Enhancing antibacterial immunotherapy for bacterial pneumonia via nanovaccines coated with outer membrane vesicles

Abstract

The increase in drug-resistant microbial infections and the reduction in the number of approvals for new antibiotic categories make engineered biological agents difficult to use in traditional therapies. Here, we reported a nanovaccine encapsulated in the bacterial outer membrane vesicles (OMVs) to enhance the antibacterial immunotherapy of bacterial pneumonia. Using Pseudomonas aeruginosa as a model pathogen, we successfully synthesized the LPS@DMON@OMV nanovaccine using the non-replicable bacterial OMV as the antigen and LPS as the adjuvant. When injected subcutaneously, the vaccine induced rapid activation and maturation of dendritic cells (DCs) in the lymph nodes of immunized mice. The specific antibody titer stimulated by nanovaccine was 180 times higher than that stimulated by free OMV, and it can also stimulate the generation of more toxic T cells to eliminate bacteria in the body. In addition, the nanovaccine can also stimulate the body to form immune memory. The specific antibodies and memory T cells in the body can be retained for up to three months, which can prevent the risk of bacterial infection. These results indicate that the use of natural bacterial membranes to encapsulate synthetic nanoparticles has great prospects in the design of effective antibacterial vaccines.