Single-dose of hybrid eukaryotic-prokaryotic nanovesicles to drive a rapid and controllable immune response against Klebsiella pneumoniae induced nosocomial pneumonia

Klebsiella pneumoniae is the main pathogen of hospital-acquired infections causing acute pneumonia, which is characterized by drug resistance, virulence and mortality, and for which there is no clinically approved vaccine formulations. Here, we designed biomimetic hybrid membrane vesicles (HMVs), which consist of outer membrane vesicles of Klebsiella pneumoniae and cell membrane vesicles of alveolar macrophages. The HMVs were administered via intratracheal instillation to mimic the delivery of an inhaled formulation, where immune cells could be rapidly mobilized in the lungs to promote pathogen-specific immunity and to establish local mucosal immunity. In a mouse model of acute pneumonia with experimental strain 43,816 and clinical strain 7,29,088, immunization of HMVs via the lungs provided significant protection, reduced the number of colonies in deep tissues, improved survival, and reduced symptoms of acute inflammation. As expected, HMVs not only retained the immunogenicity of OMVs, but also effectively reduced the excessive immune response induced by OMVs. In conclusion, as a proof-of-concept for the design of antibacterial vaccines, the HMVs is an effective platform for activating bacteria-specific immunity, which can rapidly and effectively protect against nosocomial pneumonia caused by Klebsiella pneumoniae.