Vaccination and Covering Behaviors Against Mpox: Timing, Effectiveness and Robustness

When it comes to the control of mpox, vaccination plays a key role, but there are supply and uptake limiations faced by real world rollout. Lesion covering is a simple, low-cost behavior that could reduce transmission immediately, yet its role has remained underexplored. This study presents a modeling framework that incorporates vaccination throughput, vaccine efficacy, adoption of covering, protection durability, and persistence. Using this framework, we simulated U.S. outbreak patterns under vaccination-only, covering-only, and combined approaches. We assessed the consistency of outcomes across uncertain parameters through global sensitivity analysis and Latin Hypercube sampling. We show that vaccination and covering are not substitutes but synergistic levers. Vaccination alone reduces cumulative cases by 34.2% and yields epidemic control in only 24.3% of simulations. Covering alone contributes almost nothing (-0.2%; 0% chance of control). In contrast, combining both cuts cumulative burden by 80.0% and nearly doubles the probability of suppression (P(R_e<1) rises from 0.243 to 0.476). Persistence matters: when covering rapidly wanes, its impact disappears, but when sustained, it markedly enhances vaccination effectiveness. Global sensitivity analyses reveal four dominant drivers; transmission, recovery, covering protection, and two-dose effectiveness, with behavioral reversion strongly shaping outcomes. Our results demonstrate that lesion covering is best understood not as a standalone solution, but as a force multiplier for vaccination. By extending coverage before vaccines reach scale and by sustaining reductions afterward, covering nearly doubles the likelihood of epidemic control.