Pre-existing anti-adeno-associated virus 8 neutralizing antibodies (Anti-AAV8 NAb)

Pre-existing anti-adeno-associated virus 8 (AAV8) neutralizing antibodies are host-derived immunoglobulins, primarily of the IgG class, that develop following natural exposure to wild-type AAV8 [NIH, Frontiers in Immunology]. In the field of gene therapy, these antibodies represent a major barrier to successful treatment because they bind to the AAV8 capsid and neutralize the vector before it can transduce target cells [NIH, ResearchGate]. This neutralization prevents the delivery of the therapeutic transgene, often leading to the exclusion of seropositive patients from clinical trials for diseases such as Hemophilia and Pompe disease [NIH, AAPS Journal]. The prevalence of these antibodies in the general population is estimated to be between 30% and 60%, significantly limiting the reach of current AAV8-based gene therapies [Frontiers in Immunology, NIH]. To address this, researchers are developing strategies to deplete these antibodies, such as using the IgG-cleaving enzyme imlifidase (IdeS) or performing plasmapheresis [NIH, Global Genes]. Additionally, immunosuppressive regimens involving drugs like rituximab and bortezomib are being explored to prevent the formation of new antibodies or to reduce existing titers, thereby expanding the eligibility and efficacy of AAV8-based therapies [ResearchGate, CGTLive].

Other names

Anti-AAV8 antibodiesAAV8 neutralizing antibodiesAAV8 NAbAnti-AAV8 IgGPre-existing AAV8 immunity

Proteolytic cleavage of IgG, B-cell depletion, and proteasome inhibition to reduce antibody titers and enable vector transduction.