Neutralizing antibody against adeno-associated virus (AAV) serotype

Neutralizing antibodies against adeno-associated virus (AAV) serotypes are immunoglobulins produced by the host immune system—either from previous natural exposure to wild-type AAV or from cross-reactive infections—that bind and neutralize AAV vectors used in gene therapy. The presence of these antibodies is a major limiting factor for the efficacy of AAV-mediated gene transfer: they can block AAV vector entry into target cells and promote clearance by the immune system. The prevalence of these neutralizing antibodies varies widely among populations and serotypes; for example, studies have shown high rates of seropositivity to AAV2, and significant rates to AAV1, AAV6, AAV8, and AAV9. These antibodies represent a significant immunological barrier, requiring pre-screening of patients for eligibility in AAV-based gene therapy trials and motivating the development of novel capsids with reduced antibody recognition, immune evasion strategies, and patient desensitization protocols.

Other names

Anti-AAV neutralizing antibodyPre-existing AAV antibodyAAV serotype-neutralizing antibody

Bind and neutralize AAV particles, block uptake into target cells, prevent successful gene delivery