Influenza neuraminidase as adjuvanted protein or mRNA vaccine protects mice against influenza A and B virus challenge

Abstract Neuraminidase (NA) is an underutilized influenza vaccine antigen despite its recognized contribution to protective immunity. Here, we compared the immunogenicity and protective potential of multiple NA antigens delivered as an adjuvanted recombinant tetrameric protein or as mRNA-LNP encoding full-length NA in naïve mice. Both vaccine types induced robust neuraminidase-inhibiting (NAI) antibody responses and conferred protection to mice challenged with antigenically homologous influenza A or B viruses. However, only immunization with NA-encoding mRNA-LNP protected against challenge with a heterologous HxN2 virus, whereas immunization with recombinant NA was associated with earlier onset of weight loss following heterologous HxN2 virus challenge. Passive transfer of immune serum revealed that protection induced by mRNA immunization can be transferred by serum, and that early onset of weight loss is not induced by recombinant NA-derived sera; on the contrary, partial protection is achieved. Finally, NAI assays against a panel of antigenically distinct HxN2 viruses showed similar breadth of inhibition.