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Monkeypox (mpox) is an infectious disease caused by the mpox virus and can potentially lead to fatal outcomes. It resembles infections caused by viruses from other families, challenging identification. The pathogenesis, transmission, and clinical manifestations of mpox and other Orthopoxvirus species are similar due to their closely related genetic material. This review provides a comprehensive discussion of the roles of various proteins, including extracellular enveloped virus (EEV), intracellular mature virus (IMV), and profilin-like proteins of mpox. It also highlights recent diagnostic techniques based on these proteins to detect this infection rapidly.

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. The monkeypox‐specific bionic vaccine (AM@AEvs‐PB) is consists of IMV antigens (A29L, M1R), the EEV antigen (B6R), and MPV‐preactivated macrophagederived vesicles. AM@AEvs‐PB can induce enhanced innate immune responses, promote cross‐presentation of antigens to dendritic cells (DCs), and elicit robust adaptive immune responses, realizing immunization protection against Monkeypox Virus.