March 23rd, 2018 - Mingozzi et al. 2015, Adeno-associated viral vectors at the frontier between tolerance and immunity, Frontiers in Immunology, Vol. (6); Article 120.


“Although both PRRs are part of the same family, recognition of the viral capsid caused induction of a Nuclear Factor kB-dependent inflammatory response (14), while activation of TLR-9 induced secretion of type I interferon (IFN) that was found to be enhanced if vectors with self-complementary (sc) AAV vector genomes were used (15, 16). The nature of this enhanced immunogenicity remains to be clarified, but is maybe related to a negative impact of sc vector genomes on capsid stability (16) or to the additional inverted terminal repeat (ITR) sequence present in sc vector genomes (8). The later hypothesis would be in line with a recent study reporting significantly reduced adaptive immune responses toward the capsid and transgene product when using AAV vectors with a reduced number of CpG motifs, which are known TLR9 PAMP [Faust et al.].”
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