Efficient removal of antibodies to adeno-associated viruses by immunoadsorption

Gene therapies based on adeno-associated viruses (AAV) are a therapeutic option to successfully treat monogenetic diseases. However, the influence of pre-existing immunity to AAV can compromise the application of AAV gene therapy, most notably by the presence of neutralizing antibodies to AAV. In the following study we investigated to what extent the treatment by immunoadsorption (IA) would reduce the levels of human anti-AAV antibodies to AAV2 and AAV5. To that end, we analyzed blood sera from patients receiving IA treatment because of underlying autoimmune disease or transplant rejection. Our results show that IA efficiently reduces pre-existing anti-AAV antibodies with continuous lowering of neutralizing antibodies to below the threshold titer of 1:5 in 45% (anti-AAV2) and 80% (anti-AAV5) of the patients, respectively, after three to five single IA treatments. In summary, IA may represent a safe strategy to precondition patients with pre-existing AAV antibodies to make this population eligible for an effective AAV-based gene therapy.