Modulation of anti-FVIII immune response by CpG-ODN in vivo. Hemophilic mice were treated intravenously with 1 dose of 200 ng of FVIII on day 1 to prime the immune system for further exposure to FVIII. On day 8, mice received either buffer or CpG-ODN to stimulate the innate immune system. On day 9, mice received either PBS buffer, FVIII, or FVIII together with different doses of CpG-ODN. On day 16, blood samples were taken for the analysis of circulating anti-FVIII antibodies. (A) Treatment schedule. (B) Titers of anti-FVIII antibodies together with medians for each group. Each point represents the results of an individual mouse. Results presented were confirmed in 2 independent experiments.