Highly Networked SARS-CoV-2 Peptides Elicit T Cell Responses with Enhanced Specificity.

ImmunoHorizons 2023 Jun 01

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Identifying SARS-CoV-2-specific T cell epitope-derived peptides is critical for the development of effective vaccines and measuring the duration of specific SARS-CoV-2 cellular immunity. In this regard, we previously identified T cell epitope-derived peptides within topologically and structurally essential regions of SARS-CoV-2 spike and nucleocapsid proteins by applying an immunoinformatics pipeline. In this study, we selected 30 spike- and nucleocapsid-derived peptides and assessed whether these peptides induce T cell responses and avoid major mutations found in SARS-CoV-2 variants of concern. Our peptide pool was highly specific, with only a single peptide driving cross-reactivity in people unexposed to SARS-COV-2, and immunogenic, inducing a polyfunctional response in CD4+ and CD8+ T cells from COVID-19 recovered individuals. All peptides were immunogenic and individuals recognized broad and diverse peptide repertoires. Moreover, our peptides avoided most mutations/deletions associated with all four SARS-CoV-2 variants of concern while retaining their physicochemical properties even when genetic changes are introduced. This study contributes to an evolving definition of individual CD4+ and CD8+ T cell epitopes that can be used for specific diagnostic tools for SARS-CoV-2 T cell responses and is relevant to the development of variant-resistant and durable T cell-stimulating vaccines. Copyright © 2023 The Authors.

Citation

Gabriel Duette, Eunok Lee, Gabriela Martins Costa Gomes, Katie Tungatt, Chloe Doyle, Vicki V Stylianou, Ashley Lee, Susan Maddocks, Janette Taylor, Rajiv Khanna, Rowena A Bull, Marianne Martinello, Kerrie J Sandgren, Anthony L Cunningham, Sarah Palmer. Highly Networked SARS-CoV-2 Peptides Elicit T Cell Responses with Enhanced Specificity. ImmunoHorizons. 2023 Jun 01;7(6):508-527