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. 2023 Oct;38(5):590-601.
doi: 10.1002/jca.22069. Epub 2023 Jul 7.

Efficient removal of antibodies to adeno-associated viruses by immunoadsorption

Simone Boedecker-Lips  1 , Andreas Judel  2 , Stefan Holtz  1 , Magnus Mayer  1 , Pascal Klimpke  1 , Daniel Kraus  1 , Thomas Schreiner  3 , Bernhard Gerstmayer  3 , Klaus Eulitz  2 , Magnus Christopher Mayer  2 , Julia Weinmann-Menke  1   4
Affiliations

Efficient removal of antibodies to adeno-associated viruses by immunoadsorption

Simone Boedecker-Lips et al. J Clin Apher. 2023 Oct.

Abstract

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.

Keywords: adeno-associated viral vector-based gene therapies; adeno-associated virus; antibody; immunoadsorption; immunoglobulin; monogenetic diseases; plasmapheresis.

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References

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