Respiratory syncytial virus mRNA vaccine-induced immunity and protection against subgroups A and B in mice.

Respiratory syncytial virus (RSV) is a major global cause of severe lower respiratory tract infections in infants and older adults. RSV has 2 subgroups, A (RSV-A) and B (RSV-B), which circulate together with different patterns of dominance. A vaccine must protect against both. Reccently, prefusion F protein-based vaccines for maternal and older adult populations achieved ∼70% efficacy, and Moderna's mRNA vaccine for older adults further underscores the potential of mRNA platforms. Here, we report preclinical evaluation of VER-027, a novel mRNA vaccine encoding prefusion F proteins from both RSV-A and RSV-B. A 2-dose intramuscular regimen induced high pre-F-specific immunoglobulin G (IgG) titers, potent neutralizing activity against both subgroups, and robust F85-93-specific CD8+ T cell responses. All mice vaccinated with this mRNA vaccine were fully protected against RSV-A and RSV-B challenge. These findings support VER-027 as a strong candidate for clinical development as a dual-subgroup RSV vaccine.