Direct nirsevimab shot may confer greater infant RSV protection than maternal RSVpreF vax

Administering the monoclonal antibody nirsevimab directly to infants may be more protective than immunization via maternal RSV prefusion F protein (RSVpreF) vaccination, being associated with lower risks of RSV-related hospitalizations and severe outcomes in a real-world setting.

In a population-based cohort study from France, the primary outcome of hospitalization for RSV-associated lower respiratory tract infection (LRTI) occurred less frequently among infants who received nirsevimab vs those born to mothers vaccinated with the 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) over a median follow-up of 84 days. [JAMA 2026;335:787-798]

Infant immunization with nirsevimab reduced the risk of hospitalization for RSV-associated LRTI by 26 percent compared with immunization via maternal RSVpreF vaccination (adjusted hazard ratio [aHR], 0.74, 95 percent confidence interval [CI], 0.61–0.88).

The benefit was observed across subgroups defined by sex, gestational age at birth, and French Deprivation Index.

Severe outcomes mitigated

Results for secondary outcomes also favoured 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) as compared with infants born to mothers vaccinated with the RSVpreF.

Antibody transfer variability

“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,” said 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.

“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,” Jabagi added.

She explained that the lower observed risks with nirsevimab beyond 30 and 60 days of follow-up may reflect potential waning of maternally derived antibodies or insufficient initial antibody levels among some infants immunized via maternal RSVpreF vaccination. However, “this should not be interpreted as evidence against the efficacy of the RSVpreF vaccine.”

Maternal vaccination advantage

There are some advantages to maternal RSVpreF vaccination, Jabagi said.

Importantly, “RSVpreF vaccines generate active immunity against multiple neutralizing epitopes, making immune evasion less likely,” she noted. In contrast, the broad use of nirsevimab “could theoretically create selective pressure on the virus,” although no major resistance mutations have been detected yet. [Euro Surveill 2025;30:2400596; Lancet Infect Dis 2025;25:301-311]

Jabagi added that giving the RSVpreF to expectant mothers may be more practical in settings with strong prenatal programs but limited postnatal follow-up.

In terms of cost, nirsevimab has a higher price than RSVpreF. This may limit access to the monoclonal antibody in low- and middle-income countries, noted Jabagi.

Two pathways to protection

The WHO endorses both RSVpreF and nirsevimab for protecting infants against RSV. It recommends that maternal RSVpreF be given to pregnant women during the third trimester of pregnancy, from week 28 onwards, to optimize for the adequate transfer of antibodies to their baby. Nirsevimab, meanwhile, should be administered as a single injection to infants right 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]

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 two immunization arms were matched based on maternity discharge date, sex, gestational age, and region of residence.

Serious infections during the birth stay were more common in the nirsevimab arm than in the RSVpreF arm (1.8 percent vs 0.8 percent), whereas the frequency of congenital anomalies was similar (0.9 percent vs 1 percent, respectively). Infants in the nirsevimab arm 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]