Neutralizing antibodies against Adeno-associated virus 8 and Adeno-associated virus rh.10 (Anti-AAV8/AAVrh.10 NAbs)

Neutralizing antibodies (NAbs) against Adeno-associated virus 8 (AAV8) and AAVrh.10 are pre-existing immunoglobulins, primarily of the IgG class, that develop in humans following natural exposure to wild-type AAVs (Boutin et al., 2010; NIH, 1.1.2). These antibodies recognize and bind to specific epitopes on the viral capsid, such as the ADK8 epitope on AAV8, effectively blocking the vector's ability to bind to cell surface receptors or undergo endocytosis (Gurda et al., 2012; Harvard, 1.1.1). In the context of gene therapy, these NAbs represent a significant barrier, as even low titers can completely abrogate the efficacy of systemic treatments for diseases such as hemophilia B or spinal muscular atrophy (Frontiers, 1.2.5). To overcome this, researchers are developing desensitization protocols using drugs like imlifidase (an IgG-degrading enzyme) to transiently deplete these antibodies, or engineering stealth capsids that lack the recognized epitopes (Leborgne et al., 2020; NIH, 1.3.1). Monitoring NAb titers is a standard part of patient screening and clinical trial design for AAV-based therapies to ensure successful transduction and patient safety (NIH, 1.1.3).

Other names

Anti-AAV8 antibodiesAnti-AAVrh.10 antibodiesPre-existing AAV immunityAAV8/AAVrh.10 neutralizing antibodiesAnti-capsid antibodiesAAV neutralizing antibodies

Enzymatic cleavage of IgG antibodies to reduce neutralizing titers and facilitate viral vector transduction.