Anti-adeno-associated virus capsid antibodies (Anti-AAV Abs)

Anti-adeno-associated virus (AAV) capsid antibodies are host immunoglobulins that recognize the protein shell of AAV vectors used in gene therapy. These antibodies can be pre-existing due to natural exposure to wild-type AAV, with prevalence rates often exceeding 50% in the general population, or induced following the administration of an AAV-based therapeutic (Boutin et al., 2010, Gene Therapy). They represent a primary obstacle in genomic medicine because they can bind to and neutralize the vector, preventing it from reaching target tissues and delivering its genetic payload (Mingozzi & High, 2013, Blood). High titers of neutralizing antibodies (NAbs) typically lead to patient exclusion from clinical treatments for conditions such as hemophilia or muscular dystrophy. To overcome this, researchers are utilizing IgG-cleaving enzymes like imlifidase to temporarily deplete these antibodies, thereby creating a window for successful vector administration (Leborgne et al., 2020, Nature Medicine). Additionally, FcRn inhibitors like nipocalimab are being explored to accelerate the clearance of these antibodies. Managing the immune response to the AAV capsid is critical for ensuring the safety and efficacy of systemic gene delivery and for enabling the possibility of re-dosing patients.

Other names

Neutralizing antibodies (NAbs)Anti-AAV antibodiesPre-existing AAV immunityAnti-capsid antibodiesAAV-specific immunoglobulins

Enzymatic cleavage of IgG by endopeptidases, physical removal through plasmapheresis, or inhibition of the neonatal Fc receptor (FcRn) to accelerate antibody clearance.