tetano
Editor, Senior Moderator
Front Immunol
. 2025 Nov 25:16:1707449.
doi: 10.3389/fimmu.2025.1707449. eCollection 2025. A comprehensive longitudinal analysis of the cellular immune response specific to the spike protein in healthcare workers vaccinated against SARS-CoV-2- ORCHESTRA Project
Stefano Ugel[SUP] 1 [/SUP], Akshita Gupta[SUP] 2 [/SUP], Gianluca Spiteri[SUP] 3 [/SUP], Pierpaolo Marchetti[SUP] 4 [/SUP], Francesco De Sanctis[SUP] 1 [/SUP], Shari Wouters[SUP] 2 [/SUP], Angelina Konnova[SUP] 2 [/SUP], Maria Grazia Lourdes Monaco[SUP] 3 5 [/SUP], Angela Carta[SUP] 3 5 [/SUP], Maria Diletta Pezzani[SUP] 6 [/SUP], Filippo Liviero[SUP] 7 8 [/SUP], Sofia Pavanello[SUP] 7 8 9 [/SUP], Marco dell'Omo[SUP] 10 [/SUP], Eleonóra Fabiánová[SUP] 11 [/SUP], Jana Bérešová[SUP] 11 [/SUP], Francesca Larese Filon[SUP] 12 [/SUP], Marcella Mauro[SUP] 12 [/SUP], Giuseppe Verlato[SUP] 4 [/SUP], Vincenzo Bronte[SUP] 1 [/SUP], Samir Kumar-Singh[SUP] 2 [/SUP], Stefano Porru[SUP] 3 5 [/SUP]
Affiliations
Introduction: 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.
Methods: 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-α, IFN-γ, IL-2), functional activation (CD154), and memory differentiation (CD45RO).
Results: 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's rho = 0.34, p<0.001), and an equally weak negative correlation with CD8+TNF+ (Spearman's rho = -0.23, p<0.01). Other variables, such as gender and job category, did not significantly impact the vaccine-induced, anti-spike T cell immune response.
Discussion: 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.
Keywords: SARS-CoV-2 infection (COVID-19); anti-spike T-cell response; cytotoxic T cells (CTLs); mRNA vaccine against SARS-CoV-2; post-vaccination immunity.
. 2025 Nov 25:16:1707449.
doi: 10.3389/fimmu.2025.1707449. eCollection 2025. A comprehensive longitudinal analysis of the cellular immune response specific to the spike protein in healthcare workers vaccinated against SARS-CoV-2- ORCHESTRA Project
Stefano Ugel[SUP] 1 [/SUP], Akshita Gupta[SUP] 2 [/SUP], Gianluca Spiteri[SUP] 3 [/SUP], Pierpaolo Marchetti[SUP] 4 [/SUP], Francesco De Sanctis[SUP] 1 [/SUP], Shari Wouters[SUP] 2 [/SUP], Angelina Konnova[SUP] 2 [/SUP], Maria Grazia Lourdes Monaco[SUP] 3 5 [/SUP], Angela Carta[SUP] 3 5 [/SUP], Maria Diletta Pezzani[SUP] 6 [/SUP], Filippo Liviero[SUP] 7 8 [/SUP], Sofia Pavanello[SUP] 7 8 9 [/SUP], Marco dell'Omo[SUP] 10 [/SUP], Eleonóra Fabiánová[SUP] 11 [/SUP], Jana Bérešová[SUP] 11 [/SUP], Francesca Larese Filon[SUP] 12 [/SUP], Marcella Mauro[SUP] 12 [/SUP], Giuseppe Verlato[SUP] 4 [/SUP], Vincenzo Bronte[SUP] 1 [/SUP], Samir Kumar-Singh[SUP] 2 [/SUP], Stefano Porru[SUP] 3 5 [/SUP]
Affiliations
- PMID: 41376637
- PMCID: PMC12685908
- DOI: 10.3389/fimmu.2025.1707449
Introduction: 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.
Methods: 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-α, IFN-γ, IL-2), functional activation (CD154), and memory differentiation (CD45RO).
Results: 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's rho = 0.34, p<0.001), and an equally weak negative correlation with CD8+TNF+ (Spearman's rho = -0.23, p<0.01). Other variables, such as gender and job category, did not significantly impact the vaccine-induced, anti-spike T cell immune response.
Discussion: 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.
Keywords: SARS-CoV-2 infection (COVID-19); anti-spike T-cell response; cytotoxic T cells (CTLs); mRNA vaccine against SARS-CoV-2; post-vaccination immunity.