Europe stands at a pivotal moment for maternal vaccines

Maternal immunisation is entering the most consequential phase in its history. With the first regulatory approvals of respiratory syncytial virus (RSV) vaccines for use in pregnancy and late-stage clinical development of vaccines against group B streptococcus (GBS), Europe stands on the threshold of a major expansion of maternal vaccine programmes. A narrative Review published in The Lancet Regional Health – Europe by Paul T. Heath of City St George’s, University of London, and colleagues argues that scientific progress alone will not be enough. Without coordinated regulatory, health-system, and societal readiness, the next generation of maternal vaccines risks reproducing the inequities, delays, and implementation failures seen in previous rollouts, from influenza to COVID-19.

The biological logic of maternal vaccination is well established. Vaccines given during pregnancy induce maternal antibodies that cross the placenta, protecting both the pregnant woman and her infant during the first months of life. Protection of the infant occurs primarily through active transplacental transfer of vaccine-induced maternal immunoglobulin G (IgG), a process that increases exponentially across gestation and is modulated by maternal antibody concentration, IgG subclass, placental function, and maternal health. Because placentally transferred IgG decays in the infant with a half-life of roughly 30 days, the duration of passive protection typically spans four to six months. Transfer occurs mainly via the neonatal Fc receptor expressed on syncytiotrophoblasts, peaking in the third trimester, and is influenced by antibody glycosylation, total maternal IgG concentration, maternal health status, and infant birthweight.

Timing, however, is not a simple equation. Vaccination late in pregnancy may not allow sufficient time for peak antibody generation and placental transfer before delivery, whereas earlier vaccination supports antibody maturation but may leave maternal antibody concentrations waning by the time of birth. The interval between vaccination and delivery strongly influences cord blood antibody concentrations and thereby the duration of neonatal protection. Evidence from the United Kingdom shows that although early third-trimester pertussis vaccination yields higher vaccine effectiveness, a wider vaccination window achieves better overall coverage. For RSV and pertussis, where disease burden extends into the first months of life, both antibody concentrations at birth and their persistence matter. For early-onset GBS disease, which strikes immediately after birth, maternal vaccination must achieve sufficiently high antibody concentrations at delivery. Preterm infants, who are more susceptible to infection and have reduced cumulative IgG transfer, add a further layer of complexity, as do maternal comorbidities such as HIV infection and chronic inflammation, which impair placental IgG transfer.

The COVID-19 pandemic generated unprecedented evidence on vaccination in pregnancy across multiple platforms. Although pregnant women were largely excluded from initial clinical trials despite their increased burden of severe disease, widespread deployment and subsequent observational studies demonstrated that vaccine-induced antibodies were efficiently transferred across the placenta and detectable in breast milk. Systematic reviews and meta-analyses consistently found no increase in adverse pregnancy or neonatal outcomes, and large cohort studies showed that maternal mRNA vaccination reduced the risk of severe COVID-19 in both the pregnant woman and her infant. Comparative studies found mRNA vaccines more immunogenic than adenoviral vector vaccines such as Ad26.CoV2.S or ChAdOx1-S. The pandemic also accelerated European regulatory and pharmacovigilance infrastructure, expanding pregnancy exposure registries, active surveillance programmes, and data linkage capabilities that enabled real-time safety assessment.

The RSV vaccine story illustrates both the promise and the fragility of maternal immunisation. RSV is a leading cause of lower respiratory tract disease and hospitalisation in infants under six months of age. Prefusion F (preF) protein-based vaccines target stabilised conformations of the RSV fusion glycoprotein, inducing high-titre, affinity-matured neutralising antibodies that cross the placenta efficiently. Clinical trials demonstrated efficacy against severe infant disease, and real-world effectiveness data from Scotland and France support these findings. Yet safety monitoring remains critical. An earlier preF vaccine candidate was discontinued after a preterm birth safety signal, and the pivotal trial of the now-licensed Pfizer preF vaccine showed excess prematurity among South African participants (relative risk 2.06, 95% CI 1.21–3.51), though not in other countries or the trial overall. Emerging post-licensure data provide reassurance, but sustained confidence depends on ongoing surveillance. An mRNA RSV vaccine candidate is now in phase 2 testing in pregnancy, and long-acting monoclonal antibodies such as nirsevimab and clesrovimab offer an alternative passive strategy, with recent observational studies suggesting slightly greater protection against RSV-related hospitalisation than maternal vaccination.

GBS vaccines are advancing beyond antigen discovery toward late-phase evaluation. Current candidates follow two strategies: capsular-polysaccharide protein conjugates and protein-based vaccines. Pfizer’s investigational hexavalent conjugate GBS6 showed acceptable safety and efficient antibody transfer to infants in a phase 2 maternal study and has progressed to phase 3. In parallel, MinervaX’s GBS-AlpN, a multicomponent protein subunit vaccine composed of N-terminal domains from alpha-like proteins selected to maximise strain coverage, showed an acceptable safety profile and vaccine-specific antibody responses in mothers and infants, also supporting phase 3 progression. Harmonised assays and standardised immunological thresholds will be critical to support immunobridging approaches and conditional licensure, allowing widespread implementation before full efficacy data accumulate.

