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

نویسندگان

چکیده

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 to AAV vectors. T cell commonly utilize collection of patients’ peripheral blood mononuclear cells (PBMCs) stimulation with AAV-derived overlapping peptides. We recently described spontaneous deamidation coincides epitopes in capsids may enhance or decrease immunogenicity some individuals. This raised concern for false negative results detection PBMC monitoring because these use wild-type (WT) WT peptides re-stimulation not re-activate were stimulated deamidated capsid. To investigate this concern, we modeled scenario expanding evaluated cross-reactivity expanded In majority samples, restimulated peptide had significantly lowered IL-2 IFN-γ production. Spiking four pool used re-stimulation, restored signal corrected performance assay. also impact on anti binding antibodies did observe a major seroprevalence AAV9. These data indicate high level result underestimation even failure during monitoring.

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ژورنال

عنوان ژورنال: Frontiers in Immunology

سال: 2023

ISSN: ['1664-3224']

DOI: https://doi.org/10.3389/fimmu.2023.1211529