Global Transmission, Prevention, Control, and Treatment of Mpox Virus in 2025: A Comprehensive Review from Infection Mechanisms to Vaccine Development.

The World Health Organization (WHO) declared the mpox (MPX) outbreak a public health emergency of international concern (PHEIC) on 23 July 2022, and 14 August 2024, respectively, underscoring the confirmed and concerning global spread of the disease. A gap exists in our fundamental understanding of the mpox virus (MPXV), despite its genetic relatedness to the variola virus (VARV). This knowledge deficit is evident in the performance of current medical countermeasures; vaccines and antiviral therapies adapted from smallpox programs demonstrate only partial efficacy and are constrained by issues of safety and suboptimal effectiveness against MPXV. In this context, the development of MPX-specific vaccines and antiviral drugs has become a critical priority in the global effort to combat MPX. However, MPXV employs multiple strategies to evade host immune responses, such as producing specific and poxvirus homologous proteins that suppress both innate immunity (including the six principal innate immune signaling pathways and antiviral strategies, notably the interferon [IFN] pathway) and adaptive immunity, thereby complicating vaccine and drug development. Insights from research on vaccinia virus (VACV) and VARV may inform the investigation of MPXV pathogenesis and immune evasion mechanisms. Drawing on relevant scientific literature, this review systematically examines key aspects of MPX infection, pathogenicity, and immune evasion, as well as the coordination between innate and adaptive immune responses. Furthermore, this review elucidates the current application and deployment landscape of the three principal therapeutics and three major vaccines for MPX, aiming to provide a theoretical foundation for future research and development of vaccines and targeted antiviral agents.