Extract from report of GACVS meeting of 12-14 November 2024, published in the WHO Weekly Epidemiological Record on 7 March 2025

The maternal bivalent prefusion F RSV vaccine, RSVPreF (Abrysvo®, Pfizer) is authorized for use in over 40 countries, with various limits on gestational age for its use. The Committees received an overview of safety data obtained from a randomized, placebo-controlled phase-3 clinical trial on the efficacy and safety of Abrysvo®, in which a safety signal related to preterm birth was detected.¹ Although a higher rate of preterm births was observed in the vaccinated group, the increase was not statistically significant. Some geographical variation was seen in the risk for preterm birth in vaccinated groups, with higher relative risks in Argentina and South Africa and a statistically significant difference in South Africa; no imbalance in preterm births was observed between study groups in high-income settings. Data from the South African site of the maternal vaccine trial were used as the basis of a risk– benefit analysis of infant mortality in that country. Although the data used in the model were limited, the results showed that, when the vaccine was given to women at 27–36 weeks gestational age, the benefits were greater than the risk in 98% of simulations. These results were presented to the SAGE at its meeting in September 2024.²

Post-authorization safety data on maternal vaccination with Abrysvo® were also presented. In data from the United States of America (USA) vaccine safety datalink on vaccinated pregnant women during the 2023–2024 season, the rate of preterm births was 4.1%. This is within the expected range of the incidence of preterm births at 32–36 weeks’ gestation³ (3.1–6.1%). In a target trial emulation approach in a cohort study (propensity score matched cohorts), the preterm birth rate was 4.0% among vaccinated women and 4.5% among unvaccinated women (relative risk: 0.90; 95% confidence interval: 0.80, 1.00).

Data received at the Paul-Ehrlich-Institute in Germany and the European Medicines Agency⁴ through the EudraVigilance data analysis system do not currently suggest a safety concern for preterm birth among infants of vaccinated mothers. It should be noted, however, that the information in some case safety reports, particularly regarding preterm births, is probably too limited for conclusive conclusions to be drawn about a potential causal association between vaccination and preterm births because of the limitations of the spontaneous reporting system.

Two RSV vaccines are licensed for older adults: Abrysvo® and the adjuvanted Arexvy® (GSK), which is not indicated for pregnant women. Analysis of all vaccine clinical trials in older adults showed that, within 42 days of vaccination, 3 cases of Guillain-Barré syndrome (GBS) or related inflammatory neurological events were observed with each vaccine.⁵ The Committees considered results of a recent US Food and Drug Administration post-marketing analysis of RSV vaccine safety in a Medicare fee-for-service claims database for beneficiaries aged ≥65 years. Among vaccinations to January 2024, the risk for GBS was increased by 2–3  times after vaccination with the RSV vaccines Abrysvo® and Arexvy® in observed versus expected and self-controlled case series designs. The absolute risk of GBS among recipients of both vaccines was, however, low (fewer than 10 cases per 1 million vaccinees). No difference in GBS risk was found between people who had and had not received concomitant vaccination with RSV vaccines on the same day.

Pfizer has planned 4 non-interventional post-authorization safety studies on maternal vaccination with Abrysvo® – one in the European Union (EU) and 3 in the USA – to address safety concerns related to birth outcomes and GBS, which has not been reported in vaccinated pregnant women to date. The studies will also investigate vaccine safety in certain high-risk groups, such as immunocompromised pregnant women, high-risk pregnancies and immunocompromised or renally or hepatically impaired adults aged ≥60 years. Reports from these 4 studies will be issued periodically between 2024 and the expected final report of the last study in 2032.

