Capsid virus-like particle display improves recombinant influenza neuraminidase antigen stability and immunogenicity in mice

Highlights•cVLP-display increases rNA immunogenicity and reduces the protective dose•Coupling to cVLPs stabilizes and maintains rNA potency for at least 10 months at 4°C•cVLP-displayed rNA can be co-administered with commercial HA-based influenza vaccinesSummarySupplementing influenza vaccines with additional protective antigens such as neuraminidase (NA) is a promising strategy for increasing the breadth of the immune response. Here, we improved the immunogenicity and stability of secreted recombinant NA (rNA) tetramers by covalently conjugating them onto the surface of AP205 capsid virus-like particles (cVLPs) using a Tag/Catcher ligation system. cVLP display increased the induction of IgG2a subclass anti-NA antibodies, which exhibited cross-reactivity with an antigenically distant homologous NA. It also reduced the single dose rNA amounts needed for protection against viral challenge in mice, demonstrating a dose-sparing effect. Moreover, effective cVLP-display was achieved across different NA subtypes, even when the conjugation was performed shortly before administration. Notably, the rNA-cVLP immunogenicity was retained upon mixing or co-administering with commercial vaccines. These results highlight the potential of this approach for bolstering the protective immune responses elicited by influenza vaccines.Graphical abstract