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Updated: Jul 24, 2025
Author Spotlight: Improved Method for Production and Purification of Adeno-Associated Viral Vectors
Published on: April 5, 2024
Efficient removal of antibodies to adeno-associated viruses by immunoadsorption
Simone Boedecker-Lips1, Andreas Judel2, Stefan Holtz1
1Division of Nephrology, I. Department of Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Background:
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 (NAb) to AAV.
Methods:
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 screened blood sera from 40 patients receiving IA treatment because of underlying autoimmune disease or transplant rejection, with detectable AAV-antibodies in 23 patients (22 by NAb detection, and 1 additionally by anti-AAV5 ELISA analysis).
Results:
Our results show that IA efficiently depleted anti-AAV2 NAb with a mean reduction of 3.92 ± 1.09 log2 titer steps (93.4%) after three to five single IA treatments, 45% of seropositive subjects had an anti-AAV2 titer below the threshold titer of 1:5 after the IA treatment series. Anti-AAV5 NAb were reduced to below the threshold titer of 1:5 in all but one of five seropositive subjects. Analysis of total anti-AAV5 antibodies by ELISA demonstrated an anti-AAV5 antibody reduction over the IA treatment series of 2.67 ± 1.16 log2 titer steps (84.3%).
Conclusion:
In summary, IA may represent a safe strategy to precondition patients with pre-existing anti-AAV antibodies to make this population eligible for an effective AAV-based gene therapy.