New platforms are reshaping the pipeline. With the exception of live attenuated vaccines, which are contraindicated in pregnancy, and DNA vaccines, which lack pregnancy-specific safety data, inactivated, subunit, toxoid, viral vector, mRNA, and virus-like particle platforms are all suitable for use during pregnancy. mRNA technology is opening doors to pathogens without licensed vaccines and to combination products. A phase 3 trial of an mRNA quadrivalent influenza vaccine showed superior efficacy against influenza-like illness compared with a licensed inactivated vaccine, with a relative efficacy of 34.5% (95% CI 7.4–53.9). The CHMP of the European Medicines Agency has provided a positive opinion recommending marketing authorisation for Moderna’s mCOMBRIAX, a combination influenza and COVID-19 vaccine that was at least as immunogenic as standard-of-care vaccines with an acceptable safety profile. Combination vaccines may improve acceptability as the number of recommended maternal vaccines grows, but they raise theoretical concerns: vaccines targeting seasonal infections must balance optimal gestational timing against seasonal campaign timing, and co-administered products may compromise the individual gestational timing needed for maximal infant effectiveness.

The pipeline extends to emerging and priority pathogens. Zika virus vaccine candidates aimed at preventing fetal transmission remain in early-phase development, slowed by low current incidence. Lassa fever carries a case fatality rate of approximately 34% in pregnancy and 67–75% in neonates, yet pregnant women remain excluded from ongoing trials. Ebola vaccines were licensed without pregnancy-specific data, though WHO recommended their use during outbreaks and a large study has since demonstrated the safety of the two-dose Ad26.ZEBOV/MVA-BN-Filo regimen in pregnancy. The only WHO-prequalified mpox vaccine, MVA-BN, is not currently recommended for pregnant women, though the PregInPoxVac study is now assessing safety and immunogenicity in pregnancy. Among bacterial threats, Klebsiella pneumoniae, classified by WHO as a priority 1 pathogen, is a major cause of neonatal sepsis with increasing antibiotic resistance; a modelling study concluded that an effective maternal vaccine could prevent around 80,000 neonatal deaths and 399,000 neonatal sepsis cases annually. A phase 1/2 trial of the tetravalent bioconjugate vaccine Kleb4V recently demonstrated acceptable safety and immunogenicity. Escherichia coli vaccine candidates are in preclinical and early clinical development, though the nine-valent ExPEC9V conjugate vaccine failed to demonstrate sufficient efficacy in a phase 3 trial in older adults. Congenital cytomegalovirus, the most common congenital infection globally and the leading non-genetic cause of sensorineural hearing loss, has defeated vaccine development for more than five decades; the failure of the most advanced candidate, an mRNA vaccine encoding glycoprotein B and the pentameric complex, underscores the difficulty of preventing primary infection and may prompt renewed scrutiny of antigen selection and clinical endpoints.

Regulatory readiness is advancing but unevenly. The EMA evaluates vaccines for pregnancy via its standard centralised assessment, with targeted initiatives including pre- and post-authorisation evidence strategies, regulatory cluster collaborations with the FDA and MHRA, and promotion of pregnant women’s inclusion in clinical research where ethical and scientific justification allow. Post-marketing surveillance is governed by Good Pharmacovigilance Practices, requiring Risk Management Plans and Periodic Safety Update Reports, with collaborative networks such as ENCePP and the ACCESS project supporting systematic monitoring. Yet a central challenge lies beyond the licensing stage: following EMA approval, decisions on recommendation by National Immunisation Technical Advisory Groups, reimbursement, procurement, inclusion in national schedules, and service delivery remain the responsibility of individual countries. The recent rollout of maternal RSV immunisation illustrates this fragmentation, with countries differing considerably in policy recommendations, implementation timelines, funding mechanisms, and delivery pathways. The authors propose a European Maternal Immunisation Preparedness Plan (EMIPP), developed by a European coordination group with representation from vaccine developers, regulators, public health and communications experts, implementation specialists, and patient groups.

Equity and confidence are the final determinants of success. Lower uptake of all maternal vaccines has consistently been associated with socioeconomic deprivation, lower educational attainment, migrant and minority backgrounds, language barriers, limited antenatal care engagement, and lower trust in healthcare institutions. Public concerns about insufficient long-term safety data and unknown effects on the developing fetus are recurring themes, heightened when the vaccine or platform is new; the exclusion of pregnant women from trials created a data void rapidly filled by misinformation during the COVID-19 pandemic. A meta-analysis found that pregnant women who received a provider recommendation had ten to twelve times higher odds of accepting pertussis or influenza vaccination, yet communication training for obstetric and midwife providers remains limited. The commercial case also needs attention: the maternal vaccine market has historically been perceived as small, with higher development costs and more complex regulatory requirements, and addressing these barriers will require coordinated action from regulators, public funders, policymakers, and industry, including push incentives such as research grants and pull incentives such as advance market commitments. A European precedent already exists: in January 2026, VacPertagen, a recombinant acellular pertussis vaccine, received EU marketing authorisation on the basis of comparative immunogenicity rather than clinical efficacy, with post-marketing studies stipulated to confirm effectiveness and pregnancy safety. As the authors conclude, realising the potential of the next generation of vaccines in pregnancy will require integrated action across research, regulation, implementation, and communication. Europe is well positioned to lead, but only with deliberate, coordinated investment in equitable delivery.

Subject of Research: The next generation of maternal vaccines: scientific advances, regulatory readiness, and strategic planning in Europe

Article Title: The next generation of maternal vaccines: scientific advances, regulatory readiness, and strategic planning in Europe

Article References: Heath, P. T., Galiza, E. P., Salcedo, P. J., Karafillakis, E., Khalil, A., Maertens, K., Le Doare, K., & Jones, C. E. (2026). The next generation of maternal vaccines: scientific advances, regulatory readiness, and strategic planning in Europe. The Lancet Regional Health – Europe, 71, Article 101899. https://doi.org/10.1016/j.lanepe.2026.101899

Image Credits: AI Generated

DOI: 10.1016/j.lanepe.2026.101899

Keywords: next, generation, maternal, vaccines, scientific, advances, regulatory, readiness, strategic, planning, Europe, scientific research