Biomimetic Nanomedicine-Triggered <i>in Situ</i> Vaccination for Innate and Adaptive Immunity Activations for Bacterial Osteomyelitis Treatment.

The development of bacterial vaccines for inducing an immunoresponse against infectious diseases such as osteomyelitis is of great significance and importance. However, the responsiveness of bacterial immunotherapy remains far from being satisfactory, largely due to the erratic antigen epitopes of bacteria. Herein, we report an <i>in situ</i> vaccination strategy for the immunotherapy of bacterial infection based on an osteomyelitis model using a biomimetic nanomedicine named as HMMP, which was constructed by engineering PpIX-encapsulated hollow MnO_<i>x</i> with a hybrid membrane exfoliated from both macrophage and tumor cell lines. The as-established HMMP features a burst bacterial antigen release as the <i>in situ</i> vaccine by the augmented sonodynamic treatment and the resultant priming of antigen-presenting cells for the following activations of both cellular and humoral adaptive immunities against bacterial infections. This treatment regimen not only triggers initial bacterial regression in the established osteomyelitis model but also simultaneously generates robust systemic antibacterial immunity against poorly immunogenic secondary osteomyelitis in the contralateral knee and additionally confers long-lasting bacteria-specific immune memory responses to prevent infection relapse. Thus, our study provides a proof of concept of <i>in situ</i> vaccination for the activation of both innate and adaptive antibacterial immune responses, providing an individual-independent bacterial immunotherapy.