RSV PREVENTION FOR ALL INFANTS: Considerations for implementation of maternal vaccination or infant immunisation in the Netherlands.

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections in infants and young children worldwide, with the highest burden under six months of age. Passive immunisation via maternal vaccination or infant immunisation are effective strategies to protect young infants from RSV disease.

In 2023, two preventive options (monoclonal antibody and maternal vaccine) to prevent RSV disease in all infants were market approved by the FDA and EMA. After approval, policymakers must decide whether to implement (one of) these new options into the national immunisation programme (NIP). The Dutch Health council gives advice, guided by available information, including data on disease burden, vaccine safety and efficacy, cost-effectiveness and acceptance of the strategy in the population. This thesis aimed to provide data to support the introduction of RSV immunisation to prevent RSV disease in all Dutch infants.

Our research showed that the full burden of RSV-related Paediatric Intensive Care Unit (PICU) admissions, extends beyond incidence measurements. The care for infants with severe RSV disease involves invasive interventions, which carry risks of complications. One-tenth of admitted infants experienced unwanted, detrimental events, including intubation injuries. To show the economic impact, we quantified total annual costs of RSV-related PICU admissions in infants from the healthcare perspective. We estimated that total yearly costs were €3.1 to €3.8 million and that potential costs averted by RSV preventive interventions are €1.9 to €2.6 million depending on the season, uptake and duration of protection.

We also systematically evaluated that maternal RSV vaccination is safe and effective. The duration of protection of maternal RSV vaccines is highly influenced by transplacental antibody transfer. Therefore, we evaluated factors that may influence antibody transfer and decay after birth. We found that variations in placental histology seem not to impact the transplacental transfer. In addition, antibody decay is strongly influenced by cord blood antibody levels. Failing to account for these kinetics leads to an overestimation of the effectiveness gap between preterm and term born infants.

Ultimately, the acceptance and uptake of vaccines is needed for successful implementation in the NIP. Therefore, we explored RSV immunisation attitudes in pregnant women. Most women expressed a positive attitude to obtain either RSV preventive option, but preferred maternal vaccination over infant immunisation. The most important influencing factors were protection against RSV disease and the safety of immunisation for the child during pregnancy and after birth. Advice of healthcare professionals was considered an important factor in vaccine decision making.

The discussion of this thesis reflects on the considerations of the Health council in view of newly emerged evidence. Given the comparable safety and efficacy, combined with the decline in vaccine coverage, allowing an individual choice using the shared decision-making approach, may help to ensure RSV immunisation uptake. In an ideal setting, vaccine information is provided by a trained healthcare professional who is also competent to administer the vaccine immediately afterwards. Continuous and active evaluation of the shared decision-making approach should assess its impact on the NIP uptake.