Mpox can cause severe complications in vulnerable groups such as pregnant women and children, necessitating targeted public health interventions and vaccine trials in these populations. Limited data suggest the MVA-BN vaccine is safe for pregnant women and likely poses no risk to breastfed infants, but comprehensive human data are lacking. Trials in endemic areas are crucial for evaluating the vaccine's safety and efficacy in real-world settings. Vaccine hesitancy, exacerbated by misinformation and distrust in healthcare systems, poses a significant challenge, especially in the Democratic Republic of the Congo. Pregnant women are particularly affected by concerns about vaccine safety, which influences their willingness to vaccinate. Addressing these concerns through targeted communication and community engagement is vital. A proposed phase 3, randomized trial will assess the safety and immunogenicity of the MVA-BN vaccine in healthy pregnant and postpartum women and in infants/children (6-24 months old). Additionally, a qualitative study on vaccine hesitancy will inform the trial design and implementation, aiming to enhance vaccination uptake in these high-risk groups.