Understanding Immunogenicity In AAV Gene Therapy

As adeno-associated virus (AAV)-based gene therapies progress toward clinical use, effectively managing immunogenicity risk is critical to patient selection, therapeutic durability, and regulatory success. This expert-authored white paper offers a comprehensive, science-driven roadmap for designing and validating immunogenicity assays that are both analytically robust and globally compliant. It delivers practical strategies for every development stage — from preclinical studies to global regulatory submissions — with detailed comparisons of total antibody (TAb) and neutralizing antibody (NAb) assays, highlighting differences in format, throughput, sensitivity, and translational relevance.

The guide outlines best practices for assay selection, validation, and deployment, including cutoff determination, reagent qualification, and alignment with evolving US (IDE, SRD, Q-submissions) and EU (IVDR) requirements. It also addresses the integration of immune response data with clinical endpoints to refine patient stratification and optimize study design. Whether supporting early-phase protocols, preparing companion diagnostics, or meeting diverse regulatory expectations, this resource equips developers with the technical insights and regulatory awareness needed to strengthen assay strategy and advance gene therapy programs with greater confidence and efficiency.