Development of lipid nanoparticle formulation for intramuscular administration of mRNA vaccine against respiratory syncytial virus

Background: mRNA vaccines have garnered significant attention due to their rapid development and high efficacy, as demonstrated during the COVID-19 pandemic. Respiratory Syncytial Virus (RSV) remains a major cause of respiratory illness, particularly among infants and the elderly, with limited effective vaccine options. This study aimed to develop a lipid nanoparticle (LNP) formulation for an mRNA vaccine targeting the G glycoprotein of RSV. Methods: The LNP formulation was optimized through comprehensive in vitro and in vivo screening. The optimized LNP was used to deliver mRNA encoding the conserved core fragment of RSV G glycoprotein. Immune responses and protective efficacy were evaluated through preclinical studies. Results: The optimized LNP demonstrated superior mRNA expression and stability, inducing high levels of G glycoprotein-specific antibodies and robust T-cell responses. The mRNA/LNP vaccine conferred complete protection against RSV challenge without adverse effects. Conclusions: The mRNA/LNP vaccine targeting the conserved region of the RSV G glycoprotein elicited strong immune responses and demonstrated a favorable safety profile, suggesting its potential as an effective preventive strategy against RSV infection. This study provides valuable insights into the design of LNP-based mRNA vaccines.