Low cross reactivity between wild type and deamidated AAV can lead to false negative results in immune monitoring T-cell assays.

ABSTRACT: During gene therapy trials, immune responses against adeno-associated virus (AAV) vectors are monitored by antibody assays that detect the humoral and T-cell mediated cellular responses to AAV vectors. T cell assays commonly utilize the collection of patients' peripheral blood mononuclear cells (PBMCs) and stimulation with AAV-derived overlapping peptides. We recently described that spontaneous deamidation coincides with T cell epitopes in AAV capsids and that spontaneous deamidation may enhance or decrease immunogenicity in some individuals. This raised the concern for false negative results of antibody detection and PBMC immune monitoring assays because these assays use wild-type (WT) AAV or WT peptides for T cell re-stimulation and these peptides may not re-activate T cells that were st

SUBMITTER: Bing SJ 

PROVIDER: S-EPMC10352612 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature