Infrequent ADA responses accompany loss of serum transgene mAb.

(A) Serum mAb measurements in injected animals that did (+) or did not (-) develop anti-ITS01 (left) and/or anti-ITS06.02 (right). Hashed lines denote the limit of ITS01 or ITS06.02 positivity (2 SD above mean of negative control serum) at 1.3 μg/ml, blue and 0.8 μg/ml, red, respectively). Asterisks indicate statistical significance (p ≤ 0.05). (B) Polyclonal serum ADA responses were quantified in relative μg/ml equivalents to monoclonal control anti-idiotype antibodies. Hashed lines denote anti-ITS01 or anti-ITS06.02 threshold of positivity set at 1 RU. Dose and AAV treatments are coded by color (Control, low (2 x 10¹¹ gc/animal; blue), medium (2 x 10¹² gc/animal; red), intermediate (5 x 10¹² gc/animal; green), and high (2 x 10¹³ gc/animal; purple)) and shape denotes antibody delivered: control (diamonds), ITS01 (squares), ITS06.02 (circles), ITS01 + ITS06.02 (upward triangles), ITS01 + ITS06.02 + ITS52 (downward triangles). (C) Serum ADA response estimates (hashed lines) and AAV mAb estimates (solid lines) are shown for ITS01 (blue) and ITS06.02 (red) for 3 representative examples of animals that developed no ADA (top panel), ADA against both mAbs (middle panel), or ADA against only one mAb (bottom panel).