Adaptive immune receptors recognizing Adeno-associated virus serotype 9 (AAV9) capsid epitopes (Anti-AAV9 receptors)

Adaptive immune receptors recognizing Adeno-associated virus serotype 9 (AAV9) capsid epitopes include B-cell receptors (BCRs), secreted antibodies, and T-cell receptors (TCRs) that specifically target the viral protein shell of the AAV9 vector (Mingozzi & High, 2013, Nature Reviews Genetics). These receptors are critical components of the host immune system that identify AAV9 as a foreign pathogen, potentially leading to the failure of gene therapy treatments (Ertl, 2021, Frontiers in Immunology). Pre-existing neutralizing antibodies (NAbs) can bind to the AAV9 capsid in the systemic circulation, preventing the vector from reaching and entering target cells (Leborgne et al., 2020, Nature Medicine). Furthermore, AAV9-specific T-cell receptors recognize capsid-derived peptides presented on the surface of transduced cells, triggering a cytotoxic response that eliminates the cells and the therapeutic transgene (Schanz et al., 2021, Molecular Therapy). This immune recognition is a major safety concern, as it can cause severe inflammation and tissue damage, such as hepatotoxicity, in patients receiving high doses of AAV9-based therapies like onasemnogene abeparvovec (Zolgensma Prescribing Information). To mitigate these effects, clinicians use drugs like Imlifidase to degrade existing antibodies or corticosteroids to suppress T-cell activity. Research into these receptors also informs the design of next-generation AAV capsids that can evade detection by the adaptive immune system (Tse et al., 2017, Emerging Microbes & Infections).

Other names

Anti-AAV9 antibodiesAAV9-specific T-cell receptorsAnti-AAV9 neutralizing antibodiesAAV9-specific BCRsAnti-AAV9 NAbs

Enzymatic cleavage of IgG antibodies, depletion of B-cells and plasma cells, and systemic suppression of T-cell activation to prevent vector neutralization and cellular rejection.