{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T19:29:40Z","timestamp":1785439780978,"version":"3.56.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The long-term dynamics of T-cell immunity following SARS-CoV-2 vaccination, essential for durable protection, remain incompletely understood. This study, therefore, aimed to investigate the kinetics and persistence of spike-specific T-cell responses in vaccinated healthcare workers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Within the framework of the ORCHESTRA Project, we conducted a longitudinal study on the kinetics and persistence of CD4+ and CD8+ T cell immunity in healthcare workers (n=305) from four hospitals and public health centers across two European countries who received either 2 or 3 doses of an mRNA vaccine, with or without prior SARS-CoV-2 infection. Specifically, the anti-spike adaptive immune cellular response was evaluated, focusing on its crosstalk with the B cell response as measured by serology. Circulating cellular adaptive immune cells were extensively analyzed using flow cytometry to assess pro-inflammatory cytokine production (TNF-\u03b1, IFN-\u03b3, IL-2), functional activation (CD154), and memory differentiation (CD45RO).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our findings show that anti-spike T cell reactivity is not influenced by age, with the only exception of a weak positive correlation with spike-specific CD8+CD45RO+ T lymphocytes (Spearman\u2019s rho = 0.34, p&amp;lt;0.001), and an equally weak negative correlation with CD8+TNF+ (Spearman\u2019s rho = -0.23, p&amp;lt;0.01). Other variables, such as gender and job category, did not significantly impact the vaccine-induced, anti-spike T cell immune response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>No distinct relationship between CD4+ and CD8+ T cell subsets was observed post-vaccination. However, specific dynamic changes in vaccine-induced T cells were identified showing clear dose- and time-dependence. Finally, the median level of CD8+CD154+ lymphocytes, indicative of activated T cells, was significantly associated with infection incidence and may represent a reliable predictive biomarker. This study provides evidence that the vaccine-induced anti-spike cellular immune response should be considered when making vaccination decisions, as it has predictive value for infection risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1707449","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T06:25:21Z","timestamp":1764051921000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["A comprehensive longitudinal analysis of the cellular immune response specific to the spike protein in healthcare workers vaccinated against SARS-CoV-2\u2013 ORCHESTRA 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