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

Abstract

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 <i>Acinetobacter baumannii</i> elicits rapid protection against broad <i>A. baumannii</i>-infected pneumonia via training of innate immune response in <i>Rag1</i>^-/- 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 <i>Pseudomonas aeruginosa</i> and <i>Klebsiella pneumoniae</i> pneumonia models, but not in <i>Staphylococcus aureus</i> and <i>Streptococcus pneumoniae</i> 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.