High-throughput screening of patient sera for pre-existing AAV vector antibodies
Pre-existing neutralizing antibodies (nAbs) pose a serious barrier to safe and effective gene therapy use. It has been reported that approximately 70% of adults have sera antibodies for AAVs (adeno-associated viruses) and memory T cells . A recent study investigated the prevalence of nAbs against AAV-1, -2, -5, and -8 in blood samples from healthy donors. The results were troubling as they found that 47-74% of samples had AAV-2 nAbs even though low titers can block in vivo transduction .
Though viral genomic material has been removed, the capsid carrying the therapeutic payload can trigger an immune response. Prior viral exposure can lead to undesired humoral and/or T cell-mediated immunity that will be reactivated upon vector delivery [29-32].