{"id":"doi:10.1016/j.omtm.2019.05.014","kind":"article","title":"Prevalence of Anti-Adeno-Associated Virus Immune Responses in International Cohorts of Healthy Donors","authors":["Kruzik A","Fetahagic D","Hartlieb B","Dorn S","Koppensteiner H","Horling FM","Scheiflinger F","Reipert BM","de la Rosa M"],"author_count":9,"year":2019,"published":"2019-06-07","venue":"Molecular therapy. Methods & clinical development","cited_by":160,"doi":"10.1016/j.omtm.2019.05.014","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.omtm.2019.05.014","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.omtm.2019.05.014","updated":null,"pmid":"31338384","pmcid":"PMC6629972","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC6629972/pdf","abstract":"Preexisting immunity against adeno-associated virus (AAV) is a major challenge facing AAV gene therapy, resulting in the exclusion of patients from clinical trials. Accordingly, proper assessment of anti-AAV immunity is necessary for understanding clinical data and for product development. Previous studies on anti-AAV prevalence lack method standardization, rendering the assessment of prevalence difficult. Addressing this need, we used clinical assays that were validated according to guidelines for a comprehensive characterization of anti-AAV1, -AAV2, -AAV5, and -AAV8 immunity in large international cohorts of healthy donors and patients with hemophilia B. Here, we report a higher than expected average prevalence for anti-AAV8 (∼40%) and anti-AAV5 (∼30%) neutralizing antibodies (NAbs), which is supported by strongly correlating anti-AAV IgG antibody titers. A similar anti-AAV8 NAb prevalence was observed in hemophilia B patients. In addition, a high co-prevalence of NAbs against other serotypes makes switching to gene therapy using another serotype difficult. As anti-AAV T cell responses are believed to influence transduction, we characterized anti-AAV T cell responses using interleukin-2 (IL-2) and interferon-γ (IFN-γ) ELISpot assays, revealing a similar prevalence of IFN-γ responses (∼20%) against different serotypes that did not correlate with NAbs. These data, along with the long-term stability of NAbs, emphasize the need to develop strategies to circumvent anti-AAV immunity.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Prevalence of Anti-Adeno-Associated Virus Immune Responses in International Cohorts of Healthy Donors\" by Kruzik A, Fetahagic D, Hartlieb B et al., https://doi.org/10.1016/j.omtm.2019.05.014, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"gene-cell-therapy","name":"Gene & Cell Therapy","domain_slug":"medicine"}],"cited_in_dossiers":[]}