The study by Berry et al. investigates the effectiveness of the Modified Vaccinia Ankara (MVA-BN) vaccine against monkeypox (mpox) during the 2022 global outbreak. The vaccine was approved based on its immunogenicity and effectiveness in animal models, but no validated correlate of protection has been identified. The authors performed a systematic search and meta-analysis to determine if vaccinia-binding ELISA endpoint titers can predict vaccine effectiveness against mpox. They found a significant correlation between vaccine effectiveness and vaccinia-binding antibody titers, suggesting that antibody levels may be a correlate of protection. Combining this data with antibody kinetics analysis, they predict the durability of protection and the impact of dose spacing. Delaying the second dose of MVA-BN vaccination was found to provide more durable protection, which is beneficial in outbreaks with limited vaccine stock. The study provides a quantitative evidence-based approach to using antibody measurements to predict the effectiveness of mpox vaccination. The results support the use of MVA-BN as a third-generation smallpox and mpox vaccine, with one dose being non-inferior to historical first-generation smallpox vaccination. The analysis also highlights the importance of optimizing vaccine distribution and dosing intervals to maximize both short-term and long-term protection.The study by Berry et al. investigates the effectiveness of the Modified Vaccinia Ankara (MVA-BN) vaccine against monkeypox (mpox) during the 2022 global outbreak. The vaccine was approved based on its immunogenicity and effectiveness in animal models, but no validated correlate of protection has been identified. The authors performed a systematic search and meta-analysis to determine if vaccinia-binding ELISA endpoint titers can predict vaccine effectiveness against mpox. They found a significant correlation between vaccine effectiveness and vaccinia-binding antibody titers, suggesting that antibody levels may be a correlate of protection. Combining this data with antibody kinetics analysis, they predict the durability of protection and the impact of dose spacing. Delaying the second dose of MVA-BN vaccination was found to provide more durable protection, which is beneficial in outbreaks with limited vaccine stock. The study provides a quantitative evidence-based approach to using antibody measurements to predict the effectiveness of mpox vaccination. The results support the use of MVA-BN as a third-generation smallpox and mpox vaccine, with one dose being non-inferior to historical first-generation smallpox vaccination. The analysis also highlights the importance of optimizing vaccine distribution and dosing intervals to maximize both short-term and long-term protection.