An optimized intranasal LNP formulation for potent immune responses of mRNA-based RSV vaccines

and F0). Our optimized intranasal mRNA vaccines encoding RSV antigenic proteins (F4-mRSV and F12-mRSV) exhibit high encapsulation efficiency (∼99%) and stability during storage. Compared with the intranasal F0-mRSV vaccine based on an intramuscular injection formulation, intranasal F4-mRSV and F12-mRSV vaccines induce potent serum RSV-specific IgG and IgA. The intranasal F4-mRSV vaccine induces higher serum-neutralizing antibodies and splenic cellular immunity. Compared with intramuscular vaccination, the intranasal F4-mRSV vaccine induces potent mucosal IgA in the nose and lungs without inducing significant systemic adverse effects. In conclusion, our results suggest that the intranasal F4 LNP formulation is a promising platform for mucosal mRNA vaccines against respiratory viruses.