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

T.Y. Abdul, G.P. Hawse, J. Smith, J.L. Sellon, M.P. Abdel, J.W. Wells, M.J. Coenen, C.H. Evans*, R.E. De La Vega

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Number of pages5
JournalGene Therapy
Publication statusE-pub ahead of print - 9 Mar 2022



Cite this