Medical Virology. 2022 May 16
Hubert D.-J Daniel, Sanjay Kumar, Rajesh Kannangai, Farzana J., Joseph N. Joel, Aby Abraham, Kavitha M. Lakshmi, Mavis Agbandje-McKenna, Kirsten E. Coleman, Arun Srivastava, Alok Srivastava, Asha M. Abraham
Products used in the paper Details Operation
AAV vector packaging The AAV3 vector used in this study for screening NAb carried the gene coding for mCherry driven by a cytomegalovirus promoter. Purified AAV3 vectors were procured from PackGene Biotech LLC. Request Quote

Research Field: hemophilia A

Keywords: AAV3, age-stratified, hemophilia A, total capsid-binding antibody

AAV Serotype: AAV3

Animal or cell line strain: COS‐7 cells

Abstract

Gene therapy using an adeno-associated virus (AAV) vector offers a new treatment option for individuals with monogenetic disorders. The major bottleneck is the presence of pre-existing anti-AAV antibodies, which impacts its use. Even very low titers of neutralizing antibodies (NAb) to capsids from natural AAV infections have been reported to inhibit the transduction of intravenously administered AAV in animal models and are associated with limited efficacy in human trials. Assessing the level of pre-existing NAb is important for determining the primary eligibility of patients for AAV vector-based gene therapy clinical trials. Techniques used to screen AAV-antibodies include AAV capsid enzyme-linked immunosorbent assay (ELISA) and transduction inhibition assay (TIA) for detecting total capsid-binding (TAb) and Nab, respectively. In this study, we screened 521 individuals with hemophilia A from India for TAb and NAb using ELISA and TIA, respectively. The prevalence of TAb and NAb in hemophilia A patients from India were 96% and 77.5%, respectively. There was a significant increase in anti-AAV3 NAb prevalence with age in the hemophilia A patient group from India. There was a trend in anti-AAV3 TAb positivity between the pediatric age group (94.4%) and the adult age group (97.4%).

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