%0 Figure %A Welles, Hugh C. %A F. Jennewein, Madeleine %A D. Mason, Rosemarie %A Narpala, Sandeep %A Wang, Lingshu %A Cheng, Cheng %A Zhang, Yi %A Todd, John-Paul %A D. Lifson, Jeffrey %A B. Balazs, Alejandro %A Alter, Galit %A B. McDermott, Adrian %A Mascola, John R. %A Roederer, Mario %D 2018 %T Infrequent ADA responses accompany loss of serum transgene mAb. %U https://plos.figshare.com/articles/figure/Infrequent_ADA_responses_accompany_loss_of_serum_transgene_mAb_/7427291 %R 10.1371/journal.ppat.1007395.g004 %2 https://ndownloader.figshare.com/files/13847615 %K AAV-directed muscle cell expression %K anti-transgene antibody response %K target antibody abundance %K AAV-based approaches %K Vectored delivery %K autologous anti-SIV neutralizing antibodies %K immunization strategy %K animal model %K Vectored transgene expression %K plasma expression %K mucosal accumulation %K transgene mAb %K dose SIVsmE 660 swarm challenge %K dose intrarectal swarm SIVsmE 660 challenge Gene %K injection %K glycosylation profiles %K anti-SIV envelope %K anti-vector antibody responses %K AAV 8 %K nonhuman primate model %K Adeno-Associated Virus 8 %K HIV %K gene therapy-based %K immunity %K 2 x 10 12 AAV 8 genome copies %K mucosal surfaces %K rhesus macaques %X

(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).

%I PLOS Pathogens