Monkey pox (Mpox): pathogenesis, genetic shifts, vaccination strategies and clinical insights

Monkeypox (mpox) is an emerging orthopoxviral disease that has re-emerged globally since 2022, with over 163,000 confirmed cases reported across multiple World Health Organization regions. Mpox has two large clades; Clade I which is mostly related to Central Africa and more severe disease and Clade II which has caused recent multinational outbreaks and is represented by the B.1 lineage. This review is an overview of the existing findings on the pathogenesis of mpox, viral evolution, immune evasion strategies, and the protective efficacy of smallpox and third-generation mpox vaccines based on epidemiological, clinical, immunological, and vaccine-related literature published in leading biomedical databases. Recent evidence suggests that mpox has several immune evasion mechanisms that interrupt innate and cellular immune responses, allowing prolonged human-to-human infection. High risks populations are disproportionately affected by the disease especially men who have sex with men and people living with HIV who become more susceptible, and severity of the disease worsens. Previous smallpox vaccination offers a significant level of cross-protective immunity, with aggregate evidence indicating that it offers protection of about 80 percent and a considerably lower risk of becoming infected. Third-generation vaccines such as MVA-BN/JYNNEOS, are showing good safety profiles, moderate to high efficacy in comparison to older vaccines like the ACAM2000, with other platforms being under clinical development. Knowledge of clade-specific viral evolution, immune resistance and vaccine efficacy is crucial to the optimization of vaccination response, the prioritization of susceptible population, and preparedness to future outbreaks of ortho poxvirus.