Figure 4. In Silico modeling predicts increased intact antigen accumulation on FDCs for extended dosing compared to bolus immunization.

(A) Schematic showing antigen fates considered in the computational model. (B) In silico prediction of the amount of free antigen in lymph nodes over time in an intact (“soluble native”) or degraded (“soluble non-native”) state, and amounts of native and non-native antigen captured on FDCs in the form of immune complexes (“IC”) over time. The antigen amounts are normalized to the total antigen dose in immunization. (C) Antibody titers predicted by the in silico model for bolus, 2-ED, and 7-ED immunization regimens. In the simulation, antibody titers are defined as the concentration of antibodies weighted by their affinities, reflecting their capabilities to bind to the antigen. (D) Comparison of predicted antigen amounts accumulated on FDCs after the final shot from each dosing scheme, normalized to the total antigen dose in immunization. (E) Model prediction for the number of GC B cells over time. (F, G) Model prediction for the number of native antigen-binding (i.e. trimer⁺) GC B cells over time (F) and frequency of trimer⁺ GC B cells at day 21 (G) from bolus, 2-ED, and 7-ED immunization schemes. The results reported are mean values from 10 independent stochastic simulations of the lymph node. ****, p < 0.0001; by one-way ANOVA with Tukey’s multiple comparison post test.