This study investigates the effectiveness of the Modified Vaccinia Ankara (MVA-BN) vaccine against mpox, using a systematic review and meta-analysis of available data. The MVA-BN vaccine, developed by Bavarian Nordic, was approved for mpox based on immunogenicity and animal model data, not clinical efficacy. The study aimed to determine whether vaccinia-binding ELISA endpoint titer is predictive of vaccine effectiveness against mpox. A significant correlation was found between vaccine effectiveness and vaccinia-binding antibody titers, suggesting that antibody levels may be a correlate of protection. Combining this data with analysis of antibody kinetics after vaccination, the study predicts 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, potentially optimal in outbreaks with limited vaccine stock. Mpox, caused by the monkeypox virus, is endemic in West Africa with significant outbreaks occurring in the 1980s and 1990s. Since 2017, there has been a resurgence of mpox in Nigeria, the Democratic Republic of the Congo, and other parts of Africa, attributed to waning immunity from smallpox vaccines and accumulation of unvaccinated cohorts. In 2022, a global outbreak of mpox resulted in over 91,000 confirmed cases in 115 countries, leading to renewed focus on vaccination as a preventative measure. Although there is no mpox-specific vaccine, first-generation smallpox vaccination was observed to protect individuals against mpox infection during the 1980–1986 outbreak in the DRC, with an estimated vaccine effectiveness of approximately 85%. However, live-replicating vaccinia vaccines have significant risks of serious adverse events, leading to the development of the third-generation MVA-BN vaccine. MVA-BN was approved by the FDA for use as a smallpox and mpox vaccine, with two doses of 1×10⁸ TCID via subcutaneous injection. Regulatory approval was based on demonstrated non-inferior immunogenicity profile and improved safety compared to the second-generation ACAM2000 vaccine. The study found that one dose of MVA-BN provided similar effectiveness to historic vaccination, while two doses provided higher effectiveness. A significant benefit of two-dose vaccination over one-dose vaccination was observed. The study also found that vaccinia-binding titers are a correlate of vaccine effectiveness, with higher titers associated with higher effectiveness. The study predicts that delaying the second dose of MVA-BN vaccination provides more durable protection and may be optimal in outbreaks with limited vaccine stock. The study also predicts that vaccine effectiveness remains high for up to 10 years after a single dose, consistent with reports of long-term protection from first- and second-generation vaccines. The study highlights the importance of understanding mpox vaccination andThis study investigates the effectiveness of the Modified Vaccinia Ankara (MVA-BN) vaccine against mpox, using a systematic review and meta-analysis of available data. The MVA-BN vaccine, developed by Bavarian Nordic, was approved for mpox based on immunogenicity and animal model data, not clinical efficacy. The study aimed to determine whether vaccinia-binding ELISA endpoint titer is predictive of vaccine effectiveness against mpox. A significant correlation was found between vaccine effectiveness and vaccinia-binding antibody titers, suggesting that antibody levels may be a correlate of protection. Combining this data with analysis of antibody kinetics after vaccination, the study predicts 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, potentially optimal in outbreaks with limited vaccine stock. Mpox, caused by the monkeypox virus, is endemic in West Africa with significant outbreaks occurring in the 1980s and 1990s. Since 2017, there has been a resurgence of mpox in Nigeria, the Democratic Republic of the Congo, and other parts of Africa, attributed to waning immunity from smallpox vaccines and accumulation of unvaccinated cohorts. In 2022, a global outbreak of mpox resulted in over 91,000 confirmed cases in 115 countries, leading to renewed focus on vaccination as a preventative measure. Although there is no mpox-specific vaccine, first-generation smallpox vaccination was observed to protect individuals against mpox infection during the 1980–1986 outbreak in the DRC, with an estimated vaccine effectiveness of approximately 85%. However, live-replicating vaccinia vaccines have significant risks of serious adverse events, leading to the development of the third-generation MVA-BN vaccine. MVA-BN was approved by the FDA for use as a smallpox and mpox vaccine, with two doses of 1×10⁸ TCID via subcutaneous injection. Regulatory approval was based on demonstrated non-inferior immunogenicity profile and improved safety compared to the second-generation ACAM2000 vaccine. The study found that one dose of MVA-BN provided similar effectiveness to historic vaccination, while two doses provided higher effectiveness. A significant benefit of two-dose vaccination over one-dose vaccination was observed. The study also found that vaccinia-binding titers are a correlate of vaccine effectiveness, with higher titers associated with higher effectiveness. The study predicts that delaying the second dose of MVA-BN vaccination provides more durable protection and may be optimal in outbreaks with limited vaccine stock. The study also predicts that vaccine effectiveness remains high for up to 10 years after a single dose, consistent with reports of long-term protection from first- and second-generation vaccines. The study highlights the importance of understanding mpox vaccination and