Background

Population-level real-world evidence effectiveness on the newly introduced maternal RSVpreF vaccine remains limited. We estimated effectiveness and durability of protection against RSV-associated hospitalisation in infants.

Methods

Using the French National Health Data System, we conducted a nationwide study emulating a target trial among infants born between Sept 1 and Dec 31, 2024 in France. Infants born to mothers vaccinated with RSVpreF during pregnancy were matched 1:1 with unimmunised infants on exact date of birth, gestational age, sex, and deprivation status. Follow-up started at birth and continued until Feb 28, 2025. Inverse probability weighting was applied to balance measured covariates. The primary outcome was hospitalisation for RSV-associated lower respiratory tract infection (RSV-LRTI). Secondary outcomes included paediatric intensive care unit admission, oxygen therapy, and ventilatory support. Hazard ratios were estimated using Cox models, and vaccine effectiveness calculated as (1-HR) × 100.

Findings

Among 31,356 infants included in the matched cohort (15,678 per group; median follow-up 86 days [IQR 73–101]), 693 RSV-LRTI hospitalisations occurred, including 216 (1·4%) among immunised infants and 477 (3·0%) among unimmunised. Maternal RSVpreF immunisation was associated with a reduced risk of RSV-LRTI hospitalisation (HR 0·50, 95% CI 0·45–0·55), corresponding to an effectiveness of 50% (95% CI 45–55). Protection was highest during days 0–14 after birth (66%, 95% CI 58–73) and declined thereafter to 38% (95% CI 19–52) during days 60–75. Reductions were also observed for severe outcomes, including RSV-LRTI requiring paediatric intensive care unit admission (74 (0·5%) vs 158 (1·0%); effectiveness 51%, 95% CI 43–57), oxygen therapy (59 (0·4%) vs 136 (0·9%); effectiveness 54%, 95% CI 46–60), and ventilatory support (65 (0·4%) vs 137 (0·9%); effectiveness 53%, 95% CI 45–59).

Interpretation

Maternal RSVpreF immunisation reduced RSV-associated hospitalisation in infants, with protection strongest early in life and declining thereafter.