AAV antibodies in people with haemophilia
Most gene therapies now undergoing clinical trials rely on a viral vector to achieve transduction of liver cells so that they produce the replacement gene. The majority of vectors are derived from adeno-associated viruses (AAV). AAVs naturally cause infection in humans, provoking an immune response that generates antibodies; individuals with AAV antibodies are ineligible for gene therapy.
UK haemophilia centres have collaborated on research to estimate the prevalence of antibodies to two AAV subtypes, 5 and 8, among 100 adults with haemophilia (Res Pract Thromb Haemost 2019;3:261-267). The overall prevalence of antibodies or inhibitors of AAV was 30% for AAV5 and 40% for AAV8, suggesting a substantial proportion of people will be ineligible for what is currently the most advanced form of gene therapy.