Global seroprevalence of neutralizing and total antibodies against AAV vectors and their impact on the clinical gene therapy landscape: a scoping review

The study analyzed the global prevalence of neutralizing and total antibodies against adeno-associated viruses (AAV), which represent a major barrier to clinical application of AAV-based gene therapy. The research included 50 studies published between 1968 and 2026 and 222 clinical trials registered in ClinicalTrials.gov. The most frequently studied serotypes were AAV2, AAV8, and AAV5. Seroprevalence consistently increased with age and varied by geographic region, although limited data from Africa and Latin America prevents robust regional conclusions. The median number of trial participants was 14 individuals, and neutralizing antibody exclusion criteria significantly reduce the number of eligible patients. Long-term follow-up showed that declining transgene expression is often associated with capsid-directed immune response. The study recommends standardized serological assays and immunomodulatory strategies to improve gene therapy efficacy.