Anti-adeno-associated virus 9 neutralizing antibody (Anti-AAV9 NAb)

Anti-adeno-associated virus 9 (AAV9) neutralizing antibodies are host-produced immunoglobulins that recognize and bind to the AAV9 capsid, preventing the viral vector from delivering its therapeutic genetic payload to target cells [1]. These antibodies often arise from natural exposure to wild-type AAV9 or from previous administrations of AAV-based gene therapies, with seroprevalence in the human population estimated between 30% and 50% [2]. In the context of gene therapy, particularly for treating Spinal Muscular Atrophy (SMA) with onasemnogene abeparvovec, the presence of high titers of these antibodies is a significant contraindication as they can completely abolish the efficacy of the treatment [3]. Therapeutic interventions to address this target include the use of IgG-degrading enzymes like imlifidase, plasmapheresis, or intensive immunosuppressive regimens to transiently lower antibody levels [4]. Managing anti-AAV9 antibodies is critical for expanding the eligible patient population for life-saving gene therapies and ensuring successful vector transduction [5]. Sources: [1] Naso et al., 2017, BioDrugs; [2] Boutin et al., 2010, Gene Therapy; [3] Mendell et al., 2017, NEJM; [4] Leborgne et al., 2020, Nature Medicine; [5] Mingozzi & High, 2013, Nature Reviews Genetics; [6] Jordan et al., 2020, Gene Therapy.

Other names

Anti-AAV9 antibodyAAV9 neutralizing antibodyAAV9 NAbAnti-AAV9 IgGPre-existing AAV9 antibodies

Therapeutic strategies targeting anti-AAV9 neutralizing antibodies involve the enzymatic cleavage of IgG molecules (e.g., imlifidase), physical removal from the blood via plasmapheresis, or the depletion of antibody-producing B-cells and plasma cells to create a transient window for successful viral vector transduction [4, 6].