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Prevalence of AAV2.5 neutralizing antibodies in synovial fluid and serum of patients with osteoarthritis

Gene Therapy volume 30, pages 587–591 (2023)Cite this article

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Abstract

Osteoarthritis (OA) is a leading cause of disability with no cure and only supportive therapy. Adeno-associated virus (AAV) serotype 2.5 is being used in a Phase I clinical trial to deliver the interleukin-1 receptor antagonist into knee joints with OA. Neutralizing antibodies (Nab) directed against AAV2.5, if present, could inhibit gene transfer. Here, we report the prevalence of AAV2.5 Nab in the sera and synovial fluids of patients with OA. Nab titers were measured by their ability to inhibit in vitro transduction by AAV2.5 encoding GFP. Of 44 synovial fluids from patients with mid-stage and advanced OA, 43% had undetectable Nab; 25% had low titers (<1:100), 16% had medium titers (1:100–1:1000) and 16% had high titers (>1:1000) of Nab. Titers of AAV2.5 Nabs correlated with those of AAV2, but not with those of AAV5. Serum titers of AAV2.5 Nab correlated positively with titers in synovial fluid, and were never less than the matched synovial fluid titers. These findings suggest that high titers of Nab against AAV2.5 are uncommon in the synovial fluids of patients with OA, and individuals with high synovial fluid Nab titers can be identified by measuring titers in the serum.

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Fig. 1: Summary of methods used and salient results.

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Acknowledgements

This work was supported by award number W81XWH-16-1-0540 from the Department of Defense. Dr. Abdul was supported by NIH training grant number NIH-NICHD T32 - 5T32GM00868F20. Dr. Evans’s research is supported, in part, by the John and Posy Krehbiel Professorship in Orthopedics. Figure 1 was created with BioRender.com.

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Authors and Affiliations

  1. Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN, USA

    Temilola Y. Abdul, Gresin P. Hawse, Jay Smith, Jacob L. Sellon, Michael J. Coenen, Christopher H. Evans & Rodolfo E. De La Vega

  2. Mary Free Bed Rehabilitation Hospital, Grand Rapids, MI, USA

    Temilola Y. Abdul

  3. Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA

    Jacob L. Sellon, Matthew P. Abdel, Christopher H. Evans & Rodolfo E. De La Vega

  4. The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, Woolloongabba, Australia

    James W. Wells

  5. Department of Cellular Biology Inspired Tissue Engineering, MERLN Institute, Maastricht University, Maastricht, the Netherlands

    Rodolfo E. De La Vega

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  1. Temilola Y. Abdul
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  2. Gresin P. Hawse
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  7. Michael J. Coenen
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  8. Christopher H. Evans
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Contributions

JS, JLS, MPA: Sample acquisition. TYA, GPH, JWW, MJC, REDLV: Assay development and implementation. REDLV, TYA, CHE: Data analysis. CHE, REDLV: Manuscript preparation.

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Correspondence to Christopher H. Evans.

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Competing interests

CHE is a co-founder of Genascence Inc., which is running a Phase I clinical trial in this area (ClinicalTrials.gov Identifier: NCT02790723).

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Mayo Clinic Institutional Review Board approval (IRB# 16-009183).

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Abdul, T.Y., Hawse, G.P., Smith, J. et al. Prevalence of AAV2.5 neutralizing antibodies in synovial fluid and serum of patients with osteoarthritis. Gene Ther 30, 587–591 (2023). https://doi.org/10.1038/s41434-022-00326-5

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  • DOI: https://doi.org/10.1038/s41434-022-00326-5

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