Background: Respiratory tract infections are among the most frequent causes of illness worldwide. Antibiotics are the mainstay of therapy for infections, despite many of these being of viral origin. Antibiotic abuse has led to an unstoppable growth of multidrug resistance. New strategies are urgently needed to provide an effective and safe alternative for management of recurrent respiratory tract infections (RRTIs). Aim: To evaluate the clinical impact of mucosal MV130 administration in reducing both the number of infectious episodes and antibiotic intake in adults with RRTI. MV130 is a Trained Immunity-based Vaccine (TIbV), a new concept of vaccines, that consists of a suspension of inactivated whole-cell bacteria, which prevents RRTIs from diverse aetiology, inducing trained immunity. Methods: A retrospective multicenter study was carried out in a cohort of 413 adults suffering from RRTIs. Subjects were sublingually administered with MV130 and evaluated for their infectious episodes and antibiotic courses 12 months prior and 12 months following immunisation. Results: MV130 significantly reduced the number of RRTIs, both upper respiratory tract infections (URTIs) from a median of 5.0 [interquartile range (IQR), 4.0-6.0] to 1.0 [IQR, 0.0-1.0], and lower respiratory tract infections (LRTIs), from a median of 4.0 [IQR, 3.0-5.0] to 1.0 [IQR, 0.0-2.0], by more than 50% (p<0.0001). Antibiotic consumption was also significantly reduced from a median of 4 [IQR, 3.0-5.0] to 0.0 [IQR, 0.0-1.0] courses in URTIs, and 3 [IQR, 3.0-4.0] to 1.0 [IQR, 0.0-1.0] courses in LRTIs (p<0.0001). Conclusion: MV130 is a potential tool for RRTI prevention and antibiotic cut down in adults.