Source: Jabagi M-J, Bertrand M, Gabet A, et al. Nirsevimab vs RSVpreF vaccine for respiratory syncytial virus-related hospitalization in newborns. JAMA. 2026;335(9):787-798; doi: 10.1001/jama.2025.24082.Investigators from the French Agency for Medicines and Health Products Safety and French National Health Insurance, St Denis, France, conducted a cohort study to compare the effectiveness of maternal immunization with RSVpreF vaccine vs a single intramuscular dose of nirsevimab in preventing hospitalization for respiratory syncytial virus (RSV) in infants during their first RSV season. Study participants were newborns whose mothers received RSVpreF vaccine at 32–36 weeks’ gestation, or those treated with nirsevimab, who were born after September 1, 2024 and discharged from their birth hospitalization between October 1 and December 31, 2024. Infants in the RSVpreF vaccine group were matched 1:1 with an infant in the nirsevimab cohort, with matching on date of discharge, sex, gestational age (≥37 weeks or <37 weeks), and region of residence. If a patient in the RSVpreF vaccine cohort could not be matched on these criteria with one in the nirsevimab group, they were excluded from the analysis. Multiple national databases were used to collect demographic and clinical data on study participants. The primary outcome was hospitalization for an RSV respiratory tract infection between October 2024 and February 2025. A propensity score, incorporating multiple demographic and clinical characteristics, was calculated on study participants to estimate probability of treatment. Cox proportional hazard regression, with inverse probability of treatment weighting, was used to compare hospitalization rates between patients in the 2 cohorts. Among those hospitalized, the rate of PICU admission for RSV, use of supplemental oxygen treatment, or need for noninvasive or invasive ventilator support were compared between infants in the 2 cohorts.A total of 85,476 newborns met study eligibility criteria, with 62,340 (72.9%) receiving nirsevimab and 23,136 (27.1%) in the RSVpreF vaccine cohort. The study population consisted of 21,280 infants in the RSVpreF vaccine cohort (92% of those eligible) matched 1:1 with 21,280 infants who received nirsevimab. Among the 42,560 patients included in the analyses, 98.7% were born at ≥37 weeks’ gestation and had a mean follow-up of 84 days. A significantly lower percentage of participants in the nirsevimab cohort were hospitalized with RSV than among those in the RSVpreF vaccine group (1.0% vs 1.3%; adjusted hazard ratio aHR, 0.74; 95% confidence interval CI, 0.61, 0.88). Among those hospitalized, fewer patients in the nirsevimab group required PICU admissions than those in the RSVpreF vaccine cohort (25.9% vs 37.5%; P = 0.007) and were less likely to require supplemental oxygen (18.4% vs 28.3%; P = 0.01) or require ventilator support (24.1% vs 33.1%; P = 0.03).The authors conclude that nirsevimab provided better prevention of RSV hospitalization in young infants than maternal RSVpreF vaccination.Dr Loyal has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.In the current French nationwide study during the 2024–2025 RSV season, nirsevimab was associated with lower RSV-related hospitalization and severe disease in newborns compared with maternal RSVpreF vaccination, representing an important head-to-head comparison of these strategies. The study provides additional information for institutions seeking to develop their own process while factoring in recommendations from public health entities.According to the authors of the current study, nirsevimab provides passive immunity for nearly 4 months, whereas maternal RSVpreF effectiveness depends on administration within a limited gestational window and on adequate placental antibody transfer. The resultant lower immunity potentially explains why infants in the RSVpreF group had higher severity when hospitalized (PICU admission, supplemental oxygen, or ventilator support).Current US recommendations include both maternal and neonatal immunization to maximize benefits.1 The AAP recommends RSV immunoprophylaxis in infants <8 months of age during the RSV season if the pregnant parent did not receive RSVpreF during the current pregnancy, RSVpreF vaccination status is unknown, or the infant was born <14 days after RSVpreF administration.1 This recommendation appears to suggest that maternal vaccination alone is sufficient protection provided the timing is correct. The AAP and ACIP further modified their recommendations for the 2025–26 RSV season to recommend RSV monoclonal antibody in infants born to mothers who have medical conditions associated with reduced transplacental antibody transfer.The safety profile of RSVpreF is largely positive.1-3 Given the findings of the current study, however, maternal immunization alone might not be enough protection.Compared with maternal RSVpreF vaccination, nirsevimab appears to be associated with lower risks of RSV-related hospitalization and severe outcomes in young infants. (See AAP Grand Rounds. 2024;525:51.)4It goes without saying that the results of the current study require replication in additional countries and RSV seasons.
A 2026 study studied this question.