| Autor: |
Emily S. Ford, Koshlan Mayer-Blackwell, Lichen Jing, Anton M. Sholukh, Russell St. Germain, Emily L. Bossard, Hong Xie, Thomas H. Pulliam, Saumya Jani, Stacy Selke, Carlissa J. Burrow, Christopher L. McClurkan, Anna Wald, Michael R. Holbrook, Brett Eaton, Elizabeth Eudy, Michael Murphy, Elena Postnikova, Harlan S. Robins, Rebecca Elyanow, Rachel M. Gittelman, Matyas Ecsedi, Elise Wilcox, Aude G. Chapuis, Andrew Fiore-Gartland, David M. Koelle |
| Rok vydání: |
2022 |
| DOI: |
10.21203/rs.3.rs-2146712/v1 |
| Popis: |
Almost three years into the SARS-CoV-2 pandemic, hybrid immunity is highly prevalent worldwide and more protective than vaccination or prior infection alone. Given emerging resistance of variant strains to neutralizing antibodies (nAb), it is likely that T cells contribute to this protection. To understand how sequential SARS-CoV-2 infection and mRNA-vectored SARS-CoV-2 spike (S) vaccines affect T cell clonotype-level expansion kinetics, we identified and cross-referenced TCR sequences from thousands of S-reactive single cells against deeply sequenced peripheral blood TCR repertoires longitudinally collected from persons during COVID-19 convalescence through booster vaccination. Successive vaccinations recalled memory T cells and elicited antigen-specific T cell clonotypes not detected after infection. Vaccine-related recruitment of novel clonotypes and the expansion of S-specific clones were most strongly observed for CD8+ T cells. Severe COVID-19 illness was associated with a more diverse CD4+ T cell response to SARS-CoV-2 both prior to and after mRNA vaccination, suggesting imprinting of CD4+ T cells by severe infection. TCR sequence similarity search algorithms revealed myriad public TCR clusters correlating with human leukocyte antigen (HLA) alleles. Selected TCRs from distinct clusters functionally recognized S in the predicted HLA context, with fine viral peptide requirements differing between TCRs. Most subjects tested had S-specific T cells in the nasal mucosa after a 3rd mRNA vaccine dose. The blood and nasal T cell responses to vaccination revealed by clonal tracking were more heterogeneous than nAb boosts. Analysis of bulk and single cell TCR sequences reveals T cell kinetics and diversity at the clonotype level, without requiring prior knowledge of T cell epitopes or HLA restriction, providing a roadmap for rapid assessment of T cell responses to emerging pathogens. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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