Differential T cell immune responses to deamidated adeno-associated virus vector

Differential T cell immune responses to deamidated adeno-associated virus vector

Blog Article

Despite the high safety profile demonstrated in clinical trials, the immunogenicity of adeno-associated virus (AAV)-mediated gene therapy remains a major hurdle.Specifically, T-cell-mediated immune responses to AAV vectors are related to loss of efficacy and potential liver toxicities.As post-translational modifications in T cell epitopes have the potential to affect Mugs/Cups/Tumblers immune reactions, the cellular immune responses to peptides derived from spontaneously deamidated AAV were investigated.Here, we report that highly deamidated sites in AAV9 contain CD4 T cell epitopes with a Th1 cytokine pattern in multiple human donors with diverse human leukocyte antigen (HLA) backgrounds.Furthermore, some Clothing peripheral blood mononuclear cell (PBMC) samples demonstrated differential T cell activation to deamidated or non-deamidated epitopes.

Also, in vitro and in silico HLA binding assays showed differential binding to the deamidated or non-deamidated peptides in some HLA alleles.This study provides critical attributes to vector-immune-mediated responses, as AAV deamidation can impact the immunogenicity, safety, and efficacy of AAV-mediated gene therapy in some patients.