Literature
Clinical Pearls & Morning Reports
Published April 19, 2023
How effective was the RSVpreF vaccine in protecting infants against RSV-associated lower respiratory tract illness in the trial by Kampmann et al.?
Whether maternal vaccination during pregnancy can reduce the burden of respiratory syncytial virus (RSV)–associated lower respiratory tract illness in newborns and infants is uncertain. Kampmann et al. recently reported the results of a phase 3 trial evaluating the efficacy and safety of maternal RSVpreF vaccination in preventing RSV-associated lower respiratory tract illness in infants. Read the NEJM Original Article here.
Clinical Pearls
Q: At what age does severe RSV-associated lower respiratory tract illness peak in infants?
A: RSV is the most common cause of acute lower respiratory tract illness and a leading cause of death in infants younger than 6 months of age, particularly in low- and middle-income countries. Severe RSV-associated lower respiratory tract illness peaks in the first 2 to 3 months of life, despite the presence of naturally acquired maternal antibodies. In a recent European study, approximately 50% of hospitalizations for respiratory tract illness in children younger than 1 year of age were associated with RSV, and approximately 60% of these illnesses occurred in infants younger than 3 months of age.
Q: Are there currently any licensed RSV vaccines?
A: Despite more than 50 years of development efforts, no RSV vaccine has been licensed. The prefusion form (preF) of the RSV fusion (F) glycoprotein is a major target of potent virus neutralizing antibodies and a key vaccine antigen. The investigational bivalent RSVpreF vaccine contains stabilized preF glycoproteins from the two main cocirculating antigenic subgroups (RSV A and RSV B). In a phase 2b, proof-of-concept trial, RSVpreF vaccine administered to women in the late second or third trimester of pregnancy had an acceptable safety profile and elicited neutralizing antibody responses that were efficiently transferred to infants.
Morning Report Questions
Q: How effective was the RSVpreF vaccine in protecting infants against RSV-associated lower respiratory tract illness in the trial by Kampmann et al.?
A: In this worldwide, phase 3 trial, maternal vaccination with RSVpreF was efficacious in preventing medically attended severe RSV-associated lower respiratory tract illness in infants, with vaccine efficacy of 81.8% (99.5% CI, 40.6 to 96.3) within 90 days after birth and 69.4% (97.58% CI, 44.3 to 84.1) within 180 days after birth. For the second primary end point of medically attended RSV-associated lower respiratory tract illness within 90 days after birth, the criterion for vaccine efficacy was not met. The safety and side-effect profile of RSVpreF vaccine in maternal participants were consistent with those in previous phase 1–2 clinical studies involving adults, with mostly mild-to-moderate reactogenicity and adverse-event and serious-adverse-event profiles that were similar to those of placebo. It is reassuring that no safety concerns were detected in the infants or mothers in this trial, although the number of participants was small.
Q: Describe some of the limitations of the trial.
A: One limitation of the trial was the exclusion of women with high-risk pregnancies such as those with a current risk of preterm birth, multiple pregnancy, or a previous infant with a clinically significant congenital anomaly. Offspring of these women could be at higher risk for severe RSV-associated illness. Further limitations of the trial include limited data from low-income countries where the vaccine is likely to have the greatest effect. In addition, the trial was insufficiently powered to assess differences in vaccine efficacy according to RSV antigen subgroup.