Historic smallpox vaccination and Mpox cross-reactive immunity: Evidence from healthcare workers with childhood and adulthood exposures.

In recent years, human mpox has made multiple resurges, prompting public health professionals to consider factors that lead to the increased risk for the reemergence of other orthopoxviruses. Due to the genetic similarity between orthopoxviruses, vaccinia vaccines used to prevent smallpox transmission are also indicated and have been used for mpox infection prevention and control. In this study, cross-reactive immunity for mpox was observed among individuals with self-reported history of smallpox vaccination. Differences in mean antigen response among individuals vaccinated in childhood and adulthood versus individuals vaccinated in childhood only were also observed, supporting the hypothesis that childhood smallpox vaccination may not be sufficient in providing long-lasting protection against multiple orthopoxviruses. These results provide insight on the durability of mpox immunogenic proteins and can be used to inform future studies to assess the benefits of reestablishing vaccinia vaccines as standard recommended immunizations, particularly where orthopoxviruses, such as mpox, are endemic.