Induction of immune tolerance to coagulation factor IX antigen by in vivo hepatic gene transfer
J. Clin. Invest. Federico Mingozzi, et al. 111:1347 doi:10.1172/JCI16887 [
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Figure 1Plasma levels of hF.IX and anti-hF.IX (measured by ELISA or immuno-capture assay) in immune-competent mice as a function of time after liver-directed vector administration (AAV-EF1α-hF.IX vector). (
a–
d) hF.IX in ng/ml. (
e–
h) IgG anti-hF.IX in ng/ml. Red lines: IgG-1; blue lines IgG-2a; green lines: IgG-2b. (
a and
e) C57BL/6 mice (
n = 4, 1 × 1011 vg/animal). (
b and
f) BALB/c mice (
n = 4, 1 × 1011 vg/animal). (
c and
g) C3H mice (
n = 4, 1 × 1011 vg/animal). (
d and
h) C3H mice (
n = 5, 5 × 1011 vg/animal). Each line represents an individual animal. Symbols are identical for hF.IX and anti-hF.IX levels of the same animal (note that only one animal in
f had an anti-hF.IX response). Vertical arrows indicate challenge by subcutaneous administration of 2 μg hF.IX formulated in CFA.
