Preventing respiratory syncytial virus (RSV) in infants can be achieved through maternal vaccination with the RSV prefusion F protein (RSVpreF) vaccine or administration of the monoclonal antibody nirsevimab—strategies endorsed by the WHO. In a French population-based cohort study, nirsevimab has been associated with lower risks of RSV-related hospitalizations and severe outcomes.
“This study compared outcomes after passive immunization with nirsevimab vs RSVpreF vaccination, and its findings should not be interpreted as evidence against the efficacy of the RSVpreF vaccine,” cautioned first study author Dr Marie-Joelle Jabagi from the French National Agency for Medicines and Health Products Safety and French National Health Insurance in Saint-Denis, France, and colleagues.
In this study, follow-up was limited to a median of 84 days following discharge from the infants’ birth hospitalization. Hospitalization for RSV-associated lower respiratory tract infection (LRTI) occurred less frequently among infants who received nirsevimab than among those born to mothers vaccinated with RSVpreF (44.1 percent vs 55.9 percent; between-group difference, −11.8 percent, 95 percent confidence interval [CI], −18.1 to −5.5; p<0.001). [JAMA 2026;335:787-798]
Nirsevimab was associated with a 26-percent reduction in the risk of RSV-associated LRTI hospitalization compared with RSVpreF (adjusted hazard ratio [aHR], 0.74, 95 percent confidence interval [CI], 0.61–0.88).
In subgroup analyses, the risk of RSV-associated LRTI hospitalization was higher in the nirsevimab group than in the RSVpreF group during the first 7 days (aHR, 2.94, 95 percent CI, 1.19–7.69) and did not significantly differ between the two groups during days 8–30 (aHR, 0.79, 95 percent CI, 0.60–1.05). The risk was lower in the nirsevimab group during days 31–60 (aHR, 0.62, 95 percent CI, 0.45–0.84) and beyond 60 days (aHR, 0.51, 95 percent CI, 0.30–0.86).
With regard to the French Deprivation Index, nirsevimab was associated with a lower risk of RSV-associated LRTI hospitalization compared with the RSVpreF vaccine for infants residing in moderately, highly, and most deprived municipalities (quintiles 3, 4, and 5; aHR, 0.66, 95 percent CI, 0.47–0.92). In contrast, the risk did not significantly differ between the two treatment groups for infants living in the least and slightly deprived municipalities (quintiles 1 and 2), with the upper CI limit of the risk estimate being greater than 1 (aHR, 0.81, 95 percent CI, 0.53–1.25).
Secondary outcomes
Results for secondary outcomes also seemed to favour nirsevimab.
Among infants hospitalized for RSV-associated LRTI, those who received nirsevimab were less likely to be admitted to paediatric intensive care unit (0.3 percent vs 0.5 percent; aHR, 0.58, 95 percent CI, 0.42–0.80) and require ventilator support (0.2 percent vs 0.4 percent; aHR, 0.57, 95 percent CI, 0.40–0.81) or oxygen therapy (0.2 percent vs 0.4 percent; aHR, 0.56, 95 percent CI, 0.38–0.81) compared with infants born to mothers vaccinated with the RSVpreF.
Two pathways to protection
The WHO recommends both RSVpreF and nirsevimab for protecting infants against RSV. It advises that maternal RSVpreF be administered to pregnant women during the third trimester, from week 28 onwards, to optimize antibody transfer to their babies. Meanwhile, nirsevimab should be given as a single injection to infants immediately after birth or before discharge from a birthing facility. [https://www.who.int/publications/i/item/who-wer-10022-193-218]
The Global Pediatric Pulmonology Alliance and international expert reviews highlight the two interventions as complementary components of a unified RSV strategy. [Pediatr Pulmonol 2025;60(suppl 1):S120-S122]
Jabagi and colleagues noted that while both RSVpreF and nirsevimab effectively reduce RSV-associated LRTI hospitalizations in infants, the agents differ in immunologic mechanisms and timing of administration.
