Nirsevimab and clesrovimab both reduce respiratory syncytial virus (RSV) disease in infants, according to the phase 3 MELODY and phase 2b-3 CLEVER trials published in The New England Journal of Medicine. The studies tested the antibodies separately rather than head to head, so their efficacy percentages cannot be used to rank one above the other, while current CDC guidance distinguishes them most clearly by first-season dosing and second-season eligibility.
Both antibodies target the RSV fusion protein but bind different epitopes
Respiratory syncytial virus enters respiratory cells using its fusion (F) protein. Nirsevimab and clesrovimab both neutralize RSV by binding that protein and blocking membrane fusion, but they recognize different epitopes.
Nirsevimab binds antigenic site Ø on the prefusion form of the F protein. Clesrovimab binds site IV, which is present on both prefusion and postfusion conformations. In the phase 2b-3 CLEVER trial, investigators noted that site IV was highly conserved across RSV A and B sequences, which is one reason it was attractive as a preventive target.
The two products also use Fc modifications that extend antibody persistence, allowing protection across a typical RSV season after one injection. This is passive immunization: the infant receives the antibody directly rather than generating it after vaccination. Our earlier maternal RSV vaccine versus nirsevimab comparison explains that distinction in more detail.
Nirsevimab showed strong efficacy across multiple infant trial populations
The phase 3 MELODY trial randomized 1,490 healthy infants born at 35 weeks’ gestation or later in a 2:1 ratio to nirsevimab or placebo before RSV season. The primary endpoint was medically attended RSV-associated lower respiratory tract infection through 150 days.
The endpoint occurred in 12 of 994 infants assigned to nirsevimab and 25 of 496 assigned to placebo, corresponding to 74.5% efficacy (95% confidence interval, 49.6 to 87.1; P<0.001). Hospitalization for RSV-associated lower respiratory tract infection occurred in 6 versus 8 infants, for an estimated efficacy of 62.1%, but that comparison was not statistically significant in the original MELODY analysis.
An earlier phase 2b trial in 1,453 preterm infants found a 70.1% reduction in medically attended RSV lower respiratory tract infection and a 78.4% reduction in RSV-associated hospitalization through 150 days. Those trials supported the original U.S. approval of nirsevimab for prevention of RSV lower respiratory tract disease in 2023.
Clesrovimab reduced both medically attended illness and hospitalization in CLEVER
Clesrovimab received FDA approval in June 2025. The pivotal CLEVER trial enrolled healthy preterm and full-term infants entering their first RSV season and randomized them 2:1 to a single 105 mg intramuscular dose of clesrovimab or placebo.
A total of 3,614 infants received study treatment: 2,412 received clesrovimab and 1,202 received placebo. Through day 150, RSV-associated medically attended lower respiratory infection occurred in 60 of 2,398 evaluable infants in the clesrovimab group and 74 of 1,201 in the placebo group. That corresponded to 60.4% efficacy (95% confidence interval, 44.1 to 71.9; P<0.001).
RSV-associated hospitalization occurred in 9 of 2,398 infants receiving clesrovimab and 28 of 1,201 receiving placebo, corresponding to 84.2% efficacy (95% confidence interval, 66.6 to 92.6; P<0.001). Serious adverse events were reported in 11.5% of clesrovimab recipients and 12.4% of placebo recipients.
The CLEVER trial was funded by Merck Sharp & Dohme, the manufacturer of clesrovimab. MELODY was funded by MedImmune/AstraZeneca and Sanofi. The CLEVER investigators concluded that a single 105 mg dose “provided protection against mild, moderate, and severe RSV disease” in healthy preterm and full-term infants.
The efficacy percentages do not establish that one antibody is better
The nirsevimab and clesrovimab trials were conducted in different years, enrolled different populations, and were not designed as a direct comparison. Even when primary endpoints sound similar, trial conduct, baseline risk, RSV circulation, geography, and hospitalization practices can change the observed event rates.
That is why it would be misleading to conclude that nirsevimab is better because one medically attended illness percentage is higher, or that clesrovimab is better because one hospitalization percentage is higher. A head-to-head randomized trial would be needed to determine comparative efficacy directly.
CDC also reports pooled efficacy estimates across nirsevimab trials that differ from the original MELODY numbers, further illustrating why a single percentage should not be treated as a universal product ranking.
Dosing is one of the clearest practical differences
For infants born during or entering their first RSV season, nirsevimab dosing depends on body weight. The FDA-recommended dose is 50 mg for infants weighing less than 5 kg and 100 mg for those weighing at least 5 kg.
Clesrovimab uses a fixed 105 mg intramuscular dose for eligible neonates and infants entering their first RSV season, regardless of weight. CDC’s 2025 recommendations specifically note this distinction.
Nirsevimab also has an additional role beyond the first season. It is recommended for certain children 8 through 19 months of age who remain at increased risk for severe RSV disease during their second RSV season. The second-season nirsevimab dose is 200 mg. Clesrovimab is not currently recommended for that second-season high-risk group.
CDC recommends either long-acting antibody for eligible infants in the first season
For most infants younger than 8 months entering their first RSV season, CDC recommends an infant RSV antibody if the mother did not receive maternal RSV vaccine during pregnancy, the maternal vaccination status is unknown, or the infant was born within 14 days after maternal vaccination.
In that setting, either nirsevimab or clesrovimab can be used. CDC does not recommend routinely giving both products to the same infant. The goal is seasonal protection with one long-acting monoclonal antibody when infant immunization is indicated.
This passive-antibody strategy is biologically different from vaccination. Vaccines ask the recipient’s immune system to generate its own adaptive response, whereas monoclonal antibodies provide ready-made neutralizing proteins. Our explainer on how mRNA vaccines generate immunity shows the contrast between active vaccination and passive antibody protection.
What the evidence cannot yet answer
There is no randomized head-to-head trial establishing whether nirsevimab or clesrovimab provides better protection in otherwise similar infants. Real-world effectiveness data are also much more mature for nirsevimab because it entered U.S. practice earlier.
Resistance surveillance will remain important because the antibodies bind different sites on the RSV F protein. In theory, targeting different epitopes could affect vulnerability to viral escape, but current clinical data do not show that this makes one product categorically superior.
The practical choice may therefore depend less on an assumed efficacy ranking and more on age, RSV season, body weight, second-season eligibility, local product availability, and clinician judgment.
The two products broaden infant RSV prevention without making the decision more complicated than it needs to be
For the first RSV season, nirsevimab and clesrovimab are both evidence-based long-acting antibody options. Nirsevimab has weight-based first-season dosing and an established role for selected high-risk children in a second season, while clesrovimab offers a single fixed 105 mg first-season dose. The available trials show that both reduce clinically important RSV disease, but they do not provide a scientific basis for declaring one universally better than the other.
References
- 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;386:837-846. DOI: 10.1056/NEJMoa2110275.
- Zar HJ, Simões EAF, Madhi SA, et al. Clesrovimab for Prevention of RSV Disease in Healthy Infants. N Engl J Med. 2025;393:1292-1303. DOI: 10.1056/NEJMoa2502984.