Longitudinal characterization of CD8+ T cells recognizing a dominant epitope of SARS-CoV-2 spike protein in COVID-19 vaccinated and infected individuals

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Abstract COVID-19, caused by SARS-CoV-2 infection, sparked an ongoing global pandemic. While cell-mediated immunity is crucial in mitigating the severity and eradicating viral infections, a comprehensive characterization of CD8+ T cell antigen-specificity, frequency, proliferative capacity, and TCR sequences against SARS-CoV-2 in both COVID-19 vaccinated and recovered adults remains incomplete. In this study, we embark on a longitudinal analysis of circulating CD8+ T cells targeting 10 epitopes from the SARS-CoV-2 spike (S) protein across multiple visits from donors spanning three and a half years. Utilizing multi-color flow cytometry with antigen-specific tetramers, we observed frequencies of circulating CD8+ T cells ranging from undetectable to 1% in HLA-A2+ vaccinated and infected individuals. Notably, we did not observe significant differences in spike-specific CD8+ T cell frequencies between vaccinated and infected donors. However, among vaccinated donors, we noted a decline over time in central memory T cells specific to a dominant S protein epitope, S-YLQ (S-269-277, YLQPRTFLL). Our in vitro stimulation assays revealed robust expansion of CD8+ T cells, both in percentage and magnitude, against the S-YLQ epitope compared to other epitopes in infected and vaccinated individuals. Analysis of longitudinal follow-up data spanning three years is ongoing.

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