Dose and injection site number titration of AAV administration.

(A) Absolute (upper panels) or fractional (lower panels) serum antibody levels of ITS01, ITS06.02 or both are shown as a smoothed fit with 95% confidence interval shading for varying doses (left panels) or shots (right panels). At the lowest dose, data for a single animal is shown (the other one animal showed no expression of transgene). Animals received 2 injections into the quadriceps with AAV8-ITS01 and/or AAV8-ITS06.02 at low, medium, high doses (2 x 1011 (n = 1; green), 2 x 1012 (n = 24; cyan), 2 x 1013 (n = 6; violet) gc/animal, respectively). Controls received no injections (n = 16; gray). For varying shots, animals received 2 x 1012 gc/animal spread across 1, 2, 4, 8 injection sites (1: R quadriceps (n = 2; orange), 2: both quadriceps (n = 24; cyan), 4: both quadriceps and gastrocnemii (n = 2; magenta), 8: both quadriceps, gastrocnemii, deltoids and biceps (n = 2; blue), respectively). (B) Fractional mucosal transgene IgG is shown for individual macaques in mucosal compartments (n = 28). A scale adjustment is an x-axis break to emphasize early mucosal accumulation denoted by diagonal hashes between 4 and 5 weeks post AAV. (C) The correlation between serum versus rectal transgene mAb is shown for weeks 2, 4, and 5–24 post AAV. Points are colored by number of shots and point shapes denote dose, low, medium or high as noted in the legend.