# Prevalence of Anti-Adeno-Associated Virus Immune Responses in International Cohorts of Healthy Donors

Article · Kruzik A, Fetahagic D, Hartlieb B, Dorn S, Koppensteiner H, Horling FM, Scheiflinger F, Reipert BM, de la Rosa M

- Archive id: doi:10.1016/j.omtm.2019.05.014
- Published: 2019-06-07
- Venue: Molecular therapy. Methods & clinical development
- DOI: https://doi.org/10.1016/j.omtm.2019.05.014
- PMID: 31338384
- PMCID: PMC6629972
- Citations: 160
- Source URL: https://doi.org/10.1016/j.omtm.2019.05.014
- PDF: https://europepmc.org/articles/PMC6629972/pdf
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Gene & Cell Therapy](https://space-kitty.com/topics/gene-cell-therapy)

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