Mpox remains endemic in the Democratic Republic of the Congo (DRC), and pregnant women are recognized as a group at increased risk of severe disease and adverse maternal and neonatal outcomes. The World Health Organization has called for evidence on mpox vaccination in high-risk populations, but prior to this study no clinical trial had assessed the safety or immunogenicity of mpox vaccines specifically in pregnancy.
The modified vaccinia Ankara—Bavarian Nordic (MVA-BN) vaccine is a third-generation, highly attenuated, non-replicating live virus vaccine. It has demonstrated an excellent safety profile in adolescents and adults, including people with immunocompromise, and is therefore considered likely to be safe for use in pregnancy. The PregInPoxVac study was designed to generate direct evidence on immunogenicity and safety of MVA-BN in pregnant and early postpartum women in a highly endemic setting.
Pregnancy & Infancy mPox Vaccine (PregInPoxVac) is a phase 3, open-label clinical trial conducted in Boende, DRC. The protocol enrols a total of 359 pregnant women aged 16–35 years who are in their second or third trimester. Participants are randomised in a 3:2 ratio to timing of the first vaccine dose: either during pregnancy (with the first dose administered before 32 weeks’ gestation) or in the immediate postpartum period (within 72 hours after delivery).
Comparative immunogenicity and safety analyses will reference adult participants enrolled in the POX-MVA-045 study (ClinicalTrials.gov identifier NCT06549530) conducted in the DRC and Uganda. In addition to the main randomized groups, the trial includes an additional, non-randomised cohort intended to receive post-exposure prophylaxis (PEP) following confirmed mpox exposure; the source did not report the size or further procedural details of this subgroup.
All randomized participants receive a homologous two-dose MVA-BN regimen, with vaccine doses given 28 days apart. Randomisation uses a 3:2 allocation to the two timing arms: first dose before 32 weeks’ gestation (during pregnancy) or first dose within 72 hours postpartum. The non-randomised PEP group will receive vaccination following documented exposure to mpox as part of post-exposure management.
The open-label design means participants and investigators are aware of vaccine administration and timing. The trial compares immune responses and safety outcomes in pregnant and postpartum women to those observed in non-pregnant adult cohorts from the referenced POX-MVA-045 study.
Primary immunogenicity analyses focus on the non-inferiority comparison of neutralising antibody titres in pregnant women versus non-pregnant adults. The study aims to determine whether the humoral immune response elicited by MVA-BN in pregnancy meets a predefined non-inferiority margin compared with adult comparators; exact statistical margins and thresholds were not reported in the source material.
Primary safety analyses include reactogenicity comparisons between pregnant women and adults, and broader safety comparisons between pregnant women and both adults and women vaccinated in the immediate postpartum period. Reactogenicity assessments and safety monitoring are integral to evaluating tolerability of the vaccine in pregnancy.
Secondary analyses will examine longitudinal immune markers, including neutralising antibody titres and total binding antibody concentrations, over time for pregnant and postpartum women and compare these dynamics with adult comparators and between the pregnancy and postpartum groups.
The trial integrates ancillary care pathways and local capacity building into its implementation. Formative workshops were used to co-develop research tools with local stakeholders. The protocol thus embeds elements intended to strengthen local clinical and research capacity while delivering trial-related care and follow-up.
Investigators plan to share trial findings and outputs with local communities, national stakeholders and global health agencies to inform mpox vaccine policy and practice in pregnancy.
Ethical approvals for the trial were obtained from institutional and national review boards in the DRC and from review authorities in Belgium. The study protocol includes plans for dissemination of results to community and policy stakeholders.
Trial registration identifiers reported in the source are NCT06844500 and PACTR202511506487215. The source did not provide trial start dates, enrollment milestones, or interim results; those details were not reported in the provided material.