Global health security and smallpox: A strategic review of post-eradication biosafety and preparedness

Abstract The global biosecurity framework faces a potential critical transition driven by synthetic biology advancements and declining population-level immunity. This review evaluates smallpox as a central case study for contemporary pathogen governance and biopolitical preparedness. We analyze the convergence of two primary risks: the technical feasibility of de novo orthopoxvirus synthesis and the expanding immunity gap following the cessation of routine vaccination. The 2022 mpox resurgence is assessed as a sentinel event revealing strategic vulnerabilities in cross-protective immunity. Ultimately, this perspective argues that smallpox reemergence risk is not merely a technological byproduct, but a fundamental global governance crisis. To mitigate these threats, we propose a multidimensional framework integrated with One Health principles and transnational coordination. Maintaining strategic vigilance and institutional memory is presented as a critical political capacity for post-eradication health security.