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Development of a Chemiluminescent ELISA Method for the Detection of Total Anti-Adeno Associated Virus Serotype 9 (AAV9) Antibodies. | LitMetric

AI Article Synopsis

  • Recombinant adeno-associated viruses (rAAV) are crucial for gene therapy delivery due to their safety and effectiveness, but preexisting anti-AAV antibodies in humans can hinder therapeutic success by neutralizing the viral particles.
  • Cell-based reporter assays currently assess the level of neutralizing antibodies but are time-consuming and vary in reliability; in contrast, enzyme-linked immunosorbent assays (ELISAs) offer a simpler and more efficient alternative.
  • This study developed a sensitive chemiluminescent ELISA to detect anti-AAV9 antibodies and found a strong correlation between total anti-AAV9 antibodies and neutralizing antibodies in heart disease patients, suggesting that ELISA could effectively screen and exclude subjects in future clinical studies.

Article Abstract

Recombinant adeno associated viruses (rAAV) have become an important tool for the delivery of gene therapeutics due to long-standing safety and success in clinical trials. Since humans often become exposed to AAVs and develop anti-AAV antibodies (Abs), a potential impediment to the success of gene therapeutics is neutralization of the viral particle before it has had a chance to bind and enter target cells to release the transgene. Identification of subjects with preexisting Abs having neutralizing potential, and exclusion of such subjects from clinical studies is expected to enhance drug efficacy. cell-based reporter assays are most often employed to determine the level of neutralizing antibodies in a given population. Such assays measure the ability of the Abs to prevent viral binding and entry into cells by engaging epitopes on the viral capsid involved in host cell receptor binding. In general, cell-based assays are low throughput and labor intensive and may suffer from high variability and low sensitivity issues. In contrast, enzyme-linked immunosorbent assays (ELISAs) are simpler, less variable, and have higher throughput. Demonstrating a correlation between neutralizing Abs assessed by a cell-based assay and total binding Abs measured in an ELISA will enable the use and substitution of the latter for screening and exclusion of subjects. In this work, we describe the development of a highly sensitive, specific, robust, and reproducible chemiluminescent ELISA method for the detection of total anti-AAV9 Abs. Using this method, we analyzed the prevalence of preexisting anti-AAV9 Abs in 100 serum samples from heart disease patients. Analysis of neutralizing Abs in the same samples using an cell-based assay showed a strong correlation between total anti-AAV9 Abs and neutralizing Abs, indicating the feasibility of using the total Ab ELISA in the future for patient screening and exclusion.

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Source
http://dx.doi.org/10.1089/hgtb.2018.131DOI Listing

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