Study ID: AAV2-RPE65-IMM-006
Study Title: Summary of Immunogenicity Assessments from Nonclinical Studies in Canines and Non-Human Primates.

Study Report Body:
Objective: To characterize the humoral and cellular immune responses to the AAV2 capsid and the RPE65 transgene product following subretinal administration.
Methods: Serum samples from the dog and NHP studies were analyzed for anti-AAV2 and anti-RPE65 binding and neutralizing antibodies using ELISA and cell-based neutralization assays. Peripheral blood mononuclear cells (PBMCs) were analyzed for T-cell responses using an ELISPOT assay for interferon-gamma.
Results: 
- Cellular Immunity: No evidence of a significant cellular immune response (T-cell response) to either the AAV2 capsid or the RPE65 protein was identified in any NHP. 
- Humoral Immunity: Pre-existing anti-AAV2 neutralizing antibodies were low or absent in most animals prior to dosing. Following administration, a modest increase in anti-AAV2 antibody titers was observed in both species. In a few isolated cases in dogs, a transient humoral response was noted. No significant anti-RPE65 antibody responses were detected.
Conclusion: Voretigene neparvovec demonstrates a low immunogenic potential when delivered to the immune-privileged subretinal space. The observed immune responses were mild, primarily humoral, and did not correlate with any adverse clinical findings or loss of efficacy.