Safety of the intervention
Following RSV Pre-F vaccination during pregnancy, recipients may experience injection site pain, which is mild to moderate. Systemic symptoms, including muscle pain and headaches may also occur.Go to footnote 1
In clinical trials, serious adverse events included a numerical increase in preterm births in maternal vaccine recipients (this was not statistically significant overall, and available data are insufficient to establish or exclude a causal relationship between preterm birth and the vaccine).Go to footnote 2
A numerical imbalance in preterm births (< 37 weeks gestation) was observed between the groups, occurring in 5.7% of vaccine recipients and 4.7% of placebo recipients (relative-risk [RR]: 1.20; 95% CI: 0.98–1.46).
When the data were stratified by country income levels, the numerical increase in pre-term births was most notable in the two upper-middle-income countries (UMICs), namely Argentina and South Africa.Go to footnote 3
The safety of RSV pre-F vaccine, specifically the risk of excess pre-term births is being further evaluated in the ongoing RSV_IMPACT study in sub-Saharan African settings.Go to footnote 4
Post-authorization safety evaluations in high-income countries and UMICs that have introduced the vaccine have not shown any risk of excess pre-term infants.Go to footnote 5
Unpublished post-marketing data presented to the Global Advisory Committee on Vaccine Safety (GACVS) in June 2026 did not show any excess pre-term births following maternal Pre-F vaccine use in Australia, Argentina, Brazil and the United Kingdom.Go to footnote 6
In a modelling study looking at risk-benefit in South Africa, maternal vaccination was estimated to prevent 31 RSV-associated infant deaths per 100 000 live births, but if the increase in preterm births occurred at the same rate observed in the trial, the model predicted that neonatal deaths related to prematurity could increase by 44 per 100 000 births when vaccination occurred between 24–36 weeks of gestation. However, if vaccination was limited to 27–36 weeks gestation, the predicted risks were substantially lower, and in 97% of simulations the benefits outweighed the risks. Overall, the findings suggest that third-trimester RSV Pre-F vaccination may provide a more favourable benefit-risk balance.Go to footnote 7
Since the risk of pre-term births was mainly observed at two upper-middle-income country sites and data were very sparse from low- and low-middle-income countries, a trial that is powered to detect the risk of excess pre-term births has been initiated in four sub-Saharan African countries (the IMPACT study).Go to footnote 4
In postmarketing safety surveillance in Spain, the common adverse events reported following the administration of nirsevimab included maculo-papular and papular rash, and injection site pain, induration, oedema and swelling. The rate of serious adverse events was 23.1/ 100 000 doses administered. No antibody-dependent enhancement or other unexpected risks were reported.Go to footnote 8
In healthy pre-term and term infants, serious adverse events were reported in 278 of 2 409 infants (11.5%) in the clesrovimab group and 149 of 1 202 infants (12.4%) in the placebo group.Go to footnote 9 In children at high risk for severe RSV disease entering their second RSV season, a 210 mg dose of clesrovimab was well tolerated.Go to footnote 10
- Go back to footnote reference 1
FDA-Approved drugs (2024). United States Food and Drug Administration (FDA) (https://www.fda.gov/media/168889/download?attachment, accessed 28 June 2026).
- Go back to footnote reference 2
WHO position paper on immunization to protect infants against respiratory syncytial virus disease, May 2025 Weekly Epidemiological Record. 2025;100(22):193-218 ( https://www.who.int/publications/i/item/WER10022t, accessed 22 September 2026).
- Go back to footnote reference 3
Background paper: Long-acting monoclonal antibodies and maternal RSV vaccine for prevention of severe Respiratory Syncytial Virus (RSV) disease in infants . World Health Organization; 2024 (https://terrance.who.int/mediacentre/data/sage/SAGE_eYB_Sept2024.pdf, accessed 22 September 2026).
- Go back to footnote reference 4
RSV_IMPACT Study: Maternal RSV Vaccination to Protect Infants. University of Witwatersrand; 2025 (https://wrhi.ac.za/projects/rsv_impact-study/, accessed 22 September 2026).
- Go back to footnote reference 5
DeSilva M (2024). RSVpreF vaccine, preterm birth, and small for gestational age at birth: preliminary results from the Vaccine Safety Datalink. ACIP meeting, October 2024 (https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/03-RSV-Mat-Peds-DeSilva-508.pdf, accessed 28 June 2026).
- Go back to footnote reference 6
Report of the joint meeting of ACSoMP and GACVS, June 2026. Weekly Epidemiological Record. 2026;101(34):187–192 (https://www.who.int/publications/journals/weekly-epidemiological-record/wer101-34, accessed 23 September 2026).
- Go back to footnote reference 7
Monoi A, Endo A, Procter SR, Leuba SI, Flasche S, et al. (2026) The benefits and risks of maternal RSV vaccination on mortality in South Africa: A modeling study. PLOS Medicine 23(1): e1004625. doi:10.1371/journal.pmed.1004625.
- Go back to footnote reference 8
Estrella-Porter P, Correcher-Martínez E, Orrico-Sánchez A, Carreras JJ. Post-Marketing Surveillance of Nirsevimab: Safety Profile and Adverse Event Analysis from Spain's 2023-2024 RSV Immunisation Campaign. Vaccines (Basel). 2025 Jun 10;13(6):623. doi:10.3390/vaccines13060623.
- Go back to footnote reference 9
Zar HJ, Simoes EAF, Madhi SA, Ramilo O, Senders SD, et al. Clesrovimab for Prevention of RSV Disease in Healthy Infants. N Engl J Med. 2025;393(13):1292-303. doi:10.1056/NEJMoa2502984.
- Go back to footnote reference 10
Zar HJ, Bont LJ, Manzoni P, Munoz FM, Ramilo O, et al. Clesrovimab in Infants at Increased Risk For Severe Disease During 2 RSV Seasons: A Randomized Clinical Trial. JAMA Pediatr. 2026. doi:10.1001/jamapediatrics.2026.2760.