(A and B) AAV2H22 or AAV2 virions were allowed to bind the apical surfaces of pig airway (A) or alveolar (B) epithelia at the indicated doses for 1 hour at 4°C. In airway epithelia, AAV2H22 (blue) plateaued at 6 × 1010 VG, whereas AAV2 (green) did not reach saturation. In alveolar epithelia, both AAV2 and AAV2H22 saturated, but AAV2 had more apparent binding sites. n = 6–12. (C) Consistent with B, AAV2-GFP transduced pig alveolar epithelia more efficiently than AAV2H22-GFP. n = 6; *P < 0.01, Mann-Whitney nonparametric t test. (D) In contrast to pig, AAV2H22-GFP did not infect human airway epithelia. n = 3 from different donors in 4 different experiments; *P < 0.01, Mann-Whitney nonparametric t test.