RSVpreF vaccination in pregnancy: a meta-analysis of maternal-fetal safety and infant efficacy.

Abstract

In May 2023, The United States Food and Drug Administration (FDA) approved a Pfizer©-sponsored (COMPANY, CITY, STATE, COUNTRY) bivalent RSVpreF (respiratory syncytial virus prefusion F protein-based vaccine) RSV vaccine (AbrysvoTM [COMPANY, CITY, STATE, COUNTRY]) for use during pregnancy to prevent neonatal/infant RSV infection. In February of 2022, FDA trials sponsored by GSK© (COMPANY, CITY, STATE, COUNTRY) on a similar RSVpreF RSV vaccine were halted because of the identification of a safety signal related to preterm births. As these vaccines use nearly identical pre-fusion F-protein technology, we sought to synthesize and evaluate the existing high-quality literature on their effectiveness and safety. From inception until March 15, 2024, we searched for randomized controlled trials (RCTs) on this topic. We used Review Manager (RevMan 5.4.1) (COMPANY, CITY, STATE, COUNTRY) to perform the analysis with 95% confidence intervals and risk ratios (RR). Our search yielded three large RCTs. From a safety perspective, many maternal side effects were greater in the RSVpreF group, with an increased incidence of local reactions (RR, 5.98 [3.68, 6.83]; P=0.01; I2=0%), blood disorders (RR, 1.07 [0.69, 1.66]; P=0.78; I2=0%), fatigue (RR, 1.05 [1.00, 1.10]; P=0.07; I2=0%), joint pain (RR, 1.60, 1.39 [0.68, 2.86]; P=0.37; I2=59%), cardiac disorders (RR, 1.19 [0.80, 1.77]; P=0.38; I2=0%), headache (RR, 0.80 [0.30, 2.10]; P=0.65; I2=0%), fever (RR, 0.90 [0.20, 4.16]; P=0.89; I2=57%), gastrointestinal disorders (RR, 1.04 [0.70, 1.56]; P=0.83; I2=0%), and pregnancy complications (RR, 1.01 [0.65, 1.56]; P=0.97; I2=17%). The vaccinated group demonstrated significant reduction RSV-lower respiratory tract disease (LRTD) cases (RR, 0.44 [0.33, 0.57]; P=0.01), severe LRT illness (RR, 0.29 [0.19, 0.44]; P=0.01), and hospitalizations (RR, 0.40 [0.24, 0.67]; P=0.005). RSVpreF vaccination was associated with a higher incidence of preterm delivery (RR, 1.24 [1.08, 1.44]; P=0.03); however, no significant difference in neonatal deaths was observed (RR, 1.42 [0.70, 2.89]; P=0.34). RSVpreF vaccination results in systemic adverse events and an increase in preterm delivery. Vaccination appeared to have acceptable short-term safety for newborns, but did not produce a significant decrease in neonatal death.