Clearance of hFVIII in the two vector groups immediately after the secondary FVIII immunization. At time zero, 1 μg of clinical grade hFVIII was injected i.v., and at the times indicated, plasma was collected and hFVIII was measured by ELISA as described in Materials and Methods. Data shown are average detectable plasma concentrations of hFVIII ± SD for the LNL6 control animals (A; n = 9), for the GCsamF8EN low titer anti-hFVIII antibody responders (B, filled symbols, n = 6), and the GCsamF8EN high titer responders (B, open symbols, n = 3). The broken lines represent hFVIII clearance in FVIII-naive, untreated exon 17 FVIII-deficient mice, determined in separate experiments.