Preexisting anti-adeno-associated virus neutralizing antibodies (Anti-AAV NAb)

Preexisting anti-adeno-associated virus (AAV) neutralizing antibodies (NAbs) are host immunoglobulins formed following natural exposure to wild-type AAV, which is prevalent in the human population. These antibodies represent a major hurdle in the field of gene therapy because they can bind to the AAV capsid of therapeutic vectors, preventing cellular entry and subsequent transgene expression. Even low titers of these antibodies can completely neutralize the efficacy of intravenously administered gene therapies, leading to the exclusion of a significant percentage of patients from clinical trials and approved treatments. To address this, researchers are developing strategies such as the use of IgG-cleaving enzymes like imlifidase to transiently clear antibodies, or utilizing plasmapheresis to physically remove them before vector administration. Additionally, engineering novel AAV capsids that 'escape' detection by these antibodies is a primary focus of next-generation gene therapy development.

Other names

Anti-AAV antibodiesAAV neutralizing antibodiesNeutralizing antibodies to AAV capsidsPreexisting AAV immunityAnti-capsid antibodies

Drugs targeting these antibodies typically function through proteolytic cleavage of IgG (e.g., imlifidase), depletion of B-cells or plasma cells to prevent production (e.g., rituximab, bortezomib), or physical removal from the blood via plasmapheresis.