Authors:	Boedecker-Lips, Simone Judel, Andreas Holtz, Stefan Mayer, Magnus Klimpke, Pascal Kraus, Daniel Schreiner, Thomas Gerstmayer, Bernhard Eulitz, Klaus Mayer, Magnus Christopher Weinmann-Menke, Julia
Title:	Efficient removal of antibodies to adeno-associated viruses by immunoadsorption
Online publication date:	29-Sep-2023
Year of first publication:	2023
Language:	english
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.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-9513
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Journal of clinical apheresis Version of Record (VoR)
Publisher:	Wiley Interscience
Publisher place:	New York, NY
Issue date:	2023
ISSN:	1098-1101
Publisher DOI:	10.1002/jca.22069
Appears in collections:	DFG-491381577-H