168. Safety, Reactogenicity, and Immunogenicity of mRNA-1345, an Investigational Respiratory Syncytial Virus Vaccine, in Participants Aged 2 to &lt; 18 Years at High Risk of Severe Disease
Authors: Schnyder Ghamloush Sabine , Qian Hui , Chen HuiLing , Whitten Joseph , Stoszek Sonia K , Snape Matthew D 
Published: January 2025

Abstract

Background
Respiratory syncytial virus (RSV) is the primary cause of lower respiratory tract disease in children aged &lt; 5 years and causes substantial burden in those at high risk aged 5-18 years. No active RSV vaccine is currently available for children. Here, we present interim safety and immunogenicity of a single injection of the mRNA-based vaccine, mRNA-1345, in participants aged 2 to &lt; 18 years at high risk for severe RSV disease.

Methods
This phase 2, randomized, observer-blind study enrolled participants into 2 age cohorts (2 to &lt; 5 years and 5 to &lt; 18 years). Participants aged 2 to &lt; 5 years were healthy or had stable, chronic conditions increasing risk for RSV disease, and were randomized (1:1:1:1) to receive a single mRNA-1345 injection (7.5, 15, or 30 μg) or placebo. Participants aged 5 to &lt; 18 years had chronic conditions that increased disease risk and were randomized (1:1:1) to receive a single mRNA-1345 injection (15, 30, or 50 μg). Safety and reactogenicity were primary objectives. The secondary objective was immunogenicity, measured by serum RSV neutralizing antibodies (nAb) against RSV-A and RSV-B, and RSV prefusion F (preF)-binding antibodies (bAb). Interim results through Day 29 are reported.

Results
At data cutoff, 162 participants aged 2 to &lt; 5 years (mean 2.9 ± 0.8 years) and 184 participants aged 5 to &lt; 18 years (mean 11.4 ± 3.8 years) had received a vaccination. In both cohorts, solicited adverse reactions were primarily Grade 1-2 in severity; injection site pain, headache, and fatigue were most frequently reported (Figure 1). No deaths occurred and no adverse events (AEs) led to study discontinuation; 1 unrelated serious AE and 1 AE of special interest were reported. At Day 29, a single mRNA-1345 injection increased RSV nAb titers from baseline by 5.9- to 12.7-fold (RSV-A) and 4.3- to 8.9-fold (RSV-B) in those aged 2 to &lt; 5 years, and by 8.2- to 15.8-fold (RSV-A) and 4.7- to 8.0-fold (RSV-B) in those aged 5 to &lt; 18 years (Figure 2). Similarly, vaccination increased RSV preF bAb concentrations at Day 29 for both cohorts (Figure 2).

Conclusion
A single injection of mRNA-1345 was well tolerated, raised no safety concerns, and increased both nAb and bAb immune responses in participants aged 2 to &lt; 18 years. These findings support further development of mRNA-1345 for the pediatric population.

Disclosures
Sabine Schnyder Ghamloush, MD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds (Public Company) Hui Qian, PhD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds (Public Company) HuiLing Chen, PhD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds (Public Company) Joseph Whitten, MD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds (Public Company) Sonia K. Stoszek, PhD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds (Public Company) Matthew D. Snape, MBBS, MD, FRCPCH, FPM, FMedSci, Moderna, Inc.: Emplolyee|Moderna, Inc.: Stocks/Bonds (Public Company)