January 20, 2021 Journal article Open Access

Vandamme Céline; Xicluna Rebecca; Hesnard Leslie; Devaux Marie; Jaulin Nicolas; Guilbaud Mickaël; Le Duff Johanne; Couzinié Célia; Moullier Philippe; Saulquin Xavier; Adjali Oumeya

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    "description": "<p><strong>Abstract</strong></p>\n\n<p>Pre-existing immunity to AAV capsid may compromise the safety and efficiency of rAAV-mediated gene transfer in patients. Anti-capsid cytotoxic immune responses have proven to be a challenge to characterize because of the scarcity of circulating AAV-specific CD8+&nbsp;T lymphocytes which can seldom be detected with conventional flow cytometry or ELISpot assays. Here, we used fluorescent MHC class I tetramers combined with magnetic enrichment to detect and phenotype AAV8-specific CD8+&nbsp;T cells in human PBMCs without prior amplification. We showed that all healthy individuals tested carried a pool of AAV8-specific CD8+&nbsp;T cells with a CD45RA+CCR7&minus;&nbsp;terminally-differentiated effector memory cell (TEMRA) fraction.&nbsp;<em>Ex vivo</em>&nbsp;frequencies of total AAV-specific CD8+&nbsp;T cells were not predictive of IFN&gamma; ELISpot responses but interestingly we evidenced a correlation between the proportion of TEMRA&nbsp;cells and IFN&gamma; ELISpot positive responses. TEMRA&nbsp;cells may then play a role in recombinant AAV-mediated cytotoxicity in patients with preexisting immunity. Overall, our results encourage the development of new methods combining increased detection sensitivity of AAV-specific T cells and their poly-functional assessment to better characterize and monitor AAV capsid-specific cellular immune responses in the perspective of rAAV-mediated clinical trials.</p>", 
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    "title": "Tetramer-Based Enrichment of Preexisting Anti-AAV8 CD8+ T Cells in Human Donors Allows the Detection of a TEMRA Subpopulation", 
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      "title": "Frontiers in Immunology"
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        "title": "Unlocking Precision Gene Therapy", 
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        "affiliation": "INSERM UMR 1089, Universit\u00e9 de Nantes, CHU de Nantes, Nantes, France", 
        "name": "Vandamme\u00a0C\u00e9line"
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        "affiliation": "INSERM UMR 1089, Universit\u00e9 de Nantes, CHU de Nantes, Nantes, France", 
        "name": "Xicluna Rebecca"
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      {
        "affiliation": "CRCINA, INSERM, CNRS, Universit\u00e9 d'Angers, Universit\u00e9 de Nantes, Nantes, France", 
        "name": "Hesnard Leslie"
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        "affiliation": "INSERM UMR 1089, Universit\u00e9 de Nantes, CHU de Nantes, Nantes, France", 
        "name": "Devaux Marie"
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        "affiliation": "INSERM UMR 1089, Universit\u00e9 de Nantes, CHU de Nantes, Nantes, France", 
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        "affiliation": "INSERM UMR 1089, Universit\u00e9 de Nantes, CHU de Nantes, Nantes, France", 
        "name": "Guilbaud Micka\u00ebl"
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        "affiliation": "INSERM UMR 1089, Universit\u00e9 de Nantes, CHU de Nantes, Nantes, France", 
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        "affiliation": "INSERM UMR 1089, Universit\u00e9 de Nantes, CHU de Nantes, Nantes, France", 
        "name": "Couzini\u00e9 C\u00e9lia"
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        "affiliation": "INSERM UMR 1089, Universit\u00e9 de Nantes, CHU de Nantes, Nantes, France", 
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        "affiliation": "CRCINA, INSERM, CNRS, Universit\u00e9 d'Angers, Universit\u00e9 de Nantes, Nantes, France", 
        "name": "Saulquin Xavier"
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        "affiliation": "INSERM UMR 1089, Universit\u00e9 de Nantes, CHU de Nantes, Nantes, France", 
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