Efficacy and immunogenicity of the expression of FVIII variants in the HA mouse model. Transgenic HA mice tolerant to human FVIII-BDD due to platelet-restricted FVIII expression received AAV8 vector encoding for FVIII-RH (n = 10) or FVIII-BDD (n = 7). (A) Circulating antigen levels of FVIII at 8 weeks after vector injection are shown in the graph. (B) The graph shows inhibitory antibody detected by Bethesda assay. Positive controls included nontolerant HA mice (n = 6) with antibody to human FVIII following repeated injections with recombinant FVIII protein. (C) The graph shows mouse anti-human FVIII antibody detected by enzyme-linked immunosorbent assay. (D) The graph shows humoral responses to AAV serotype 8 capsid at baseline and at 6 weeks after AAV injection at doses of 8 × 1012 vg/kg of AAV-FVIII-RH (n = 10) or AAV-FVIII-BDD (n = 7). P value is indicated.
