PregInPoxVac maternal protocol: a phase 3 trial evaluating maternal immunogenicity and safety of the MVA-BN vaccine in the Democratic Republic of the Congo.

Abstract

Mpox remains endemic in the Democratic Republic of the Congo (DRC), with pregnant women at increased risk of severe disease and adverse outcomes. The WHO has called for data on mpox vaccination in high-risk groups, but no clinical trial has assessed the safety or immunogenicity of mpox vaccines in this population. The modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine, a third-generation, highly attenuated, non-replicating, live virus vaccine, has shown an excellent safety profile in adolescents and adults, including immunocompromised individuals, and is expected to be safe during pregnancy. Pregnancy & Infancy mPox Vaccine study is a phase 3, open-label trial that aims to evaluate the safety, reactogenicity and immunogenicity of the MVA-BN vaccine in pregnant and postpartum women in Boende, the DRC, compared with adults of the POX-MVA-045 study (NCT06549530) in DRC and Uganda. A total of 359 pregnant women (16-35 years old, in their second or third trimester of pregnancy) are being enrolled and randomised to receive the homologous MVA-BN vaccine regimen at a 28-day interval, with the first dose administered either before 32 weeks of gestation during pregnancy or within 72 hours postpartum (3:2 ratio randomisation). An additional, non-randomised group will receive post-exposure prophylaxis following confirmed mpox exposure. Primary immunogenicity analyses will assess the non-inferiority of neutralising antibody titres in pregnant women compared with those in non-pregnant adults. Primary safety analyses will compare reactogenicity in pregnant women to that observed in adults and safety in pregnant women to safety observed in adults and women vaccinated in the immediate postpartum period. Secondary analysis will evaluate neutralising antibody titres and total binding antibody concentrations over time for pregnant and postpartum women compared with adults and each other. The trial integrates ancillary care pathways, local capacity building and formative workshops that co-developed research tools. Ethical approvals were obtained from institutional and national review boards in the DRC and Belgium. Results will be shared with local communities, national stakeholders and global health agencies. NCT06844500 & PACTR202511506487215.