SARS-CoV-2 vaccination enhances the effector qualities of spike-specific T cells induced by COVID-19.
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Cai C, Gao Y, Adamo S, Rivera-Ballesteros O, Hansson L, Österborg A, Bergman P, Sandberg JK, Ljunggren H, Björkström NK, Strålin K, Llewellyn-Lacey S, Price DA, Qin C, Grifoni A, Weiskopf D, Wherry EJ, Sette A, Aleman S, Buggert M
Sci Immunol 8 (90) eadh0687 [2023-12-08; online 2023-12-08]
T cells are critical for immune protection against severe COVID-19, but it has remained unclear whether repeated exposure to SARS-CoV-2 antigens delivered in the context of vaccination fuels T cell exhaustion or reshapes T cell functionality. Here, we sampled convalescent donors with a history of mild or severe COVID-19 before and after SARS-CoV-2 vaccination to profile the functional spectrum of hybrid T cell immunity. Using combined single-cell technologies and high-dimensional flow cytometry, we found that the frequencies and functional capabilities of spike-specific CD4+ and CD8+ T cells in previously infected individuals were enhanced by vaccination, despite concomitant increases in the expression of inhibitory receptors such as PD-1 and TIM3. In contrast, CD4+ and CD8+ T cells targeting non-spike proteins remained functionally static and waned over time, and only minimal effects were observed in healthy vaccinated donors experiencing breakthrough infections with SARS-CoV-2. Moreover, hybrid immunity was characterized by elevated expression of IFN-γ, which was linked with clonotype specificity in the CD8+ T cell lineage. Collectively, these findings identify a molecular hallmark of hybrid immunity and suggest that vaccination after infection is associated with cumulative immunological benefits over time, potentially conferring enhanced protection against subsequent episodes of COVID-19.
PubMed 38064569
DOI 10.1126/sciimmunol.adh0687
Crossref 10.1126/sciimmunol.adh0687