Time course of AAV-NAB response in hemophilia B dogs following vector administration. The limit of detection of AAV-NAB in these assays was 1:20. (A) AAV8-NAB response in 2 naive hemophilia B dogs (G43, ▪; H12, ○) following a single intraportal infusion of 5.25 × 10¹² GC/kg of AAV2/8 LSP-cFIX-W vector. (B) AAV2-and AAV8-NAB response in dog D39. D39 was first injected intraportally with AAV2 LSP-cFIX-W at a dose of 2.8 × 10¹² GC/kg, and 995 days after the first injection, the dog received a second intraportal injection with AAV2/8 LSP-cFIX-W vector at a dose of 5 × 10¹² GC/kg. ○ represents AAV2-NAB, and • represents AAV8-NAB. No pre-existing AAV-NAB was detected before the injections. (C) AAV2- and AAV5-NAB response in dog C52. C52 received a first intraportal injection of AAV2 LSP-cFIX at a dose of 2.8 × 10¹¹ GC/kg; 1180 days after the first injection, the dog received a second intraportal injection with AAV2/5 LSP-cFIX-W vector at a dose of 2.3 × 10¹³ GC/kg. ▵ represents AAV2-NAB, and ▴ represents AAV5-NAB.