T Cell-Mediated Immune Responses to AAV and AAV Vectors
Open Access
- 13 April 2021
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Immunology
Abstract
Adeno-associated virus (AAV)-mediated gene transfer has benefited patients with inherited diseases, such as hemophilia B, by achieving long-term expression of the therapeutic transgene. Nevertheless, challenges remain due to rejection of AAV-transduced cells, which in some, but not all, patients can be prevented by immunosuppression. It is assumed that CD8+ T cells induced by natural infections with AAVs are recalled by the AAV vector’s capsid and upon activation eliminate cells expressing the degraded capsid antigens. Alternatively, it is feasible that AAV vectors, especially if given at high doses, induce de novo capsid- or transgene product-specific T cell responses. This chapter discusses CD8+ T cell responses to AAV infections and AAV gene transfer and avenues to prevent their activation or block their effector functions.Keywords
This publication has 119 references indexed in Scilit:
- Self-complementary AAVs Induce More Potent Transgene Product-specific Immune Responses Compared to a Single-stranded GenomeMolecular Therapy, 2012
- Phase 1 Gene Therapy for Duchenne Muscular Dystrophy Using a Translational Optimized AAV VectorMolecular Therapy, 2012
- Capsid-specific T-cell Responses to Natural Infections With Adeno-associated Viruses in Humans Differ From Those of Nonhuman PrimatesMolecular Therapy, 2011
- Successful attenuation of humoral immunity to viral capsid and transgenic protein following AAV-mediated gene transfer with a non-depleting CD4 antibody and cyclosporineGene Therapy, 2011
- The Complex and Evolving Story of T cell Activation to AAV Vector-encoded Transgene ProductsMolecular Therapy, 2011
- Sustained alpha‐sarcoglycan gene expression after gene transfer in limb‐girdle muscular dystrophy, type 2DAnnals of Neurology, 2010
- Impact of the Underlying Mutation and the Route of Vector Administration on Immune Responses to Factor IX in Gene Therapy for Hemophilia BMolecular Therapy, 2009
- A Preclinical Animal Model to Assess the Effect of Pre-existing Immunity on AAV-mediated Gene TransferMolecular Therapy, 2009
- mTOR regulates memory CD8 T-cell differentiationNature, 2009
- Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID Trial), a First-in-Human Phase 1/2 Clinical TrialJournal of Cardiac Failure, 2009