Anti-adeno-associated virus 8 antibodies (Anti-AAV8 antibodies)

Anti-adeno-associated virus 8 (AAV8) antibodies are immunoglobulins, primarily of the IgG subclass, that specifically recognize and bind to the capsid proteins of the AAV8 viral vector. These antibodies are prevalent in a significant portion of the human population due to natural exposure to wild-type AAV8 or can be induced following an initial administration of AAV8-based gene therapy. In the context of clinical gene therapy, these antibodies serve as a critical therapeutic target for removal or neutralization because they bind to and neutralize the AAV8 vector, preventing it from reaching and transducing target cells, such as hepatocytes. This neutralization significantly impairs the efficacy of gene-based medicines for conditions like hemophilia and Crigler-Najjar syndrome. Therapeutic strategies targeting these antibodies include the use of IgG-cleaving enzymes like imlifidase, which proteolytically degrades the antibodies to create a transient window for vector administration. Other approaches involve plasmapheresis, immune adsorption, or B-cell depletion therapies to lower antibody titers. Monitoring the levels of these antibodies through neutralizing antibody (NAb) or total binding antibody (TAb) assays is a standard practice for patient stratification and determining treatment eligibility in AAV8-mediated gene therapy trials.

Other names

Anti-AAV8 monoclonal antibodiesAnti-AAV8 neutralizing antibodiesAnti-AAV8 IgGAAV8-specific antibodiesAnti-AAV8 NAbsAnti-AAV8 total binding antibodies

Proteolytic cleavage of IgG, B-cell depletion, and inhibition of antibody-secreting plasma cells to reduce neutralizing antibody titers.