Efficacy, Immunogenicity, and Safety of Lipid Nanoparticle-Delivered mRNA Vaccines for Respiratory Syncytial Virus: A Systematic Review & Meta-Analysis
Abstract
Background & Objective: Respiratory syncytial virus (RSV) remains a major burden on global health due to its emerging and re-emerging infections. mRNA vaccines encapsulated in lipid nanoparticles (LNPs) represent a novel platform for RSV prevention. This systematic review and meta-analysis aimed to evaluate the efficacy, immunogenicity, and safety of mRNA-based RSV vaccines compared with placebo in adults aged 18–85 years. Methodology: PubMed, Google Scholar, the Cochrane Library, Web of Science, and ClinicalTrials.gov were searched from inception to August 2025 for randomized controlled trials (RCTs) comparing mRNA vaccines to Placebo. Two reviewers independently screened records, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool. Random-effects meta-analyses were used to estimate pooled treatment effects with 95% confidence intervals (CIs). The review was conducted in accordance with PRISMA guidance and prospectively registered with PROSPERO (CRD420251127043). Results: Seven RCTs (54,898 participants) were included. No difference in serious adverse events was found (RR 1.00, 95% CI 0.89–1.13; P = 0.99; I² = 0%). Solicited adverse events (RR 1.74, 95% CI 1.31–2.32; P < 0.00001) and systemic reactions of any grade (RR 1.22, 95% CI 1.12–1.33; P < 0.00001) were more common with vaccination. Injection-site pain was the most common local reaction (RR 5.64, 95% CI 3.29–9.67; P < 0.00001), and fever was the most pronounced systemic reaction (RR 2.12, 95% CI 1.83–2.44; P < 0.00001). Immunogenicity was analysed narratively due to heterogeneity (I² = 96–98%). In the ConquerRSV subset (n = 1,848; ≥60 years), the approved 50-µg dose produced a geometric mean fold-rise of 8.4 (95% CI 8.0–8.9) for RSV-A and 5.1 (95% CI 4.9–5.4) for RSV-B versus placebo. Conclusion: LNP-encapsulated mRNA vaccines against RSV are safe and generate a good neutralising antibody response in adults, supporting their potential as an effective preventive strategy. Key Words: mRNA Vaccine, Respiratory Syncytial Virus.