{"doi":"10.1126/sciimmunol.adh0687","title":"SARS-CoV-2 vaccination enhances the effector qualities of spike-specific T cells induced by COVID-19","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.","journal":"Science Immunology","year":2023,"id":323182,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":38,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":501133,"name":"Yu Gao","orcid":"0000-0002-4615-3614","position":1,"is_corresponding":false},{"id":1030737,"name":"Sarah Adamo","orcid":"0000-0002-6161-3156","position":2,"is_corresponding":false},{"id":104826,"name":"Olga Rivera‐Ballesteros","orcid":"0000-0001-6949-4270","position":3,"is_corresponding":false},{"id":650096,"name":"Lotta Hansson","orcid":"0000-0001-6614-5737","position":4,"is_corresponding":false},{"id":233538,"name":"Anders Österborg","orcid":"0000-0001-6489-4865","position":5,"is_corresponding":false},{"id":312380,"name":"Peter Bergman","orcid":"0000-0003-3306-3713","position":6,"is_corresponding":false},{"id":104894,"name":"Johan K. 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