Evidence map›Paper›PMID 41376637›Full record

ArticleFrontiers in immunology2025

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, Akshita Gupta, Gianluca Spiteri, Pierpaolo Marchetti, Francesco De Sanctis, Shari Wouters, Angelina Konnova, Maria Grazia Lourdes Monaco, Angela Carta, Maria Diletta Pezzani and 11 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Stefano UgelSection of Immunology, Department of Medicine, University of Verona, Verona, Italy.
Akshita GuptaMolecular Pathology Group, Cell Biology and Histology, Faculty of Medicine and Health Sciences and Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
Gianluca SpiteriOccupational Medicine Unit, University Hospital of Verona, Verona, Italy.
Pierpaolo MarchettiUnit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
Francesco De SanctisSection of Immunology, Department of Medicine, University of Verona, Verona, Italy.
Shari WoutersMolecular Pathology Group, Cell Biology and Histology, Faculty of Medicine and Health Sciences and Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
Angelina KonnovaMolecular Pathology Group, Cell Biology and Histology, Faculty of Medicine and Health Sciences and Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
Maria Grazia Lourdes MonacoOccupational Medicine Unit, University Hospital of Verona, Verona, Italy.
Angela CartaOccupational Medicine Unit, University Hospital of Verona, Verona, Italy.
Maria Diletta PezzaniInfectious Diseases, Department of Diagnostics and Public Health, University Hospital of Verona, Verona, Italy.
Filippo LivieroDepartment of Cardio-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy.
Sofia PavanelloDepartment of Cardio-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy.
Marco dell'OmoUnit of Occupational Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
Eleonóra FabiánováOccupational Health Department, Regional Authority of Public Health (RAPH), Banská Bystrica, Slovakia.
Jana BérešováOccupational Health Department, Regional Authority of Public Health (RAPH), Banská Bystrica, Slovakia.
Francesca Larese FilonUnit of Occupational Medicine, Department of Medical Science, University of Trieste, Trieste, Italy.
Marcella MauroUnit of Occupational Medicine, Department of Medical Science, University of Trieste, Trieste, Italy.
Giuseppe VerlatoUnit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
Vincenzo BronteSection of Immunology, Department of Medicine, University of Verona, Verona, Italy.
Samir Kumar-SinghMolecular Pathology Group, Cell Biology and Histology, Faculty of Medicine and Health Sciences and Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
Stefano PorruOccupational Medicine Unit, University Hospital of Verona, Verona, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

CD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCOVID-19COVID-19 VaccinesHealth PersonnelImmunity, CellularSARS-CoV-2Spike Glycoprotein, CoronavirusAdultCytokinesFemaleHumansLongitudinal StudiesMaleMiddle AgedVaccinationCOVID-19 VaccinesCytokinesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2anti-spike T-cell responsecytotoxic T cells (CTLs)mRNA vaccine against SARS-CoV-2post-vaccination immunitySARS-CoV-2 infection (COVID-19)

Identifiers

PMID41376637
PMCPMC12685908

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.