Journal Article

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

Pulliam, Thomas H., Laing, Kerry J., St. Germain, Russell, Eaton, Brett, Eudy, Elizabeth, Fiore-Gartland, Andrew, Jing, Lichen, Jani, Saumya, Holbrook, Michael R., Burrow, Carlissa J., Murphy, Michael, Selke, Stacy, Gittelman, Rachel M., Ford, Emily S., Wald, Anna, Ecsedi, Matyas, Bossard, Emily L., Greninger, Alexander L., Elyanow, Rebecca, Wilcox, Elise, Chapuis, Aude G., Mayer-Blackwell, Koshlan, Sholukh, Anton M., Postnikova, Elena, Koelle, David M., Xie, Hong, McClurkan, Christopher L., Robins, Harlan S.

2024

Overview

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 S ) 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 S 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 S cell clonotypes, most of which were CD8 + T cells, while also eliciting diverse T S 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 S cells provides a roadmap for the rapid assessment of T cell responses to vaccines and emerging pathogens. Koelle and colleagues use an activation marker-dependent approach to determine the recruitment of TCR by three doses of mRNA vaccination in individuals previously infected with SARS-CoV-2.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/250/1619/554/1775 / 631/250/248 / 631/250/590/2293 / 631/61/514/1949 / 692/699/255/2514 / Antibodies, Viral / Biomedical and Life Sciences / Biomedicine / CD4 antigen / CD8 antigen / CD8-Positive T-Lymphocytes / Coronaviruses / COVID-19 / COVID-19 - prevention & control / COVID-19 vaccines / Humans / Immunity / Immunological memory / Immunology / Infectious Diseases / Lymphocytes T / Memory cells / mRNA / Peripheral blood / Receptors, Antigen, T-Cell, alpha-beta - genetics / Resource / RNA, Messenger - genetics / SARS-CoV-2 / Severe acute respiratory syndrome coronavirus 2 / T cell receptors / Vaccination