Neutralizing anti-adeno-associated virus antibodies (Anti-AAV NAb)

Neutralizing anti-adeno-associated virus (AAV) antibodies are host-produced immunoglobulins that recognize and bind to the capsid proteins of AAV vectors used in gene therapy. These antibodies are often pre-existing in the human population due to natural exposure to wild-type AAV or can be induced following the first administration of a gene therapy product (Boutin et al., 2010, Gene Therapy). When present, they bind to the viral vector and prevent it from transducing target cells, thereby significantly reducing or completely neutralizing the therapeutic efficacy of the treatment (Mingozzi & High, 2013, Blood). In clinical practice, high titers of these antibodies often serve as an exclusion criterion for patients seeking gene therapy. Current pharmacological strategies to address this challenge include the use of IgG-cleaving enzymes like imlifidase, which transiently depletes the antibodies to create a window for vector administration, or the use of immunosuppressive regimens to prevent their formation (Leborgne et al., 2020, Nature Medicine). Managing these antibodies is critical for the success of systemic gene delivery and for the possibility of repeat dosing in patients.

Other names

Anti-AAV neutralizing antibodiesAAV-specific neutralizing antibodiesPre-existing AAV antibodiesNeutralizing antibodies to AAV capsidsNAbs

Enzymatic cleavage of IgG to deplete neutralizing antibodies, depletion of B cells to prevent antibody production, or physical removal via plasmapheresis to enable viral vector transduction.