antiAAV9

antiAAV9 refers to antibodies directed against the adeno-associated virus serotype 9 (AAV9) capsid. These antibodies can be present in individuals due to natural exposure to AAV9 or generated after administration of AAV9-based gene therapy vectors. antiAAV9 can comprise binding antibodies and neutralizing antibodies, with the latter capable of blocking vector binding and entry into target cells.

In gene therapy, antiAAV9 poses a critical challenge because it can reduce transduction efficiency, cause variability in therapeutic effect, and complicate or preclude repeat dosing. Seroprevalence of antiAAV9 varies by population, age, and geographic region, and neutralizing antibodies are typically most relevant for limiting systemic delivery of AAV9 vectors. The presence and level of antiAAV9 are often used to assess eligibility for clinical intervention and to predict potential outcomes.

Detection and assessment of antiAAV9 commonly involve neutralizing antibody (NAb) assays and binding antibody assays. These tests guide patient selection and dosing strategies, as assay differences can influence the interpretation of antibody thresholds. Thresholds for successful treatment are not universally standardized and depend on the specific vector, dose, and assay used.

Mitigation strategies under investigation include using alternative AAV serotypes or engineered capsids with reduced antibody binding, transient immunosuppression, plasmapheresis to reduce circulating antibodies, or dosing strategies that saturate antibodies with decoy capsids. Researchers continue to study cross-reactivity between AAV serotypes and the implications for re-dosing and long-term efficacy.

See also: AAV9, adeno-associated virus, neutralizing antibodies, gene therapy.