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Nat Immunol . Repeated mRNA vaccination sequentially boosts SARS-CoV-2-specific CD8+ T cells in persons with previous COVID-19

tetano

Editor, Senior Moderator
Nat Immunol


. 2023 Dec 6.
doi: 10.1038/s41590-023-01692-x. Online ahead of print. Repeated mRNA vaccination sequentially boosts SARS-CoV-2-specific CD8[SUP]+[/SUP] T cells in persons with previous COVID-19

Emily S Ford[SUP] #[/SUP][SUP] 1 2 [/SUP], Koshlan Mayer-Blackwell[SUP] #[/SUP][SUP] 2 [/SUP], Lichen Jing[SUP] #[/SUP][SUP] 1 [/SUP], Kerry J Laing[SUP] 1 [/SUP], Anton M Sholukh[SUP] 2 [/SUP], Russell St Germain[SUP] 2 [/SUP], Emily L Bossard[SUP] 2 [/SUP], Hong Xie[SUP] 3 [/SUP], Thomas H Pulliam[SUP] 1 [/SUP], Saumya Jani[SUP] 1 3 [/SUP], Stacy Selke[SUP] 3 [/SUP], Carlissa J Burrow[SUP] 1 [/SUP], Christopher L McClurkan[SUP] 1 [/SUP], Anna Wald[SUP] 1 2 3 4 [/SUP], Alexander L Greninger[SUP] 2 3 [/SUP], Michael R Holbrook[SUP] 5 [/SUP], Brett Eaton[SUP] 5 [/SUP], Elizabeth Eudy[SUP] 5 [/SUP], Michael Murphy[SUP] 5 [/SUP], Elena Postnikova[SUP] 5 [/SUP], Harlan S Robins[SUP] 6 [/SUP], Rebecca Elyanow[SUP] 6 [/SUP], Rachel M Gittelman[SUP] 6 7 [/SUP], Matyas Ecsedi[SUP] 8 9 [/SUP], Elise Wilcox[SUP] 8 [/SUP], Aude G Chapuis[SUP] 1 8 [/SUP], Andrew Fiore-Gartland[SUP] 2 [/SUP], David M Koelle[SUP] 10 11 12 13 14 [/SUP]



Affiliations
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hybrid immunity is more protective than vaccination or previous infection alone. To investigate the kinetics of spike-reactive T (T[SUB]S[/SUB]) cells from SARS-CoV-2 infection through messenger RNA vaccination in persons with hybrid immunity, we identified the T cell receptor (TCR) sequences of thousands of index T[SUB]S[/SUB] cells and tracked their frequency in bulk TCRβ repertoires sampled longitudinally from the peripheral blood of persons who had recovered from coronavirus disease 2019 (COVID-19). Vaccinations led to large expansions in memory T[SUB]S[/SUB] cell clonotypes, most of which were CD8[SUP]+[/SUP] T cells, while also eliciting diverse T[SUB]S[/SUB] cell clonotypes not observed before vaccination. TCR sequence similarity clustering identified public CD8[SUP]+[/SUP] and CD4[SUP]+[/SUP] TCR motifs associated with spike (S) specificity. Synthesis of longitudinal bulk ex vivo single-chain TCRβ repertoires and paired-chain TCRɑβ sequences from droplet sequencing of T[SUB]S[/SUB] cells provides a roadmap for the rapid assessment of T cell responses to vaccines and emerging pathogens.


 
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