The Committees were also informed of plans for a study of the maternal effectiveness and safety of RSV vaccination in 4 African countries to evaluate preterm birth and low birthweight; the study is planned to start in 2025. The Committees discussed the paucity of data from LMICs on maternal vaccination with Abrysvo®, especially in South Asia, where the background rate of preterm birth is high. The Committee stressed the importance of establishing the background rates of preterm birth in a country or other setting, as background rates differ significantly according to site. This information is especially important for analysing observed versus expected rates of preterm birth among pregnant women in the gestational age window for introducing the vaccine. Evidence on co-administration of Abrysvo® with other vaccines was also discussed. The Committees recommended continued monitoring and investigation of adverse events after co-administration of Abrysvo® with other vaccines, the immunogenicity of the co-administered vaccines, such as against influenza and COVID-19, and the occurrence of GBS in pregnant women and the elderly after vaccination. The Committees stressed the importance of studies on maternal RSV vaccination in LMICs, especially in South Asia. The Committees recommended that guidance be provided on collecting data from pregnant women, including vaccination status, to ensure effective safety surveillance without overwhelming health-care professionals. It also recommended focused safety monitoring for higher-risk women, such as those at higher risk of preterm birth or hypertensive disorders (e.g. preeclampsia), including immunocompromised pregnant women, to counteract the selective enrolment of lower risk women into clinical trials.

² See No. 49, 2024, pp. 719–740.

³ US Food and Drug Administration news release. Note: Abrysvo is approved for use at 32–36 weeks gestational age of pregnancy (https://www.fda.gov/news-events/ press-announcements/fda-approves-first-vaccine-pregnant-individuals-prevent-rsv-infants, accessed 6 February 2025).

⁴ European Medicines Agency product information. Note: pregnant women should receive the dose between weeks 24 and 36 of gestation (https://www.ema.europa. eu/en/medicines/human/EPAR/abrysvo#product-info, accessed February 2025).

⁵ Walsh EE et al. RENOIR Clinical Trial Group. Efficacy and safety of a bivalent RSV prefusion F vaccine in older adults. N Engl J Med 2023;388:1465–77. https://doi. org/10.1056/NEJMoa2213836.

Extract from report of GACVS meeting of 15-17 May 2024, published in the WHO Weekly Epidemiological Record on 9 August 2024

Data from a placebo-controlled phase-3 clinical trial on the efficacy and safety of maternal RSV vaccination with Abrysvo® (Pfizer) were presented to the Committee.¹ The participants were pregnant women aged ≤49  years in 18 countries who were at 24–36 weeks of gestation. The  trial was conducted over 4 RSV seasons (2 in the northern hemisphere and 2 in the southern hemisphere), and infants were followed up for 1–2 years for safety and disease end-points. Vaccine efficacy was found to be high in the 7420 women and 7307 infants enrolled in the study and equivalent in high- and low– medium-income countries. The adverse events observed in infants within 1 month of birth were generally similar in the vaccine and placebo groups; while a higher rate of preterm birth was observed in the vaccine group, the increase was not statistically significant. Some geographical variation was seen in the risk for preterm birth in the vaccinated groups, with higher relative risks in Argentina and South Africa, but the difference was not significant in high-income settings.

Abrysvo® has been licensed for use during pregnancy in many countries, although it is being used for maternal vaccination during the current season only in Argentina and the USA. Both the European Medicines Agency and the US Food and Drug Administration require post-marketing studies of the safety of this vaccine during pregnancy and birth. Accordingly, Pfizer is sponsoring studies of vaccinated pregnant women; the US CDC is evaluating its safety at Vaccine Safety Datalink sites; and Argentina plans to monitor the safety of the vaccine during its use in the current RSV season. Once the vaccine is prequalified by WHO, the GACVS expects to review data on post-marketing safety.

GACVS noted that the numerical imbalance in preterm births between study groups is a safety signal, but, given the lack of statistical significance and the absence of a plausible biological mechanism, it should not preclude use of this highly effective vaccine during pregnancy. Post-marketing pharmacovigilance will be important to better understand this safety signal and should be conducted in countries in which the maternal vaccine is used. Owing to low uptake of the vaccine to date, however, it will probably be several years before enough people have been vaccinated for definitive conclusions to be drawn from post-marketing evaluation, including by the company.

¹Kampmann B et al. Bivalent prefusion F vaccine in pregnancy to prevent RSV illness in infants. N Engl J Med. 2023;388(16):1451–64. doi:10.1056/NEJMoa2216480.