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Vaccination strategies for rapid protection against multidrug-resistant bacterial infection are very important, especially for hospitalized patients who have high risk of exposure to these bacteria. However, few such vaccination strategies exist due to a shortage of knowledge supporting their rapid effect. Here, we demonstrated that a single intranasal immunization of inactivated whole cell of  Acinetobacter baumannii  elicits rapid protection against broad  A. baumannii -infected pneumonia via training of innate immune response in  Rag1  -/-  mice. Immunization-trained alveolar macrophages (AMs) showed enhanced TNF-α production upon restimulation. Adoptive transfer of immunization-trained AMs into naive mice mediated rapid protection against infection. Elevated TLR4 expression on vaccination-trained AMs contributed to rapid protection. Moreover, immunization-induced rapid protection was also seen in  Pseudomonas aeruginosa  and  Klebsiella pneumoniae  pneumonia models, but not in  Staphylococcus aureus  and  Streptococcus pneumoniae  model. Our data reveal that a single intranasal immunization induces rapid and efficient protection against certain Gram-negative bacterial pneumonia via training AMs response, which highlights the importance and the possibility of harnessing trained immunity of AMs to design rapid-effecting vaccine.

Vaccination induces rapid protection against bacterial pneumonia via training alveolar macrophage in mice