Figure 1.

Initiation and reactivation of adaptive immune responses to adeno-associated virus (AAV). During natural infection with wild-type (WT) AAV, capsid-specific adaptive immune responses can be triggered, with the development of anti-AAV antibodies and the establishment of a pool of long-lasting capsid-reactive memory B and T lymphocytes. Upon in vivo administration of recombinant AAV (rAAV) vectors, pre-existing anti-AAV antibodies can neutralize vector particles, while memory lymphocytes can be reactivated and expanded, leading to the de novo production of anti-AAV antibodies or, potentially, to the destruction of transduced cells presenting capsid-derived antigens.