High Concordance of Total Antibody and Transduction Inhibition Assays Enables Replacement of Cell-Based Antibody Testing for Preexisting Anti-AAV Immunity in Cynomolgus Monkey.

Abstract

Testing for preexisting anti-AAV immunity in non-human primates constitutes an essential part of screening procedures for nonclinical studies with gene therapy, which is customary performed using transduction inhibition (TI) assays. These assays cause high costs and a significant operational burden owing to their complexity and low throughput. However, broader implementation of more practical total antibody assays (TAb) is hindered by the lack of conclusive data demonstrating assays comparability in non-human primates. To determine whether TAb assays can serve as a viable alternative to TI assays for anti-AAV screening in monkeys, we conducted a comparative study for two AAV serotypes (AAV2 and AAV9), with tailored specificity control measures incorporated in both assay formats. Both the TI and TAb assays showed a high concordance in detection of preexisting anti-AAV immunity in cynomolgus monkey. The presented TAb assay offers a simple, cost- and time-saving alternative to TI assays for pre-study testing of non-human primates. The use of such TAb assays can thus result in concordant animal enrollment at lower cost and greater speed as compared to TI-based screening tests.