AAV vectors trigger innate immune pathways

New Rochelle, NY, July 10, 2024—Adeno-associated virus (AAV)-based viral vectors used in human gene therapy can trigger innate immune pathways, leading to the initiation of adaptive immune responses. A new Review article published in the peer-reviewed journal Human Gene Therapy describes the range of likely redundant innate immune pathways that AAV vectors can activate, resulting in an exaggerated adaptive immune response. Click here to read the article now.

Roland Herzog, PhD and Sandeep Kumar, PhD, from Indiana University, and coauthors describe innate immunity and the sensing of viral vectors, including sensing of the viral genome via toll-like receptor 9 and toll-like receptor 2 as a sensor of capsid. They also discuss the role of interleukin-1-receptor-1 in B and T cell activation, cytoplasmic DNA sensors, and cytoplasmic RNA sensors. The review article continues with a discussion of cells that mediate innate sensing, immunity, and the transition to adaptive CD8+ T cell responses. Additional topics include innate signals leading to B cell activation and complement activation.

The authors conclude that “Although AAV vectors contain weaker inflammatory signals than many other viruses or vector systems, they nonetheless elicit innate responses that can have a significant impact on gene therapy.”

“Immune responses to AAV vectors have emerged as an important safety concern in human gene therapy trials,” says Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School. “Understanding the complex biologic mechanisms that underlie the adverse reactions is the key to overcoming them. This review article nicely summarizes how AAV can trigger specific innate immune pathways.”

About the Journal
Human Gene Therapy, the Official Journal of the European Society of Gene and Cell Therapy and eight other international gene therapy societies, was the first peer-reviewed journal in the field and provides all-inclusive access to the critical pillars of human gene therapy: research, methods, and clinical applications. The Journal is led by Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Chan Medical School, and an esteemed international editorial board. Human Gene Therapy is available in print and online. Complete tables of contents and a sample issue are available on the Human Gene Therapy website.

About the Publisher
Mary Ann Liebert, Inc. is a global media company dedicated to creating, curating, and delivering impactful peer-reviewed research and authoritative content services to advance the fields of biotechnology and the life sciences, specialized clinical medicine, and public health and policy. For complete information, please visit the Mary Ann Liebert, Inc. website.