Maternal vaccine RWE: where post-authorisation evidence matters

Maternal immunisation is one of the priority research areas in the European Medicines Agency’s updated Vaccine Monitoring Platform (VMP) research agenda for 2026–2029. The agenda calls for further evidence on the effectiveness and safety of vaccination during pregnancy.

According to FVR’s Lead Medical Expert Santtu Heinonen, MD, PhD, specialist in paediatrics and paediatric infectious diseases, the key post-authorisation questions include effectiveness in routine use, safety at scale and, in maternal vaccination specifically, outcomes in both the mother and the child.

When the disease endpoint is difficult to study directly

Group B Streptococcus (GBS) is an example where studying the clinical disease endpoint directly is difficult.

“GBS can cause severe infections in newborns, including sepsis, meningitis and pneumonia. In Finland, screening and intrapartum antibiotic prophylaxis have substantially reduced early-onset disease, but do not prevent late-onset GBS disease,” Santtu says.

Maternal GBS vaccines are in clinical development. FVR is currently conducting a study in Finland, which evaluates an investigational GBS vaccine in pregnant women, including antibody formation in the mother, transfer of antibodies to the infant and vaccine safety.

“Because severe GBS disease is a relatively rare clinical endpoint, studying vaccine efficacy against the disease itself would require very large populations. The use of correlates of protection – antibody levels associated with protection – is one way of addressing this in vaccine development,” Santtu explains.

EMA’s VMP agenda identifies the same issue. It notes that approval of GBS vaccines is likely to rely on surrogate efficacy markers because clinical efficacy studies would be difficult to conduct within realistic timelines. It therefore highlights post-authorisation effectiveness and safety data as important for assessing protection against early- and late-onset GBS disease and for identifying rare or very rare safety issues.

“Where authorisation is based on immunogenicity data, evidence from much larger populations can later show whether disease decreases in line with the conclusions drawn from the antibody data. This evidence could come from RWE, a large Phase IV study or a pragmatic trial,” Santtu says.

Following both mother and child

Maternal immunisation requires outcomes to be considered in both the mother and the child. For some vaccines, such as influenza and COVID-19, maternal protection is central. With maternal pertussis and RSV vaccination, protection of the infant through maternally derived antibodies is the main outcome.

“For post-authorisation research, this means linking vaccination during pregnancy with pregnancy and delivery outcomes in the mother and health outcomes in the child. Infant follow-up in trials often ends at around six months or a year, whereas linked health data can potentially support much longer follow-up of later safety and longer-term health outcomes,” says Santtu.

Linking register data with biological samples

Finland’s national registers allow pregnancy and vaccination information to be linked with birth data and subsequent health outcomes in the child.

“For some research questions, register data can also be combined with biological samples. For example, Finnish researchers have used stored cord-blood samples together with register data to study antibody levels in infants who subsequently developed GBS disease. Finland also offers opportunities to combine longitudinal register data with biobank and other research samples,” Santtu says.

Why timing matters

According to Santtu, FVR sometimes discusses potential RWE projects with vaccine developers before marketing authorisation. “Before a vaccine becomes part of a national vaccination programme, there may be an opportunity to conduct a pragmatic randomised trial. Once a vaccine is incorporated into a national vaccination programme, a randomised pragmatic trial may no longer be feasible, and follow-up is more likely to rely on observational data.”

EMA’s agenda specifically identifies post-authorisation effectiveness and safety evidence as a research need in maternal immunisation, including in GBS vaccine development.

Links:

EMA Vaccine Monitoring Platform (VMP) research agenda: https://www.ema.europa.eu/en/documents/other/vaccine-monitoring-platform-vmp-research-agenda-update-2026_en.pdf

Lancet: https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(24)00038-7/fulltext

In Finnish: https://helda.helsinki.fi/server/api/core/bitstreams/bdfc04fe-1a35-4cf4-a6f6-042fd48f70a4/content

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