Background: Respiratory infections are the most common and potentially most severe type of infections. Antibiotics are the mainstay treatment, despite many of them being of viral aetiology. Antibiotic overuse and misuse are posing a global threat due to the generation of multidrug resistance. Thus, the development of alternative strategies has become a priority. Aim: MV130 falls within the new concept of mucosal Trained Immunity-based Vaccine (TIbV). It is composed of heat-inactivated whole-cell bacteria and has been shown to confer heterologous protections against a broad range of pathogens, including viruses and bacteria, through trained immunity. We hypothesised that MV130 could reduce the number of recurrent respiratory tract infections (RRTIs) and, therefore, antibiotic consumption in children suffering from RRTIs. Methods: A retrospective multicentre study including 186 children from 6 months to 17 years of age suffering from RRTIs was conducted. The number of infectious episodes and antibiotic courses 12 months prior and 12 months following MV130 sublingual immunisation was assessed. Results: MV130 significantly reduced the number of infections both in the upper (from a median of 5.0 [interquartile range (IQR), 4.0-6.0] to 1.0 [IQR, 0.0-2.0]), and the lower (from a median of 5.0 [IQR, 4.0-6.0] to 2.0 [IQR, 1.0-3.0]) airways (p<0.0001). Infectious episodes decreased more than 50% in all the assessed aged groups.  Antibiotic consumption was also significantly reduced from a median of 4.0 (IQR, 3.0-5.0) to 0.0 (IQR, 0.0-1.0) courses (p<0.0001). Conclusion: MV130 is an effective strategy in the prevention of RRTIs and the reduction of antibiotic uptake in children.