SARS-CoV-2 vaccination enhances the effector qualities of spike-specific T cells induced by COVID-19

Cai, Curtis, Gao, Yu, Adamo, Sarah, Rivera-Ballesteros, Olga, Hansson, Lotta, Österborg, Anders, Bergman, Peter, Sandberg, Johan K., Ljunggren, Hans-Gustaf, Björkström, Niklas K., Strålin, Kristoffer, Llewellyn-Lacey, Sian, Price, David A. ORCID: https://orcid.org/0000-0001-9416-2737, Qin, Chuan, Grifoni, Alba, Weiskopf, Daniela, Wherry, E. John, Sette, Alessandro, Aleman, Soo and Buggert, Marcus 2023. SARS-CoV-2 vaccination enhances the effector qualities of spike-specific T cells induced by COVID-19. Science Immunology 8 (90) 10.1126/sciimmunol.adh0687

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	American Association for the Advancement of Science
ISSN:	2470-9468
Date of First Compliant Deposit:	25 January 2024
Date of Acceptance:	31 October 2023
Last Modified:	02 Feb 2024 05:51
URI:	https://orca.cardiff.ac.uk/id/eprint/165826

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