Prefusion-stabilized F glycoprotein RSV vaccine reduced incidence of lower respiratory tract illness in infants when given to their mothers during pregnancy, and in older adults.

Respiratory syncytial virus (RSV) infections cause significant morbidity in infants and elders. In two industry-sponsored studies, efficacy of a bivalent prefusion-stabilized F glycoprotein RSV vaccine was evaluated in pregnant women (to prevent disease in their infants) and in older adults.

In the MATISSE study, investigators randomized 7358 pregnant women (median 31.3 weeks’ gestation) to receive vaccine or placebo, then performed disease surveillance in their infants for 12–24 months to assess prevention of medically attended severe RSV-associated lower respiratory tract illness (LRTI) and medically attended RSV-associated LRTI in infants within 180 days of birth (the primary endpoints). Vaccine efficacy (VE) at preventing medically attended severe RSV-associated LRTI was 81.8% at 90 days and 69.4% at 180 days, while VE at preventing medically attended RSV-associated LRTI did not meet prespecified success criteria (57.1% [90 days] and 51.3% [180 days]). Injection-site reactions were more common in the vaccine group (41% vs. 10%) but most systemic reactions were comparable between groups, as was incidence of premature delivery. Four serious adverse events in the vaccine group and one in the placebo group were deemed related to study product.

In the RENOIR study, investigators randomized 34,284 older adults (median age, 67; congestive heart failure, 1.8%; chronic obstructive pulmonary disease, 6.1%) to receive vaccine or placebo. The two primary endpoints were prevention of RSV-associated LRTI with 2 symptoms or with 3 symptoms. At data cutoff, 11 cases of RSV-associated LRTI with 2 symptoms had occurred in the vaccine group and 33 in the placebo group, for a VE of 66.7%; and 2 cases of RSV-associated LRTI with 3 symptoms occurred in the vaccine group and 14 in the placebo group, for a VE of 85.7%. Local reactions were more likely in the vaccine group than the placebo group (12% vs. 7%), but incidence of systemic reactions was similar between groups. Three serious adverse events related to study product occurred in the vaccine group: 1 case each of Guillain-Barré syndrome, Miller-Fisher syndrome, and delayed allergic reaction.

Comment

Administering an RSV vaccine to pregnant women to protect their infants echoes similar approaches against pertussis, tetanus, and influenza. Regarding study limitations, in MATISSE, women with certain high-risk pregnancies were excluded — and in RENOIR, elders at high risk for RSV-associated complications were not well represented. For both studies, surveillance was conducted during the COVID-19 pandemic with its attendant disruption of typical RSV circulation patterns. These interim safety findings (especially in RENOIR) signal the need for close follow-up and intensive post-marketing surveillance, should the vaccine achieve approval and recommendation in the specified populations. An AS01E-adjuvanted prefusion-stabilized F glycoprotein vaccine. opens in new tab was recently approved by the FDA for the prevention of LRTI in persons aged ≥60 years. Regulatory authorities are now evaluating the safety and efficacy of the present unadjuvanted vaccine.