PregInPoxVac

The challenge

The monkeypox virus (MPXV), the causing agent of mpox, can have particularly severe impacts on little children, where it can lead to severe complications and high mortality. Also, pregnant women are at increased risk, affecting both their health and that of their unborn babies. Infections during pregnancy can lead to a range of adverse pregnancy outcomes, including neonatal infections, stillbirths, premature delivery and low birthweight. 

The MVA-BN vaccine offers good protection against mpox infection. However, there are limited data on its use in infants and pregnant women. Additionally, in infants, available safety data in paediatric populations support the rationale for evaluating a reduced (half) dose. A lower dose may provide comparable immune responses while potentially reducing reactogenicity, but this needs to be confirmed. This approach will help determine whether a smaller dose can achieve adequate immunogenicity while minimising adverse events in this younger age group.

In pregnant women, there is no indication that the MVA-BN vaccine would be unsafe, particularly given its non-replicating nature. However, its safety and immunogenicity in this population still need to be formally evaluated. In addition, it remains unclear whether, and for how long, vaccinated mothers can provide protection to their newborns.

In this study, we will assess the presence of antibodies in umbilical cord blood and breastmilk of women vaccinated during pregnancy, as well as the timing of antibody appearance in women vaccinated in the immediate postpartum period. We will also evaluate whether these antibodies are transferred to infants through breastfeeding and how long they persist.

The project

The PregInPoxVac project is collecting data to assess the immunogenicity and safety of MVA-BN in infants and in pregnant women. At Boende, Tshuapa Province in the Democratic Republic of the Congo (DRC), an existing clinical trial site, 344 infants of 4 to less than 24 months will be recruited, of whom half will receive the standard vaccine regimen and half, the half-dose regimen. Further, 359 pregnant women will be recruited into a study to track immune responses following vaccination. 215 pregnant women will be vaccinated during pregnancy, and 144 in the immediate postpartum period.

As well as analysing immune responses after vaccination, the project team is also tracking birth outcomes and monitoring the health of young babies born to vaccinated women. Afterwards, vertical transmission of vaccine-induced antibodies will be assessed. In addition, a qualitative study is being carried out to assess attitudes towards Mpox, vaccination, and participation in vaccine research among pregnant women, their families, and health workers. This will inform the development of communications materials for women and their families to encourage vaccination uptake and participation in research studies. Also, a formal ancillary care policy will be rolled out to cover all study- and non-study-related adverse events during trial participation.

The PregInPoxVac project has received €5.99 million of co-funding from CEPI.

PregInPoxVac is one of nine projects funded through an emergency call for proposals launched in response to the mpox outbreak in the DRC and other sub-Saharan African countries, which was declared a Public Health Emergency of International Concern (PHEIC) by WHO and a Public Health Emergency of Continental Security (PHECS) by Africa CDC in 2024.

Impact

The PregInPoxVac project is generating vital data on vaccination of pregnant women and infants to prevent mpox infection. It will:

• Provide further high-quality data on the safety and immunogenicity of the MVA-BN vaccine in pregnant women in Africa.
• Identify whether vaccine-induced antibodies are transmitted to newborns of vaccinated mothers.
• Shed light on any potential barriers that might prevent the uptake of mpox vaccination by pregnant women.
•  Provide further high-quality data on the safety and immunogenicity of the MVA-BN vaccine in infants in Africa.
• Shed light on the use of half a dose of the MVA-BN vaccine in the infant population

With infants and pregnant women at risk of multiple adverse outcomes following infection, the PregInPoxVac project will provide policymakers with greater confidence to recommend vaccination of pregnant women and/or infants against mpox.