Fig. 6: Heterologous AdC68-HATRBD booster reinforces and broadens the humoral immunity of licensed SARS-COV-2 vaccine.

a Scheme of experiments. Mice were administrated three doses of 5 μg ZF2001 by i.m. route. After 4 weeks post-last vaccination, half of mice (n = 10 per group) received a homologous booster with 5 μg of ZF2001, the other half received a heterogenous i.n. booster with 5 × 107 IFU of AdC68-HATRBD. Serum and BALF were harvested at 12 weeks post-vaccination. b Serum RBD-specific lgG antibody responses to wild-type SARS-CoV-2 (WT) and BA.5. c, d BALF RBD-specific lgG (c) and lgA (d) antibody responses to WT and BA.5. e Serum pseudovirus neutralizing antibody responses against WT and Omicron variants. f Serum live virus neutralizing antibody responses. Each dot represents data from two mice. In (e) and (f), values of geometric mean titer (GMT) are displayed, the red dashed line represents the lower limit of detection, and the numbers after the up arrow indicate the median fold increase in antibody titer induced by heterogenous vaccination compared with homologous vaccination. Data are presented as mean ± SEM (b–d) or GMT ± SD (e, f). Significance was assessed by one-way ANOVA with Tukey correction. **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001.