Thesis defense Joukje Willemsen

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Respiratory syncytial virus (RSV) is a major cause of infant mortality, particularly in low- and middle-income countries (LMICs), where new preventive strategies such as maternal vaccination are not yet widely accessible. This thesis aimed to inform cost-effectiveness modelling and decision-making by estimating the potential impact of maternal RSV vaccination on mortality in LMICs. To achieve this, an existing mathematical model was refined using updated epidemiological, immunological, and clinical trial data, and key assumptions were validated.

We examined age-at-death distributions in infancy, showing that data collection methods strongly influence estimates and that retrospective data may underestimate the potential impact of vaccination. We integrated updated evidence into an impact model, identifying optimal vaccination timing during pregnancy and incorporating realistic antenatal care coverage across countries. Maternal vaccination could avert a substantial proportion of RSV-related deaths. Because the recommended vaccination window in the United States is currently more restrictive than in Europe, we modelled the impact of adopting a similarly restricted window in LMICs, which reduced the potential mortality benefit.

Finally, we evaluated immunological assumptions and clinical trial design considerations. Antibody decay in early life appeared to depend on antibody levels at birth, suggesting smaller differences in protection between preterm and term infants than previously thought. We also highlight the need for clinical trials that better align with modelling and policy needs. Overall, this thesis shows that combining improved burden estimates, immunologically informed protection, and realistic delivery assumptions is essential to guide the optimal use of maternal RSV vaccination in LMICs.