Fig. 7
Anti-AAV2/8 passive immunisation diminishes the AAV2/8-insulin-mediated therapeutic effect in diabetic NODscid mice. a NODscid male mice rendered diabetic with streptozotocin (40 mg/kg i.p. for 5 days) were treated with 5 × 109 vg AAV2/8-HLP-hINSco (indicated as AAV2/8) (day 0). The serum of immunocompetent NOD mice either injected with 5 × 109 vg or vehicle only was injected i.p. into the NODscid mice 4 days after the beginning of the therapy and for the following 7 days. The start date of passive immunisation was temporally determined by the appearance of anti-AAV8 antibody response in the immunocompetent NOD mice via ELISA. Blood glucose levels of treated animals monitored over time represented both as average measurements ± SE (b, left) and as a resulting percentage of diabetic mice (b, right). Statistical difference measured against diabetic control. Ns = non significant, *(p ≤ 0.05), log rank survival test. c NOD serum used to passively immunise AAV2/8-insulin-treated NODscid has AAV2/8 blocking capabilities conferred by anti-AAV2/8-neutralising antibodies. Percentage of cell transduction in an in vitro viral neutralising assay. Number of transduced cells was normalised to positive control. AAV2/8 haemophilic represents a serum sample coming from an AAV2/8-treated dog known to have developed immunity against the vector. Statistical difference compared to positive control, *(p ≤ 0.05), **(p ≤ 0.01), two-way Anova
