Background
Neuraminidase has gained increasing attention as a broadly reactive influenza vaccine antigen capable of mitigating the strain-specific limitations of hemagglutinin-based vaccines.

Methods
We generated an N1 virus-like particle (VLP) vaccine displaying NA from A/Guangdong-Maonan/SWL1536/2019 (H1N1) with M1 from A/California/4/2009 (H1N1), confirmed assembly by western blotting, hemagglutination assay, and transmission electron microscopy, and immunized BALB/c mice intranasally to measure antibody, cellular, and FcγRIV-mediated antibody-dependent cellular cytotoxicity responses.

Results
Intranasal immunization of BALB/c mice with N1-VLPs induced robust neuraminidase-specific IgG responses and markedly increased IgG- and IgA-secreting plasma cells in the lung. Vaccination also enhanced CD4+ and CD8+ T cell responses and expanded germinal center-like B cell populations. Functional antibody activity was demonstrated through FcγRIV-mediated antibody-dependent cellular cytotoxicity assays. Following challenge with B/Malaysia/2506/2004 (Victoria lineage), N1-VLP-immunized mice exhibited minimal weight loss, markedly reduced lung viral titers, and 100% survival, whereas na?ve controls experienced severe disease and high mortality.

Conclusion
These findings indicate that the N1 VLP vaccine induces measurable immune responses, confers protection against heterologous Victoria-lineage influenza B virus challenge in mice, and is well-tolerated.