Optimizing AAV gene therapy: Preclinical insights on antibody prevalence in cynomolgus macaques

Gene therapy using AAV vectors is rapidly advancing, but preexisting immunity in terrestrial species remains a critical barrier to successful transduction. Neutralizing antibodies can reduce vector efficacy, alter biodistribution, and trigger immune responses, jeopardizing clinical outcomes.

AAV vectors are widely used for gene delivery due to their safety and tissue tropism. However, natural exposure to wild-type AAV leads to antibody formation in humans and in nonhuman primates (NHPs). NABs block vector entry, while TABs may activate complementary pathways. It is well established that seroprevalence varies by serotype, geography, and assay type, complicating preclinical study design. Even though Cynomolgus macaques are the gold standard for gene therapy safety and biodistribution studies, robust serostatus data for these models has been limited in the literature to date. Recently, Labcorp scientists helped to close this translational gap with a study published in the February 2026 issue of Human Gene Therapy evaluating NAB and TAB antibody seropositivity in this important model.

Results

Seroprevalence of AAV antibodies in cynomolgus macaques

Figure 1. Seroprevalence (seropositivity) of antibodies against AAV serotypes in cynomolgus macaques. NAB (Asian): AAV2 (71%), AAV5 (21%), AAV8 (88%), AAV9 (69%). NAB (Mauritian): AAV5 (13%). TAB (Mauritian): AAV2 (51%), AAV8 (53%), AAV9 (58%). This visualization highlights the low prevalence of AAV5 antibodies and the high prevalence of AAV2, AAV8, and AAV9, reinforcing the need for prescreening in preclinical studies.

Conclusion

Preexisting immunity to AAV vectors is a major challenge for gene therapy development. Our findings confirm high seroprevalence for AAV2, AAV8, and AAV9 in cynomolgus macaques, emphasizing the need for rigorous prescreening. Labcorp offers comprehensive immunogenicity testing platforms, including NAB and TAB assays, across multiple species supporting human clinical trial monitoring and companion diagnostics. Labcorp’s NAB and TAB testing solutions also enable precise animal selection, minimizing risk and supporting translational relevance. By leveraging these capabilities across both preclinical and clinical studies, sponsors can accelerate timelines, improve therapeutic success, and ultimately deliver transformative treatments to patients worldwide.