140 on the personal burden of disease in women with rUTI using secondary endpoint data from the pivotal RCT evaluating MV140. Design, setting, and participants: In the primary RCT, female patients with rUTI enrolled in Spain and UK (from October 2015 to April 2019) were randomized to placebo (6 mo) or MV140 (3 or 6 mo), and followed for 12 mo. Individuals analyzed in this secondary analysis included those in the placebo and 3-mo (recommended dose) groups. Intervention: A polybacterial sublingual vaccine, MV140 (four inactivated whole-cell bacteria—Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, and Enterococcus faecalis), or placebo. Outcome measurements and statistical analysis: Symptom severity scoring, antibiotic use, safety, and multiple aspects of quality of life (QoL; Short-Form Questionnaire [SF-36]) were assessed. Results and limitations: Compared with the placebo group (n = 76), the 3-mo vaccinated group (n = 74) experienced fewer overall UTI symptoms (mean symptom score 102.2 ± 222.9 vs 194.2 ± 178.8; p = 0.0002), fewer days on antibiotics (12.4 ± 17.7 vs 28.7 ± 25.2; p = 0.0001), and improved total, general, and physical SF-36 QoL improvement (differences in means for total SF-36 score 15.7; 95% confidence interval [CI] 8.80, 22.64; p

BackgroundPolymerized allergoids conjugated with mannan represent a novel approach of allergen immunotherapy targeting dendritic cells. In this study, we aimed to determine the optimal dose of mannan-allergoid conjugates derived from grass pollen (Phleum pratense and Dactylis glomerata) administered via either the subcutaneous or sublingual route.MethodsA randomized, double-blind, placebo-controlled trial with a double-dummy design was conducted, involving 162 participants across 12 centers in Spain. Subjects were randomly allocated to one of nine different treatment groups, each receiving either placebo or active treatment at doses of 500, 1,000, 3,000, or 5,000 mTU/mL over four months. Each participant received five subcutaneous (SC) doses of 0.5 mL each, every 30 days, and a daily sublingual (SL) dose of 0.2 mL. Participants who received active treatment through SC, received placebo through SL. Participants who received active treatment through SL, received placebo SC. One Group, as control, received bot SC and SL placebo. The primary efficacy outcome was the improvement in titrated nasal provocation tests (NPT) at the end of the study compared to baseline. Secondary outcomes included specific antibody (IgG4, IgE) and cellular (IL-10 producing and regulatory T cell) responses. All adverse events and side reactions were recorded and assessed.ResultsPost-treatment, the active groups showed improvements in NPT ranging from 33% to 53%, with the highest doses showing the greatest improvements regardless of the administration route. In comparison, the placebo group showed a 12% improvement. Significant differences over placebo were observed at doses of 3,000 mTU/mL (p=0.049 for SL, p=0.015 for SC) and 5,000 mTU/mL (p=0.011 for SL, p=0.015 for SC). A dose-dependent increase in IgG4 was observed following SC administration, and an increase in IL-10 producing cells for both routes of administration. No serious systemic or local adverse reactions were recorded, and no adrenaline was required.ConclusionGrass pollen immunotherapy with mannan-allergoid conjugates was found to be safe and efficacious in achieving the primary outcome, whether administered via the subcutaneous or sublingual routes, at doses of 3,000 and 5,000 mTU/mL.Clinical trial registrationhttps://www.clinicaltrialsregister.eu/ctr-search (EudraCT), identifier 2014–005471–88; https://www.clinicaltrials.gov, identifier NCT02654223.

Respiratory tract infections (RTIs) are among the most common and important problems in clinical medicine, making antibiotics the gold standard therapeutic option regardless of their frequent viral etiology. Their excessive and inappropriate use contributes to the rapid rise of antibiotic resistance and underscores the need for alternative strategies, especially when dealing with recurrent RTIs. Prevention is the ideal alternative, but specific vaccines targeting a wide range of respiratory pathogens are scarce. MV130 is a sublingual bacterial vaccine that induces trained immunity and provides non-specific protection against respiratory pathogens in various clinical settings according to the concept of TIbV (Trained Immunity-based Vaccine). A retrospective real-world study (RWS) was conducted to evaluate the annual incidence of RTIs and the consumption of antibiotics before and after the administration of MV130, using data sourced from the medical records of 599 patients (186 children and 413 adults) who suffered from recurrent RTIs. The median number of infectious episodes in children was significantly reduced by more than 70% from 5 episodes (interquartile range (IQR) 4.0–6.0) to 1 (IQR, 0.0–2.0) (p < 0.001) after MV130. Similarly, in adults, the median number of episodes before MV130 immunization was 5 (IQR, 4.0–6.0), which dropped by more than 80% to 1 (IQR, 0.0–1.0) during the year following MV130 immunization (p < 0.001). The median number of antibiotic courses also significantly decreased for both children and adults by over 80% (p < 0.001). This RWS showed that MV130 is an effective strategy for the prevention of respiratory infections and the reduction of associated antibiotic consumption.