Repeated MRNA Vaccination Sequentially Boosts SARS-CoV-2-specific CD8 T Cells in Persons with Previous COVID-19

Overview

Journal Nat Immunol

Date 2023 Dec 6

PMID 38057617

Authors

Emily S Ford

Koshlan Mayer-Blackwell

Lichen Jing

Kerry J Laing

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

Alexander L Greninger

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

Affiliations

Soon will be listed here.

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) 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 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 cell clonotypes, most of which were CD8 T cells, while also eliciting diverse T cell clonotypes not observed before vaccination. TCR sequence similarity clustering identified public CD8 and CD4 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 cells provides a roadmap for the rapid assessment of T cell responses to vaccines and emerging pathogens.

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