Fig. 7. Zabadinostat augments the level of GC B cells through modulating the activity of Tfh cells.

a Schematic representation of the immunogenicity experiment with zabadinostat and spike S1 protein. Balb/c mice were treated with orally administrated zabadinostat at 25 mg/kg (days 1–3) or 12.5 mg/kg (days 8–11), and intravenous spike S1 protein (10 µg) (days 0 and 7) with respect to vehicle-only control; splenocytes were collected at day 14; b relative body weight representation of treated and non-treated mice; n = 4; results presented as mean values +/−SD; c follicular T-cell level (CD4 + PD-1 + CXCR5 + positive T cells), germinal centre B cells (Fas+ PNA+ positive B cells) and intracellular cytokine IL-21 (in CD4-positive T cells), IFNy (in CD4 and CD8-positive T cells) secretion measurements by flow cytometry; n = 4; results presented as mean values +/−SD; one-way ANOVA. d Model describing the effect of zabadinostat in regulating the adaptive immune response. It is proposed that inhibition of histone deacetylase induces both cellular and humoral immune responses by increasing antigen presentation (e.g., by dendritic cells), activating T and B cells and increasing germinal centre B cells (stimulated by follicular T cells), which coincides with elevated the MHC class I and II proteins.