Nirsevimab's RSV Protection Fades by Second Year

A nationwide cohort study published in JAMA Pediatrics found that nirsevimab (Beyfortus), a monoclonal antibody used to prevent respiratory syncytial virus (RSV) disease in infants, maintained strong effectiveness against RSV-LRTI–related hospitalization across 2 consecutive French immunization campaigns but showed no protective association during a second year of follow-up. The study found higher rates of hospitalization for ear, nose, and throat (ENT) bacterial infections and asthma among immunized infants.¹

Investigators analyzed 2 nationwide matched cohorts using the French National Health Data System (SNDS), following infants born in metropolitan France before the 2023 and 2024 nirsevimab immunization campaigns. Infants who received nirsevimab were matched 1:1 to unimmunized infants based on sex, birth month, gestational age, department of residence, and social deprivation index. The 2023 cohort included 74,672 infants, and the 2024 cohort included 175,526 infants. Both cohorts were followed for 1 year, with the 2023 cohort followed for an additional second year.¹

First-Year Effectiveness Held Steady Across 2 Seasons With Different RSV Strains

During the first year of follow-up, RSV-LRTI-related hospitalizations occurred in 0.8% of immunized versus 2.4% of unimmunized infants in the 2023 cohort and in 0.5% versus 1.9%, respectively, in the 2024 cohort. This translated to effectiveness estimates of 66% (95% CI, 61%-70%) in 2023-2024 and 72% (95% CI, 69%-75%) in 2024-2025.¹

The consistency across seasons was notable given that RSV A predominated during the 2023-2024 introduction season, and RSV B predominated during 2024-2025, alongside the emergence of RSV B variants carrying resistance-associated mutations. The researchers noted this stability was reassuring given the change in circulating RSV type and the sharp rise in the proportion of infants immunized, from about 13% in 2023-2024 to about 47% in 2024-2025.¹

In the 2024 cohort, the protective association was stronger among infants aged 3 months or younger (weighted hazard ratio [wHR], 0.22; 95% CI, 0.18-0.26) compared with those older than 3 months (wHR, 0.34; 95% CI, 0.30-0.39).¹

No Protection Seen in Second Year, With Signals for ENT Infections and Asthma

During the second year of follow-up in the 2023 cohort, RSV-LRTI-related hospitalizations occurred in 0.2% of both immunized and unimmunized infants, with no significant protective association observed (wHR, 1.03; 95% CI, 0.73-1.43). The authors noted this finding is biologically plausible given that nirsevimab provides passive immunity for approximately 5 months, corresponding to a single RSV season.¹

Across both years of follow-up, nirsevimab exposure was associated with higher rates of hospitalization for ENT bacterial infections, primarily acute otitis media. In the first year, this association held in both the 2023 cohort (wHR, 1.36; 95% CI, 1.00-1.84) and the 2024 cohort (wHR, 1.43; 95% CI, 1.15-1.78). During the second year, the association strengthened further (wHR, 1.56; 95% CI, 1.10-2.22). An association with higher rates of asthma hospitalization also emerged during the second year (wHR, 1.24; 95% CI, 1.05-1.46), though no such association was seen in either cohort's first year.¹

The study authors offered several possible explanations for the asthma signal, including a rebound effect after first-year protection, reduced natural immune priming during the period of passive antibody protection, and the established link between viral respiratory infections and asthma exacerbations at this age. However, they cautioned that these hypotheses "remain challenging and speculative" and that asthma diagnoses before age 2 years can be difficult to interpret, since early wheezing episodes do not always reflect persistent asthma.¹

Importantly, the authors emphasized that the ENT and asthma associations were based on a comparatively small number of events and should be weighed against the substantial reduction in RSV-LRTI-related hospitalizations achieved during the first year.¹

What This Means for Pharmacists

Nirsevimab (Beyfortus) is administered as a single intramuscular injection, typically given by or under the supervision of a physician shortly before or during RSV season, which generally runs from October through the end of March in most of the continental United States.^2,3

Pharmacists counseling caregivers on immunization schedules should be aware that current dosing calls for only 1 dose per season and that infants and young children at increased risk for severe RSV disease entering a second RSV season may require a separate, higher dose.³

The new French data reinforce that nirsevimab's protective window is tied to its pharmacokinetic half-life rather than lasting immunity, a distinction that matters for counseling families of infants approaching their second RSV season. The findings on ENT infections and asthma, while modest in magnitude, may prompt questions from parents. Pharmacists can point to the study's own caveats about small event numbers and remind families that the drug's core benefit—a substantial reduction in RSV hospitalization risk during the first year—remains well established across multiple studies, including the original randomized MELODY trial.⁴

Pharmacists should also remain familiar with nirsevimab's known adverse effect profile, including injection-site reactions and, in the MELODY trial, a case of nirsevimab-related generalized macular rash; serious hypersensitivity reactions, including anaphylaxis, have been described with other human IgG1 monoclonal antibodies and warrant caution in infants with bleeding disorders.^2,4

The FDA approved nirsevimab (Beyfortus, AstraZeneca) in July 2023 for the prevention of RSV lower respiratory tract disease in neonates and infants born during or entering their first RSV season and in children up to 24 months of age who remain vulnerable through their second RSV season. The approval was supported by 3 clinical trials. In the pivotal MELODY trial of term and late-preterm infants, nirsevimab reduced the risk of medically attended RSV-associated LRTI by approximately 75% relative to placebo (12 of 994 infants receiving nirsevimab experienced the outcome, compared with 25 of 496 infants receiving placebo).^3,4

REFERENCES

1. Gabet A, Kolla E, Tréluyer L, et al. First- and Second-Year Outcomes After Nirsevimab Immunization. JAMA Pediatr. Published online August 10, 2026. doi:10.1001/jamapediatrics.2026.3384

2. Jones JM, Fleming-Dutra KE, Prill MM, et al. Use of nirsevimab for the prevention of respiratory syncytial virus disease among infants and young children: recommendations of the Advisory Committee on Immunization Practices — United States, 2023. MMWR Morb Mortal Wkly Rep. 2023;72(34):920-925. doi:10.15585/mmwr.mm7234a4

3. FDA approves new drug to prevent RSV in babies and toddlers. News release. US Food and Drug Administration. July 17, 2023. Accessed August 11, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-prevent-rsv-babies-and-toddlers

4. Hammitt LL, Dagan R, Yuan Y, et al. Nirsevimab for Prevention of RSV in Healthy Late-Preterm and Term Infants. N Engl J Med. 2022;386(9):837-846. doi:10.1056/NEJMoa2110275