Abstract
Background/Objectives: HIV-exposed uninfected (HEU) infants experience increased severe respiratory syncytial virus lower respiratory tract illness (RSV-LRTI) rates compared with HIV-unexposed infants. Maternal bivalent RSVpreF vaccination can prevent infant RSV-LRTI but data from HEU infants are lacking. Methods: This phase 3 randomized, double-blinded trial assessed RSVpreF safety and immunogenicity in pregnant participants from South Africa living with HIV and their infants. Maternal participants with stable HIV disease taking antiretroviral therapy received RSVpreF or placebo (24-36 weeks' gestation). Primary safety endpoints included reactogenicity through 7 days after vaccination (maternal participants), adverse events (AEs) through 1 month after vaccination (maternal participants) or birth (infants), and serious AEs (SAEs) throughout the study (maternal participants) or through 6 months after birth (infants). Immune responses were evaluated by 50% RSV-A and RSV-B neutralizing titers prevaccination and at delivery (maternal participants) or birth (infants). Results: Overall, 343 maternal participants received RSVpreF (n = 172) or placebo (n = 171). Most reactogenicity events were mild/moderate. AEs and SAEs were generally reported at similar frequencies in maternal RSVpreF and placebo groups including percentages of hypertensive disorders of pregnancy. There were no safety concerns in infants; percentages of reported AEs and SAEs were generally similar between RSVpreF and placebo groups and no difference in preterm birth. RSVpreF elicited high maternal neutralizing RSV-A and RSV-B immune responses, with efficient RSV antibody transplacental transfer to infants demonstrated by levels greater than the placebo group at birth (geometric mean ratios (GMRs) of RSVpreF to placebo were 7.8 for RSV-A and 6.8 for RSV-B) and by comparison with a cohort of HIV-unexposed infants from the pivotal phase 3 efficacy trial (GMRs of HEU to HIV-unexposed infants were 0.86 for RSV-A and 0.72 for RSV-B). Conclusions: These results support maternal RSVpreF vaccination among those living with stable HIV for preventing RSV-LRTI in HEU infants. (NCT06325657).