Anti-AAV8 NAb responses in mice treated with BAX 335 vs CpG-depleted vector constructs. Anti-AAV8 NAb responses, as a surrogate marker for immune activation via TLR9, indicate lower immunogenicity for CpG-depleted vectors. C57BL/6J mice (8-10 weeks old, n = 6-8 per group) were treated IV with identical doses (4 × 10¹² vg/kg) of either one of two AAV8 vectors carrying an FIX Padua coding sequence with different numbers of CpG oligodeoxynucleotides (ODNs): BAX 335 (99 CpG ODNs); CpG-depleted candidate (0 CpG ODNs). Blood was collected 4 weeks later, and the magnitude of the resulting titer of anti-AAV8 NAbs was assayed as a marker of adaptive immune responses to CpG ODNs.