Fig. 5
Intranasal RBDXBB.1.5-HR vaccine as a heterologous booster shot elicits superior mucosal and systemic immune responses. a, b NIH mice were immunized three doses of full-length BA.5 spike mRNA vaccine, followed by one dose of homologous injection of mRNA vaccine (4×mRNA), or one heterologous intranasal delivery of RBDXBB.1.5-HR vaccine (3×mRNA+1×IN). Mice in another group were received two injections of mRNA vaccine and subsequent two doses of intranasal RBDXBB.1.5-HR vaccine (2×mRNA+2×IN) (n = 6 mice per group). Endpoint titers of RBD-specific IgG in sera (c), and IgA and IgG in BALF samples (d). The neutralization against XBB-lineage and JN.1 pseudoviruses in sera (e) and BALF samples (f). The frequencies of (g) GC B, antigen-specific B cells, and (h) Tfh cells in mediastinal lymph nodes (n = 6 mice each group). i The absolute number of CD8+ and CD4+ TRM cells in BALF samples (n = 5 mice each group). j The percentages of antigen specific IFN-γ or TNF-α-producing memory CD4+ T cells in lung tissue (n = 6 mice each group). Data are presented as geometric mean values ± SD in c–f. The middle line indicates the median and the box shows the data range in g–j. P values were conducted by One-way ANOVA analysis followed by Tukey’s multiple comparison post hoc test in c, d and g–i. ****P < 0.0001; ***P < 0.001; **P < 0.01; *P < 0.05; ns not significant
