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

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, encoding the RSV F-glycoprotein stabilized in the prefusion (preF) conformation and with a deletion at the cytoplasmic tail. mRNA-1345 cell surface protein expression was higher and detected for longer 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 results supported initial clinical evaluation of mRNA-1345 in adults, children, and RSV-naïve infants; mRNA-1345 was recently demonstrated to be efficacious against RSV disease in older adults in a pivotal efficacy study.