{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:01:09Z","timestamp":1792648869580,"version":"4.5.0"},"reference-count":46,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"90","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2023,12,22]]},"abstract":"<jats:p>\n            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\n            <jats:sup>+<\/jats:sup>\n            and CD8\n            <jats:sup>+<\/jats:sup>\n            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\n            <jats:sup>+<\/jats:sup>\n            and CD8\n            <jats:sup>+<\/jats:sup>\n            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-\u03b3, which was linked with clonotype specificity in the CD8\n            <jats:sup>+<\/jats:sup>\n            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.\n          <\/jats:p>","DOI":"10.1126\/sciimmunol.adh0687","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T18:58:07Z","timestamp":1702061887000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":41,"title":["SARS-CoV-2 vaccination enhances the effector qualities of spike-specific T cells induced by COVID-19"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3490-4361","authenticated-orcid":true,"given":"Curtis","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6161-3156","authenticated-orcid":true,"given":"Sarah","family":"Adamo","sequence":"additional","affiliation":[{"name":"Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6949-4270","authenticated-orcid":true,"given":"Olga","family":"Rivera-Ballesteros","sequence":"additional","affiliation":[{"name":"Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotta","family":"Hansson","sequence":"additional","affiliation":[{"name":"Department of Hematology, Karolinska University Hospital, Stockholm, Sweden."},{"name":"Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"\u00d6sterborg","sequence":"additional","affiliation":[{"name":"Department of Hematology, Karolinska University Hospital, Stockholm, Sweden."},{"name":"Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3306-3713","authenticated-orcid":true,"given":"Peter","family":"Bergman","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden."},{"name":"Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6275-0750","authenticated-orcid":true,"given":"Johan K.","family":"Sandberg","sequence":"additional","affiliation":[{"name":"Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Gustaf","family":"Ljunggren","sequence":"additional","affiliation":[{"name":"Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0967-076X","authenticated-orcid":true,"given":"Niklas K.","family":"Bj\u00f6rkstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8801-3169","authenticated-orcid":true,"given":"Kristoffer","family":"Str\u00e5lin","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden."},{"name":"Department of Medicine Huddinge, Infectious Diseases, Karolinska Institutet, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4703-0413","authenticated-orcid":true,"given":"Sian","family":"Llewellyn-Lacey","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Cardiff University School of Medicine, University Hospital of Wales, Cardiff, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9416-2737","authenticated-orcid":true,"given":"David A.","family":"Price","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Cardiff University School of Medicine, University Hospital of Wales, Cardiff, UK."},{"name":"Systems Immunity Research Institute, Cardiff University School of Medicine, University Hospital of Wales, Cardiff, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6261-1232","authenticated-orcid":true,"given":"Chuan","family":"Qin","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China."},{"name":"National Health Commission Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2209-5966","authenticated-orcid":true,"given":"Alba","family":"Grifoni","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2968-7371","authenticated-orcid":true,"given":"Daniela","family":"Weiskopf","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA."},{"name":"Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, San Diego, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0477-1956","authenticated-orcid":true,"given":"E. John","family":"Wherry","sequence":"additional","affiliation":[{"name":"Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA."},{"name":"Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA."},{"name":"Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7013-2250","authenticated-orcid":true,"given":"Alessandro","family":"Sette","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA."},{"name":"Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, San Diego, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0461-4870","authenticated-orcid":true,"given":"Soo","family":"Aleman","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden."},{"name":"Department of Medicine Huddinge, Infectious Diseases, Karolinska Institutet, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0633-1719","authenticated-orcid":true,"given":"Marcus","family":"Buggert","sequence":"additional","affiliation":[{"name":"Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100312"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01184-4"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.7326\/M21-4130"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00143-8"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00801-5"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00271-7"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.08.001"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01175-5"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00827"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109414"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.05.002"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2100446"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0944-y"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abe4782"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.07.005"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm0829"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.03.018"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2035"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.08.009"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2116414"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103705"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00320-6"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.05.022"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abl5344"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2021.101505"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004251"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-041015-055318"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.017"},{"key":"e_1_3_2_30_2","first-page":"147","article-title":"SARS-CoV-2 viral load and shedding kinetics","volume":"21","author":"Puhach O.","year":"2023","unstructured":"O. 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