Design and preclinical assessment of mRNA-1345 prefusion F glycoprotein-encoding mRNA vaccine for respiratory syncytial virus
Christine A. Shaw, Guillaume B. E. Stewart-Jones, Patricia A. Jorquera, Elisabeth Narayanan, Sayda M. Elbashir, Paulina Kapłonek, LingZhi Ma, Naila Hunter, Erin Hanahoe, Tatiana Ketova, Cosmin Mihai, Sachin Mani, Edison Ong, Vladimir Presnyak, Amy E. Rabideau, David W. Reid, Angela Woods, Andrea Carfı́
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, 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.