Neutralizing antibodies against Adeno-associated virus serotype 9 capsid (AAV9 NAb)

Neutralizing antibodies against the Adeno-associated virus serotype 9 (AAV9) capsid are host-derived immunoglobulins, primarily of the IgG class, that recognize and bind to the AAV9 viral vector [1, 3]. These antibodies are prevalent in the human population due to natural exposure to wild-type AAV9 or can be induced by the administration of AAV9-based gene therapies, which currently limits treatment to a single dose [3, 4]. In clinical applications such as the treatment of Spinal Muscular Atrophy (SMA) with onasemnogene abeparvovec, the presence of these antibodies can neutralize the therapeutic vector before it reaches target cells, significantly reducing efficacy and potentially triggering inflammatory responses [2]. To overcome this barrier, researchers utilize IgG-cleaving enzymes like Imlifidase to transiently remove circulating antibodies or employ immunosuppressive regimens to prevent their formation [1, 4]. Monitoring NAb titers is a critical component of patient screening and stratification for systemic AAV9 gene delivery [2]. Citations: [1] Leborgne et al. (2020) Nature Medicine; [2] Zolgensma Prescribing Information (Novartis); [3] Boutin et al. (2010) Gene Therapy; [4] Mingozzi & High (2013) Blood.

Other names

Anti-AAV9 antibodiesAAV9 neutralizing antibodiesPre-existing anti-AAV9 immunityAAV9-specific immunoglobulinsAnti-AAV9 IgG

Therapeutic strategies involve the enzymatic cleavage of the IgG hinge region to abolish effector functions and neutralization capacity, or the depletion of B-cells and plasma cells to reduce antibody production, thereby allowing AAV9-based gene therapy vectors to reach target tissues [1, 4].