Fig. 1: Intranasal administration of QIV in combination with NVT provides superior protection against homologous influenza virus challenge.

a Experimental design. BALB/c mice (n = 15 per group) were immunized i.m. with QIV or i.n. with QIV or QIV + NVT twice at two-week intervals. Two weeks after the last immunization, immune response analysis (n = 5 per group) (b–d) and H1N1 virus (A/Korea/2785/2009) challenge (n = 10 per group) (e, f) were performed. Schematic image was created in BioRender. Han, S. (2024) BioRender.com/d59a368. b, c (b) QIV-specific total IgG, IgG1, and IgG2a in the serum and (c) QIV-specific IgA in the nasal wash and BALF were assessed via ELISA. The data are expressed as dot plots, with horizontal lines representing the medians. d After stimulating lung and spleen cells with QIV, the IFN-γ⁺CD4⁺ T-cell response was determined by flow cytometry. Box and whisker plots show the median (center), 25th and 75th percentiles (box), and lowest and highest values (whiskers). e, f The vaccinated mice were infected i.n. with (e) 100 LD₅₀ (n = 5 per group) or (f) 5000 LD₅₀ (n = 5 per group) of H1N1 virus, and body weight and survival were monitored daily. Weight-loss data are shown as mean value ± standard deviation (SD). Survival data are represented as Kaplan‒Meier survival curves, and the significant differences in survival rates were calculated by the log-rank test. b-f Statistical analyses were performed using one-way ANOVA with Tukey’s multiple comparisons test or two-sided Mann–Whitney U test. This study was performed independently at least three times, and one representative set is shown. BW body weight; N.D. not detected; ns, not significant; NT non-treated. Source data are provided as a Source Data file.