Dose-dependent immunogenicity of wt fVIII, R372A/R1689A fVIII, and V634M fVIII in fVIII^−/− mice. Cohorts (n = 9-10) of fVIII^−/− were injected with 4 weekly doses of fVIII construct (0.5, 1.0, 1.5, or 2.0 μg) weekly, followed by a single boost dose at twice the weekly dose. One week after the last dose plasma was collected for both (A) anti-fVIII ELISA titers and (B) fVIII inhibitor titers. Graphs show medians and interquartile ranges.