Anti-adeno-associated virus neutralizing antibody (Anti-AAV NAb)

Anti-adeno-associated virus (AAV) neutralizing antibodies (NAbs) are host-produced immunoglobulins that recognize and bind to the protein capsids of AAV vectors used in gene therapy (Mingozzi & High, 2013, Blood). These antibodies are prevalent in 30% to 70% of the human population due to natural exposure to wild-type AAV serotypes throughout life (Boutin et al., 2010, Gene Therapy). In the context of therapeutic delivery, NAbs pose a significant barrier by binding to the viral vector in the bloodstream, preventing the vector from reaching and transducing target tissues. This neutralization can lead to a complete loss of therapeutic efficacy, even at low antibody titers, which often results in the exclusion of seropositive patients from clinical trials (Leborgne et al., 2020, Nature Medicine). Therapeutic strategies to address this target include the use of IgG-cleaving enzymes like Imlifidase, which proteolytically degrades the antibodies to create a window for vector administration (Hansa Biopharma, 2023). Other approaches involve plasmapheresis to physically remove the antibodies or the use of immunosuppressive regimens to reduce antibody production. Managing these antibodies is critical for the success of systemic gene therapies for conditions such as Hemophilia and Spinal Muscular Atrophy.

Other names

AAV neutralizing antibodiesAnti-AAV antibodiesPre-existing AAV immunityNAbs

Proteolytic cleavage of IgG heavy chains by cysteine proteases (e.g., Imlifidase) to disable neutralization; depletion of antibody-producing B-cells or plasma cells to reduce titer levels.