“Nirsevimab confers passive immunity via a single intramuscular dose at birth, offering direct antibody transfer to the infant regardless of maternal vaccination status or gestational age. It appears to maintain consistent effectiveness over a median follow-up of nearly 4 months, aligning with the duration of an RSV season,” they noted.
“In contrast, maternal RSVpreF vaccination depends on administration within a limited gestational window and on adequate placental antibody transfer. Real-world data on the durability of RSVpreF vaccine–derived infant protection remain limited,” the authors added.
The lower risk of RSV-related LRTI hospitalizations seen in the nirsevimab group beyond 30 and 60 days of follow-up may reflect “potential waning of maternally derived antibodies or insufficient initial antibody levels among some infants in the RSVpreF vaccine group,” they said.
Maternal vaccination advantage
Jabagi and colleagues highlighted some advantages to maternal RSVpreF vaccination.
Importantly, “RSVpreF vaccines generate active immunity against multiple neutralizing epitopes, making immune evasion less likely,” they noted. In contrast, the widespread use of nirsevimab “could theoretically create selective pressure on the virus,” although no significant resistance mutations have been detected yet. [Euro Surveill 2025;30:2400596; Lancet Infect Dis 2025;25:301-311]
The authors also emphasized that the cost of nirsevimab may limit access to the monoclonal antibody in low- and middle-income countries.
Finally, they said administering the RSVpreF vaccine to expectant mothers may be more practical in settings with robust prenatal programmes but limited postnatal follow-up.
The French nationwide cohort
For the study, Jabagi and colleagues used the French National Health Data System. A total of 42,560 infants (mean age 3.7 days, 51.7 percent male, 98.7 percent born at term) born between 1 September and 31 December 2024 who were immunized either with nirsevimab (n=21,280) or via maternal vaccination with RSVpreF (n=21,280) were included. Infants in both immunization groups were matched based on maternity discharge date, sex, gestational age, and region of residence.
Notably, more participants in the nirsevimab group than in the RSVpreF group lived in the most deprived municipalities (French Deprivation Index Q4: 22.2 percent vs 16.7 percent; Q5: 21.7 percent vs 13.8 percent), had complementary solidarity health insurance (20 percent vs 8.7 percent), and used maternal and child community welfare services (6.2 percent vs 4.7 percent).
Serious infections during the birth stay occurred more frequently in the nirsevimab group than in the RSVpreF group (1.8 percent vs 0.8 percent), while the occurrence of congenital anomalies was similar (0.9 percent vs 1 percent). Infants in the nirsevimab group were more likely to be socioeconomically disadvantaged (20 percent vs 8.7 percent).
Most cases of RSV-associated LRTI during the follow-up were bronchiolitis (96.5 percent), and there were few cases of bronchitis or pneumonitis.
The safety of nirsevimab and RSVpreF was not assessed in the study. Jabagi noted that prior evidence indicated a favourable safety profile for nirsevimab in both trials and real-world settings. “In contrast, early trials of the RSVpreF vaccine raised concern about a potential association with preterm birth, but a more recent trial found no difference in overall prematurity rate.” [N Engl J Med 2023;388:1451-1464; N Engl J Med 2023;388:1465-1477; J Infect Dis 2022;225:2056-2066]
Furthermore, data from real-world settings showed no increased risk of preterm birth when RSVpreF vaccination was given within the recommended 32- to 36-week window. [JAMA Netw Open 2025;8:e2460735; Obstet Gynecol 2025;doi:10.1097/AOG.0000000000006121]
The authors acknowledged several study limitations, such as the inclusion of infants born later in the RSV season, follow-up being limited to one RSV season, the lack of data on RSV subtypes, and the potential for unmeasured confounding factors. Additionally, the study was conducted during France’s first season of maternal RSVpreF vaccination, when eligibility was limited to 32–36 weeks of gestation (contrary to the WHO’s recommendation to begin vaccination at 28 weeks of gestation). The subgroup analyses were also not stratified beyond 60 days of follow-up.