Anti-adeno-associated virus rhesus isolate 74 neutralizing antibody (Anti-AAVrh74 NAb)

Anti-adeno-associated virus rhesus isolate 74 (AAVrh74) neutralizing antibodies are host-produced immunoglobulins that recognize and bind to the AAVrh74 capsid, preventing the viral vector from delivering its genetic payload into target cells (PMID: 31600478). These antibodies can be pre-existing due to natural exposure to wild-type AAVs or can be induced following an initial dose of gene therapy, effectively precluding repeat administration (PMID: 32483358). In the clinical setting, particularly for treatments like delandistrogene moxeparvovec (Elevidys) for Duchenne muscular dystrophy, the presence of these antibodies is a primary exclusion criterion because even low titers can significantly diminish therapeutic efficacy (FDA, Elevidys Prescribing Information). To overcome this barrier, researchers are investigating the use of IgG-cleaving enzymes like imlifidase or plasmapheresis to transiently deplete these antibodies before vector administration (PMID: 32483358). Managing anti-AAVrh74 neutralizing antibodies is critical for expanding patient eligibility and ensuring the safety and success of AAV-based genetic medicines.

Other names

Anti-AAVrh74 neutralizing antibodiesAAVrh74 neutralizing antibodiesAnti-AAVrh74 NAbsAnti-AAVrh74 IgGPre-existing AAVrh74 antibodies

Enzymatic cleavage of the IgG hinge region by imlifidase to eliminate neutralizing activity (PMID: 32483358).