Preclinical Assessment of Antibody Responses to Adeno-Associated Virus (AAV) Vector-Based Capsids of AAV2,AAV5,AAV8,or AAV9 in Laboratory Cynomolgus Macaques ( Macaca fascicularis ) of Asian or Mauritian Origin
Restricted accessResearch articleFirst published online February, 2026
Preclinical Assessment of Antibody Responses to Adeno-Associated Virus (AAV) Vector-Based Capsids of AAV2,AAV5,AAV8,or AAV9 in Laboratory Cynomolgus Macaques ( Macaca fascicularis ) of Asian or Mauritian Origin
Adeno-associated virus (AAV)-based vectors are the most commonly used vectors for gene therapy. Wild-type AAV infections occur widely in humans and nonhuman primates (NHPs), and an accurate assessment of preexisting AAV antibodies is crucial for the efficient use of AAV-based gene therapies in preclinical and clinical studies. Cynomolgus macaques (Macaca fascicularis) are well-established preclinical large animal models for evaluating the efficacy and safety of AAV-mediated gene therapies intended for human use. We provide a retrospective evaluation comparing preexisting AAV-neutralizing or total antibody titers against serotypes AAV2, AAV5, AAV8, or AAV9 in cynomolgus macaque cohorts of Asian or Mauritian origin. We used an in vitro neutralizing antibody (NAB) assay to detect NAB titers or an in vitro Meso Scale Discovery-based assay for the quantification of total binding antibodies (TABs) in blood samples. Results were obtained to measure the serostatus of animals. In our analysis, the in vitro NAB assay revealed the lowest seroprevalence for AAV5 (13 ± 15% to 21 ± 6%) independent of origin. In the same assay, Asian animals were highly seropositive against AAV8, followed by AAV2 and AAV9 serotypes (88 ± 13%, 71 ± 10%, 69 ± 9%, respectively). Whereby, the prevalence of seropositivity was lower in animals of Mauritian origin with the highest seroprevalence for AAV9 (58 ± 7%), followed by AAV8 (53 ± 17%) and AAV2 (51 ± 20%) assessed by in vitro TAB assay. Notably, co-prevalences of antibody responses against AAV2, AAV8, and AAV9 serotypes resulted in 39.8% seropositivity (in vitro NAB assay) in NHPs of Asian and in about 32.6% (in vitro TAB assay) of Mauritian origin.
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