Trained immunity-based mucosal immunotherapies for the prevention of respiratory infections

The devastating impact of respiratory infections demonstrates the critical need for novel prophylactic vaccines. In this opinion article, we advocate for bacterial immunotherapies as a complementary tool in our fight against respiratory infections. These immunotherapies can activate a wide spectrum of immunological mechanisms, with trained immunity (TI) being particularly significant. This phenomenon has led to the concept of trained immunity-based vaccines (TIbVs), which represent a novel approach in vaccinology. We discuss examples of TIbVs, including the tuberculosis vaccine Bacille Calmette-Guérin (BCG) and the polybacterial immunotherapy MV130. From our viewpoint, illustrating the mode of action and clinical evidence supports the proposal that TIbVs should be considered as next-generation vaccines to confer protection against a wide range of respiratory infections.