Collaborating with Mother Nature: The potential impact of maternal vaccination on RSV-related mortality

Abstract

Respiratory syncytial virus (RSV) is one of the leading causes of death in infants, particularly in low and middle income countries (LMICs), where new prevention options such as maternal vaccination are not yet widely available. This thesis aimed to support global health decision making by estimating the potential impact of maternal RSV vaccination on infant mortality in LMICs. First, the age at which infants die from RSV was examined; estimated age distributions were found to vary substantially depending on how data are collected. Studies based on retrospective data may underestimate the potential impact of vaccination. An existing mathematical model was improved by combining updated data on age at death, immune protection in early life, and clinical trial results. Realistic assumptions about antenatal care attendance and vaccine acceptance across different countries were also incorporated. Using these improvements, it was estimated that maternal vaccination could prevent a substantial proportion of RSV related infant deaths, ranging from 33% to 83% depending on the country, with an average of approximately 55 to 63%. The effect of changes in vaccination timing policies on this impact was also explored. If LMICs adopted a more restrictive vaccination window similar to that used in the United States, rather than the broader European recommendation, the potential reduction in infant deaths would decrease by approximately 12%. Finally, the decline of naturally acquired protective antibodies transferred from mother to infant after birth was studied. This decline was found to depend on antibody levels at birth, suggesting that differences in protection between preterm and full term infants may be smaller than previously thought. This thesis concludes that modeling frameworks combining improved burden estimates, immunologically informed protection, and realistic delivery assumptions will be critical for guiding global health decision making on RSV vaccination strategies as the prevention landscape continues to evolve.