Adeno-associated virus serotype 2 and 3 neutralizing antibodies (AAV2/3 NAbs)

Adeno-associated virus serotype 2 and 3 (AAV2/3) neutralizing antibodies are host-produced immunoglobulins, primarily of the IgG class, that bind to the viral capsid of AAV serotypes 2 and 3 (Mingozzi & High, 2013, Blood). These antibodies are common in humans due to natural exposure to wild-type AAV, with seroprevalence rates often exceeding 30-70% depending on the population and serotype (Boutin et al., 2010, Gene Therapy). In the context of gene therapy, these antibodies act as a significant barrier by binding to the therapeutic AAV vector in the bloodstream, preventing cell entry and subsequent transgene expression (Calcedo et al., 2009, Journal of Infectious Diseases). This neutralization can render a gene therapy completely ineffective even at low titers, posing a major challenge for systemic administration. To address this, therapeutic strategies such as the use of imlifidase, an IgG-cleaving enzyme, or plasmapheresis are employed to transiently deplete these antibodies prior to vector administration (Leborgne et al., 2020, Nature Medicine). Consequently, screening for AAV2/3 neutralizing antibodies is a critical step in patient selection and clinical trial design for AAV-based gene therapies (Wang et al., 2019, Nature Reviews Drug Discovery).

Other names

Anti-AAV2 antibodiesAnti-AAV3 antibodiesAAV2/3-specific neutralizing antibodiesPre-existing AAV immunityAnti-capsid antibodies

Proteolytic cleavage of the IgG heavy chain (e.g., by imlifidase), physical removal from circulation via plasmapheresis, or suppression of antibody-producing B-cells to prevent the neutralization of viral gene therapy vectors.