Abstract
The emergence of monkeypox has become a global health threat after the COVID-19 pandemic. Due to the lack of available specifically treatment against MPV, developing an available vaccine is thus the most prospective and urgent strategy. Herein, a programmable macrophage vesicle based bionic self-adjuvanting vaccine (AM@AEvs-PB) is first developed for defending against monkeypox virus (MPV). Based on MPV-related antigen-stimulated macrophage-derived vesicles, the nanovaccine is constructed by loading the mature virion (MV)-related intracellular protein (A29L/M1R) and simultaneously modifying with the enveloped virion (EV) antigen (B6R), enabling them to effectively promote antigen presentation and enhance adaptive immune through self-adjuvant strategy. Owing to the synergistic properties of bionic vaccine coloaded MV and EV protein in defensing MPV, the activation ratio of antigen-presenting cells is nearly four times than that of single antigen in the same dose, resulting in stronger immunity in host. Notably, intramuscular injection uptake of AM@AEvs-PB demonstrated vigorous immune-protective effects in the mouse challenge attempt, offering a promising strategy for pre-clinical monkeypox vaccine development.