Development of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses
Norbert Pardi, Juan Manuel Carreño, George O’Dell, Jessica Tan, Csaba Bajusz, Hiromi Muramatsu, Willemijn F. Rijnink, Shirin Strohmeier, Madhumathi Loganathan, Dominika Bielak, Molly M. H. Sung, Ying K. Tam, Florian Krammer, Meagan McMahon
Abstract
Messenger RNA (mRNA) vaccines represent a new, effective vaccine platform with high capacity for rapid development. Generation of a universal influenza virus vaccine with the potential to elicit long-lasting, broadly cross-reactive immune responses is a necessity for reducing influenza-associated morbidity and mortality. Here we focus on the development of a universal influenza B virus vaccine based on the lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) platform. We evaluate vaccine candidates based on different target antigens that afford protection against challenge with ancestral and recent influenza B viruses from both antigenic lineages. A pentavalent vaccine combining all tested antigens protects mice from morbidity at a very low dose of 50 ng per antigen after a single vaccination. These findings support the further advancement of nucleoside-modified mRNA-LNPs expressing multiple conserved antigens as universal influenza virus vaccine candidates.