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Introduction: Maternal vaccination is a promising strategy to reduce the burden of vaccine-preventable diseases for mothers and infants. We aimed to provide an up-to-date overview of the efficacy and safety of all available maternal vaccines., Methods: We searched PubMed, Embase, CENTRAL and ClinicalTrials.gov on 1 February 2022, for phase III and IV randomised controlled trials (RCTs) that compared maternal vaccination against any pathogen with placebo or no vaccination. Primary outcomes were laboratory-confirmed or clinically confirmed disease in mothers and infants. Secondary safety outcomes included intrauterine growth restriction, stillbirth, maternal death, preterm birth, congenital malformations and infant death. Random effects meta-analysis were used to calculate pooled risk ratio's (RR). Quality appraisal was performed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE)., Results: Six RCTs on four maternal vaccines, influenza, tetanus, diphtheria and pertussis (Tdap), pneumococcal and respiratory syncytial virus (RSV) were eligible. The overall risk of bias and certainty of evidence varied from low to high. Maternal influenza vaccination significantly reduced the number of laboratory-confirmed influenza cases (RR 0.58, 95% CI 0.42 to 0.79, event rate 57 vs 98, 2 RCTs, n=6003, I 2 =0%), and clinically confirmed influenza cases in mothers (RR 0.88, 95% CI 0.78 to 0.99, event rate 418 vs 472, 2 RCTs, n=6003, I 2 =0%), and laboratory-confirmed influenza in infants (RR 0.66, 95% CI 0.52 to 0.85, event rate 98 vs 148, 2 RCTs, n=5883, I 2 =0%), although this was not significant for clinically confirmed influenza in infants (RR 0.99, 95% CI 0.94 to 1.05, event rate 1371 vs 1378, 2 RCTs, n=5883, I 2 =0%). No efficacy data were available on maternal Tdap vaccination. Maternal pneumococcal vaccination did not reduce laboratory-confirmed and clinically confirmed middle ear disease (RR 0.49, 95% CI 0.24 to 1.02, event rate 9 vs 18, 1 RCT, n=133 and RR 0.88 95% CI 0.69 to 1.12, event rate 42 vs 47, 1 RCT, n=133, respectively), and clinically confirmed lower-respiratory tract infection (LRTI) (RR 1.08, 95% CI 0.82 to 1.43, event rate 18 vs 34, 1 RCT, n=70) in infants. Maternal RSV vaccination did not reduce laboratory-confirmed RSV LRTI in infants (RR 0.75, 95% CI 0.56 to 1.01, event rate 103 vs 71, 1 RCT, n=4527). There was no evidence of a significant effect of any of the maternal vaccines on the reported safety outcomes., Conclusions: The few RCTs with low event rates suggest that, depending on the type of maternal vaccine, the vaccine might effectively prevent disease and within its size does not show safety concerns in mothers and infants., Prospero Registration Number: CRD42021235115., Competing Interests: Competing interests: JW participated in the advisory board of Janssen with fees paid to UMCU. MS leads a department that conducts studies on COVID-19 vaccines for the European Medicines Agency, Pfizer, AstraZeneca and Janssen. All according to the ENCePP code of conduct. KB is principal investigator of a phase 3 clinical trial on maternal RSV vaccination funded by Pfizer and of work package three of the Consign study funded by EMA. LJB has regular interaction with pharmaceutical and other industrial partners. He has not received personal fees or other personal benefits. UMCU has received major funding (>€100 000 per industrial partner) for investigator initiated studies from AbbVie, MedImmune, Janssen, the Bill and Melinda Gates Foundation, Nutricia (Danone) and MeMed Diagnostics. UMCU has received major cash or in kind funding as part of the public private partnership IMI-funded RESCEU project from GSK, Novavax, Janssen, AstraZeneca, Pfizer and Sanofi. UMCU has received major funding by Julius Clinical for participating in the INFORM study sponsored by MedImmune. UMCU has received minor funding for participation in trials by Regeneron and Janssen from 2015 to 2017 (total annual estimate less than €20 000). UMCU received minor funding for consultation and invited lectures by AbbVie, MedImmune, Ablynx, Bavaria Nordic, MabXience, Novavax, Pfizer, Janssen (total annual estimate less than €20 000). LJB is the founding chairman of the ReSViNET Foundation. All other authors have nothing to disclose (OB, EP, FA and NvdM)., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Respiratory syncytial virus (RSV) imposes a substantial burden on pediatric hospital capacity in Europe. Promising prophylactic interventions against RSV including monoclonal antibodies (mAb) and maternal immunizations (MI) are close to licensure. Therefore, we aimed to evaluate the cost-effectiveness of potential mAb and MI interventions against RSV in infants, for six European countries., Methods: We used a static cohort model to compare costs and health effects of four intervention programs to no program and to each other: year-round MI, year-round mAb, seasonal mAb (October to April), and seasonal mAb plus a catch-up program in October. Input parameters were obtained from national registries and literature. Influential input parameters were identified with the expected value of partial perfect information and extensive scenario analyses (including the impact of interventions on wheezing and asthma)., Results: From the health care payer perspective, and at a price of €50 per dose (mAb and MI), seasonal mAb plus catch-up was cost-saving in Scotland, and cost-effective for willingness-to-pay (WTP) values ≥€20,000 (England, Finland) or €30,000 (Denmark) per quality adjusted life-year (QALY) gained for all scenarios considered, except when using ICD-10 based hospitalization data. For the Netherlands, seasonal mAb was preferred (WTP value: €30,000-€90,000) for most scenarios. For Veneto region (Italy), either seasonal mAb with or without catch-up or MI was preferred, depending on the scenario and WTP value. From a full societal perspective (including leisure time lost), the seasonal mAb plus catch-up program was cost-saving for all countries except the Netherlands., Conclusion: The choice between a MI or mAb program depends on the level and duration of protection, price, availability, and feasibility of such programs, which should be based on the latest available evidence. Future research should focus on measuring accurately age-specific RSV-attributable hospitalizations in very young children., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘PB reports grants from Respiratory Syncytial Virus Consortium in Europe (RESCEU), Innovative Medicines Initiative 2 of the European Commission, Joint Undertaking under grant agreement No 116,019 during the conduct of the study; and grants from Pfizer, GSK, Merck and European Commission IMI project PROMISE, outside the submitted work, but he has not received any personal fees or other personal benefits. LB’s institution, UMCU has received major funding (>€100,000 per industrial partner) for investigator initiated studies from AbbVie, MedImmune, AstraZeneca, Sanofi, Janssen, Pfizer, MSD and MeMed Diagnostics. UMCU has received major funding for the RSV GOLD study from the Bill and Melinda Gates Foundation and major funding as part of the public private partnership IMI-funded projects (RESCEU and PROMISE). UMCU also has received major funding by Julius Clinical for participating in clinical studies sponsored by MedImmune and Pfizer and minor funding (€1,000–25,000 per industrial partner) for consultation and invited lectures by AbbVie, MedImmune, Ablynx, Bavaria Nordic, MabXience, GSK, Novavax, Pfizer, Moderna. TH declared consultancy fees from Sanofi and Janssen for Ad hoc advisory board meeting and honoraria for Lecture on the burden of RSV in children from Jassen and MSD, outside the submitted work. JvS’s institution, Nivel has received unrestricted research grants from WHO, Sanofi and the Foundation for Influenza Epidemiology for work outside the submitted work. CR declared consultancy fees for Ad hoc advisory board meeting and honoraria for Lecture from Seqirus, MSD, Sanofi, outside of the submitted work. ST was an employee of IVIDATA during the conduct of the study, and her employer received consultancy fees from Sanofi. All other authors report no potential conflicts.’, (Copyright © 2023 Elsevier Ltd. All rights reserved.)