Effectiveness of nirsevimab immunisation after birth versus RSVpreF maternal vaccination in preventing RSV-related hospitalisations in infants: a population-based retrospective cohort study

Maternal respiratory syncytial virus (RSV) prefusion F (RSVpreF) vaccine and nirsevimab immunisation are two products recently implemented to reduce RSV-related lower respiratory tract infection (LRTI) in infants (nirsevimab since 2023 and RSVpreF since 2024). We aimed to assess the effectiveness of nirsevimab immunisation at birth versus RSVpreF maternal vaccination in preventing RSV-related LRTI hospitalisations in children before age 6 months.

This population-based retrospective cohort study used data from the French National Health Data System and included all children born across metropolitan France between Sept 1, 2024, and Feb 28, 2025, who either received nirsevimab at birth (nirsevimab group) or whose mothers received RSVpreF vaccine between 28 weeks and 36 weeks of gestation (RSVpreF group). Children who received neither immunisation, those born from mothers not aged 13-50 years, and those who could not be linked to their mother in the database were not included. Children were matched on birth date, region of birth, and sex. The primary outcome was RSV-related LRTI hospitalisation at age 6 months. Propensity score analysis adjusted for baseline characteristics. Secondary analyses were performed, notably assessing the influence of the timing of RSVpreF maternal vaccination during pregnancy on the main outcome.

During the study period, 164 140 children were included, of whom 83 978 (51·2%) were male and 80 162 (48·8%) female; mean gestation at birth was 39·4 weeks (SD 1·2), 103 062 (62·8%) received nirsevimab after birth, and 61 078 (37·2%) were born to mothers vaccinated with RSVpreF. 42 098 children from each group were matched. During the 6-month follow-up, 753 RSV-related LRTI hospitalisations occurred: 350 (0·83%) of 42 098 infants in the nirsevimab immunisation group and 403 (0·96%) of 42 098 infants in the RSVpreF vaccine group. After adjustment, nirsevimab was associated with a 22% reduction in the odds of RSV-related LRTI hospitalisation compared with RSVpreF vaccination (OR 0·78 [95% CI 0·70-0·86]). Although the odds of RSV-related LRTI hospitalisation were lower with nirsevimab than with RSVpreF vaccination when RSVpreF vaccination was given between 2 weeks and less than 4 weeks (0·45 [0·32-0·63]), between 4 weeks and less than 6 weeks (0·80 [0·68-0·95]), and between 6 weeks and less than 8 weeks before delivery (0·80 [0·60-0·99]), there was no difference between nirsevimab and RSVpreF given 8 weeks or more before delivery (1·01 [0·77-1·32]).

Compared with RSVpreF maternal vaccine, nirsevimab at birth was associated with a reduction in the odds of RSV-related LRTI hospitalisation at age 6 months in the 2024-25 RSV season. Exploratory secondary analyses suggest that an interval of at least 8 weeks between RSVpreF vaccination and delivery could provide protection not statistically different from nirsevimab at birth. These findings can guide future public health decisions.

Assistance Publique-Hôpitaux de Paris Foundation.