Pathway design shapes impact and cost in infant respiratory syncytial virus prevention

Background

Maternal vaccination against respiratory syncytial virus (RSV) and monoclonal antibodies (nirsevimab) targeting the RSV F protein are effective options for preventing severe RSV disease in infants. We assessed the cost-effectiveness of alternative maternal–infant RSV prevention pathways from the healthcare system perspective.

Methods

We developed a calibrated seasonal cohort model of the Italian birth population, reproducing RSV hospitalisations. We compared nirsevimab-only, maternal-only (40% and 55% coverage), and sequential strategies combining maternal vaccination with nirsevimab for infants not protected antenatally. Effectiveness inputs were taken from clinical trials and real-world studies. We also considered administration times, seasonal exposure, maternal indirect protection, and the specific costs associated with each pathway. Outcomes were hospitalisations averted and net costs.

Results

Preliminary results show that nirsevimab-only programmes prevented about 9,966 hospitalisations annually, with a net cost of €5.59 million. Maternal-only strategies reduced costs but prevented substantially fewer hospitalisations. Sequential strategies performed differently depending on how they were deployed. When used to expand effective protection, they increased impact while reducing costs, preventing up to 10,563 hospitalisations (+598 vs nirsevimab-only) with net savings of €1.22 million. When calibrated to the same number of hospitalisations avoided, sequential strategies consistently reduced costs (up to −€1.55 million).

Conclusions

Sequential maternal–infant strategies are not inherently superior, but their value lies in flexibility: they can expand population protection at lower cost or preserve clinical outcomes while reducing expenditure. These findings are likely generalisable to similar European settings, informing RSV prevention policy and highlighting that how prevention is organised and delivered matters as much as the intervention itself.

Key messages

• Respiratory syncytial virus prevention should be framed as pathway design, not product choice, as timing, coverage, and delivery shape real-world impact.

• Combining maternal vaccination with nirsevimab can expand protection or maintain outcomes at lower cost, offering flexible options for European health systems.