Development of a New Off-the-Shelf Plasmacytoid Dendritic Cell–Based Approach for the Expansion and Characterization of SARS-CoV-2 Specific T Cells

We are happy to announce that our member PDC*line Pharma has publish a new scientific paper in the peer-reviewed journal “The Journal of Immunology”. Title of the article is: “Development of a New Off-the-Shelf Plasmacytoid Dendritic Cell–Based Approach for the Expansion and Characterization of SARS-CoV-2 Specific T Cells”.

The article is cohautored by  Joel Plumas in collaboration with the team of laurence chaperot from Etablissement Français Du Sang with Anthony MainoAxelle AMENLucie BouquetMarina DESCHAMPS, Olivier manches and Philippe Saas.

Abstract

Global vaccination against COVID-19 has been widely successful; however, there is a need for complementary immunotherapies in severe forms of the disease and in immunocompromised patients. Cytotoxic CD8+ T cells have a crucial role in disease control, but their function can be dysregulated in severe forms of the disease. We report here a cell-based approach using a plasmacytoid dendritic cell line (PDC*line) to expand in vitro specific CD8+ responses against COVID-19 Ags. We tested the immunogenicity of eight HLA-A*02:01 restricted peptides derived from diverse SARS-Cov-2 proteins, selected by bioinformatics analyses in unexposed and convalescent donors. Higher ex vivo frequencies of specific T cells against these peptides were found in convalescent donors compared with unexposed donors, suggesting in situ T cell expansion upon viral infection. The peptide-loaded PDC*line induced robust CD8+ responses with total amplification rates that led up to a 198-fold increase in peptide-specific CD8+ T cell frequencies for a single donor. Of note, six of eight selected peptides provided significant amplifications, all of which were conserved between SARS-CoV variants and derived from the membrane, the spike protein, the nucleoprotein, and the ORF1ab. Amplified and cloned antiviral CD8+ T cells secreted IFN-γ upon peptide-specific activation. Furthermore, specific TCR sequences were identified for two highly immunogenic Ags. Hence, PDC*line represents an efficient platform to identify immunogenic viral targets for future immunotherapies.

You can read the complete paper here