Design and preclinical assessment of mRNA-1345 prefusion F glycoprotein-encoding mRNA vaccine for respiratory syncytial virus

Abstract Respiratory syncytial virus (RSV) is a significant cause of lower respiratory tract disease in young children and older adults. We designed a codon optimized mRNA vaccine, mRNA-1345, that encodes the RSV F-glycoprotein stabilized in the prefusion (preF) conformation and with a deletion at the cytoplasmic tail. mRNA-1345 protein expression was higher in vitro versus previous mRNA-based RSV vaccine candidates evaluated clinically. In rodent models, mRNA-1345 induced a robust neutralizing and preF-biased antibody response, a T helper 1-biased cellular response, and demonstrated dose-dependent protection against RSV challenge with no evidence of enhanced respiratory disease. These findings underscored the potential of mRNA-1345 as an effective RSV vaccine and are substantiated by clinical data demonstrating efficacy of mRNA-1345 in older adults.