A Single Neutralizing Antibody Assay for Detection of Anti-AAV9 Antibodies in Minipig and Human Serum

Purpose

The field of gene therapy has grown significantly in the last decade with Adeno-Associated Virus (AAV)-based therapeutics becoming a common vector for this modality. A critical component of designing effective preclinical strategies for AAV-based therapeutics is evaluating pre-existing anti-AAV antibodies as these can have a major impact on translatability of preclinical data. Monitoring strategies for this include screening animals with neutralizing antibody (NAb) immunoassays for animal selection or stratification. Minipigs are useful alternatives to rodents for preclinical studies due to their physiological similarity to humans, and their utility for AAV therapeutic testing is well established. Assays that easily translate between preclinical species such as minipigs to humans in clinical testing can save time and resources for programs. To this end, we describe an AAV9 NAb assay that can be utilized across species. This versatile assay provides a rapidly implemented screening solution for use with both minipig serum samples and human serum samples.