Research Summary

mRNA RSV Vaccine Safe and Immunogenic in Seropositive Children Aged 12–59 Months

Miranda Manier, BA

Key Highlights

  • An mRNA respiratory syncytial virus (RSV) vaccine was well tolerated in children aged 12–59 months who were seropositive for RSV.
  • No serious adverse events, deaths, or study discontinuations were reported during 12 months of follow-up.
  • A single injection increased RSV-A and RSV-B neutralizing antibodies, as well as prefusion and postfusion binding antibody concentrations.
  • Subsequent doses did not further increase antibody responses, which were biased toward the prefusion conformation.

A phase 1, randomized, observer-blind study evaluated the safety and immunogenicity of an mRNA respiratory syncytial virus (RSV) vaccine encoding the prefusion (preF) stabilized F glycoprotein in RSV-seropositive children aged 12–59 months. The vaccine was well tolerated at both 15 μg and 30 μg dose levels, and a single injection boosted neutralizing and binding antibody responses without any serious safety concerns.

RSV is a leading cause of lower respiratory tract infection in children aged 5 years or younger, and reinfection remains common despite early exposure. Although passive prophylaxis is available, active pediatric vaccination has long been limited due to past concerns about vaccine-associated enhanced disease. Improved understanding of RSV antigens, specifically stabilization of the F glycoprotein in the prefusion form, has enabled new vaccine approaches. This study addressed the need to evaluate the safety and immunogenicity of an mRNA RSV vaccine in children with evidence of prior RSV infection.

This randomized, observer-blind, phase 1 study enrolled 46 RSV-seropositive children aged 12–59 months. Participants were assigned to receive three doses of the mRNA RSV vaccine at 15 μg or 30 μg, or placebo, each dose administered 56 days apart. Safety was monitored over 12 months, and immunogenicity was assessed by neutralizing antibody titers against RSV-A and RSV-B and binding antibody concentrations against prefusion and postfusion RSV F proteins.

The vaccine was well tolerated at both dose levels. The most common local reaction was injection site tenderness, and the most frequent systemic reactions were irritability or crying, loss of appetite, and sleepiness. Most adverse reactions were grade 1 or 2. A single case of grade 4 fever occurred after the first 30 μg injection, leading to a temporary study pause, but the participant recovered without medical intervention and completed the study. Importantly, no serious adverse events, deaths, adverse events of special interest, or events leading to study discontinuation were reported. Three medically attended RSV infections occurred, all among placebo recipients.

A single injection of the vaccine substantially boosted antibody responses. At 1 month, geometric mean fold rises from baseline for RSV-A neutralizing antibodies were 18.9 with the 15 μg dose and 34.9 with the 30 μg dose, while RSV-B neutralizing antibody rises were 7.2 and 14.3, respectively. Binding antibody concentrations also increased, with responses biased toward the prefusion conformation. Additional doses did not further enhance antibody responses, indicating the potential effectiveness of a single injection in this population.

The study is limited by its small sample size and lack of assessment of antibody durability beyond the measured follow-up period.

 “mRNA-1345 was well tolerated and boosted antibody levels in seropositive children aged 12–59 months,” Schnyder and colleagues concluded.

Reference
Schnyder Ghamloush S, Fanning S, et al. Safety and immunogenicity of an mRNA-based RSV vaccine in seropositive children aged 12-59 months. Hum Vaccin Immunother. 2025;21(1):2557676. doi:10.1080/21645515.2025.2557676