Characteristics of neuraminidase-specific immune responses in influenza vaccinated or naturally infected populations in Shenzhen, China

<p><strong>INTRODUCTION: </strong>Neuraminidase (NA) is a promising target for developing a broadly cross-reactive influenza vaccine. However, NA-specific immune responses in vaccinated or naturally infected populations are not fully understood, which is essential for guiding the design of an NA-based influenza vaccine.</p><p><strong>METHODS: </strong>H1N1 and H3N2 patients were recruited from Shenzhen clinics (March-November 2023), along with vaccinated healthy individuals. NA-specific humoral and cellular immune responses were assessed using ELISA, ELISpot, and Bio-Plex Multiplex Immunoassay, and statistically analyzed.</p><p><strong>RESULTS: </strong>This study included 101 vaccinated healthy individuals, 87 H1N1 patients, and 45 H3N2 patients. IgG antibody titers against HA, NA1, and NA2 were monitored in influenza patients (acute/convalescent phases) and vaccinated individuals (pre/post-vaccination). HA antibody levels in H1N1 patients and NA2 antibody levels in H3N2 patients during the acute phase were lower than those in healthy individuals. In vaccinated individuals, HA antibody and NA2 antibody titers increased post-immunization, except in those &gt;50 years old. Both natural infection and vaccination elicited NA2 antibodies, with higher levels in naturally infected individuals. NA-specific T-cell responses were observed in both groups. Cytokine analysis revealed increased inflammation following infection but stable levels following vaccination.</p><p><strong>CONCLUSION: </strong>NA-specific humoral and cellular immune responses were effectively elicited by both influenza vaccination and natural infection, though with differential reactivity to NA1 versus NA2. Natural infection induced significantly stronger NA-specific responses and transient inflammation when compared with influenza vaccination. These findings contribute to a deeper understanding of NA-specific immune responses, thus providing insights for enhancing the immunogenicity of next-generation NA-based influenza vaccines.</p>