Image 3_A comprehensive longitudinal analysis of the cellular immune response specific to the spike protein in healthcare workers vaccinated against SARS-CoV-2– ORCHESTRA Project.pdf
Introduction<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 work...
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2025
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| author | Stefano Ugel (7402733) |
| author2 | Akshita Gupta (9861964) Gianluca Spiteri (13881092) Pierpaolo Marchetti (3574394) Francesco De Sanctis (8497395) Shari Wouters (22679114) Angelina Konnova (14292068) Maria Grazia Lourdes Monaco (13881095) Angela Carta (384367) Maria Diletta Pezzani (22679117) Filippo Liviero (11175000) Sofia Pavanello (550275) Marco dell’Omo (8872523) Eleonóra Fabiánová (162234) Jana Bérešová (13881107) Francesca Larese Filon (11527932) Marcella Mauro (11527929) Giuseppe Verlato (412001) Vincenzo Bronte (234424) Samir Kumar-Singh (305527) Stefano Porru (384360) Orchestra WP5 and WP6 Working Groups (22679141) |
| author2_role | author author author author author author author author author author author author author author author author author author author author author |
| author_facet | Stefano Ugel (7402733) Akshita Gupta (9861964) Gianluca Spiteri (13881092) Pierpaolo Marchetti (3574394) Francesco De Sanctis (8497395) Shari Wouters (22679114) Angelina Konnova (14292068) Maria Grazia Lourdes Monaco (13881095) Angela Carta (384367) Maria Diletta Pezzani (22679117) Filippo Liviero (11175000) Sofia Pavanello (550275) Marco dell’Omo (8872523) Eleonóra Fabiánová (162234) Jana Bérešová (13881107) Francesca Larese Filon (11527932) Marcella Mauro (11527929) Giuseppe Verlato (412001) Vincenzo Bronte (234424) Samir Kumar-Singh (305527) Stefano Porru (384360) Orchestra WP5 and WP6 Working Groups (22679141) |
| author_role | author |
| dc.creator.none.fl_str_mv | Stefano Ugel (7402733) Akshita Gupta (9861964) Gianluca Spiteri (13881092) Pierpaolo Marchetti (3574394) Francesco De Sanctis (8497395) Shari Wouters (22679114) Angelina Konnova (14292068) Maria Grazia Lourdes Monaco (13881095) Angela Carta (384367) Maria Diletta Pezzani (22679117) Filippo Liviero (11175000) Sofia Pavanello (550275) Marco dell’Omo (8872523) Eleonóra Fabiánová (162234) Jana Bérešová (13881107) Francesca Larese Filon (11527932) Marcella Mauro (11527929) Giuseppe Verlato (412001) Vincenzo Bronte (234424) Samir Kumar-Singh (305527) Stefano Porru (384360) Orchestra WP5 and WP6 Working Groups (22679141) |
| dc.date.none.fl_str_mv | 2025-11-25T06:16:16Z |
| dc.identifier.none.fl_str_mv | 10.3389/fimmu.2025.1707449.s002 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/figure/Image_3_A_comprehensive_longitudinal_analysis_of_the_cellular_immune_response_specific_to_the_spike_protein_in_healthcare_workers_vaccinated_against_SARS-CoV-2_ORCHESTRA_Project_pdf/30703820 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Genetic Immunology SARS-CoV-2 infection (COVID-19) mRNA vaccine against SARS-CoV-2 post-vaccination immunity anti-spike T-cell response cytotoxic T cells (CTLs) |
| dc.title.none.fl_str_mv | Image 3_A comprehensive longitudinal analysis of the cellular immune response specific to the spike protein in healthcare workers vaccinated against SARS-CoV-2– ORCHESTRA Project.pdf |
| dc.type.none.fl_str_mv | Image Figure info:eu-repo/semantics/publishedVersion image |
| description | Introduction<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.</p>Methods<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-α, IFN-γ, IL-2), functional activation (CD154), and memory differentiation (CD45RO).</p>Results<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’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.</p>Discussion<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.</p> |
| eu_rights_str_mv | openAccess |
| id | Manara_30c4013e9d18a0b9957efd3ffd5830db |
| identifier_str_mv | 10.3389/fimmu.2025.1707449.s002 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/30703820 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Image 3_A comprehensive longitudinal analysis of the cellular immune response specific to the spike protein in healthcare workers vaccinated against SARS-CoV-2– ORCHESTRA Project.pdfStefano Ugel (7402733)Akshita Gupta (9861964)Gianluca Spiteri (13881092)Pierpaolo Marchetti (3574394)Francesco De Sanctis (8497395)Shari Wouters (22679114)Angelina Konnova (14292068)Maria Grazia Lourdes Monaco (13881095)Angela Carta (384367)Maria Diletta Pezzani (22679117)Filippo Liviero (11175000)Sofia Pavanello (550275)Marco dell’Omo (8872523)Eleonóra Fabiánová (162234)Jana Bérešová (13881107)Francesca Larese Filon (11527932)Marcella Mauro (11527929)Giuseppe Verlato (412001)Vincenzo Bronte (234424)Samir Kumar-Singh (305527)Stefano Porru (384360)Orchestra WP5 and WP6 Working Groups (22679141)Genetic ImmunologySARS-CoV-2 infection (COVID-19)mRNA vaccine against SARS-CoV-2post-vaccination immunityanti-spike T-cell responsecytotoxic T cells (CTLs)Introduction<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.</p>Methods<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-α, IFN-γ, IL-2), functional activation (CD154), and memory differentiation (CD45RO).</p>Results<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’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.</p>Discussion<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.</p>2025-11-25T06:16:16ZImageFigureinfo:eu-repo/semantics/publishedVersionimage10.3389/fimmu.2025.1707449.s002https://figshare.com/articles/figure/Image_3_A_comprehensive_longitudinal_analysis_of_the_cellular_immune_response_specific_to_the_spike_protein_in_healthcare_workers_vaccinated_against_SARS-CoV-2_ORCHESTRA_Project_pdf/30703820CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/307038202025-11-25T06:16:16Z |
| spellingShingle | Image 3_A comprehensive longitudinal analysis of the cellular immune response specific to the spike protein in healthcare workers vaccinated against SARS-CoV-2– ORCHESTRA Project.pdf Stefano Ugel (7402733) Genetic Immunology SARS-CoV-2 infection (COVID-19) mRNA vaccine against SARS-CoV-2 post-vaccination immunity anti-spike T-cell response cytotoxic T cells (CTLs) |
| status_str | publishedVersion |
| title | Image 3_A comprehensive longitudinal analysis of the cellular immune response specific to the spike protein in healthcare workers vaccinated against SARS-CoV-2– ORCHESTRA Project.pdf |
| title_full | Image 3_A comprehensive longitudinal analysis of the cellular immune response specific to the spike protein in healthcare workers vaccinated against SARS-CoV-2– ORCHESTRA Project.pdf |
| title_fullStr | Image 3_A comprehensive longitudinal analysis of the cellular immune response specific to the spike protein in healthcare workers vaccinated against SARS-CoV-2– ORCHESTRA Project.pdf |
| title_full_unstemmed | Image 3_A comprehensive longitudinal analysis of the cellular immune response specific to the spike protein in healthcare workers vaccinated against SARS-CoV-2– ORCHESTRA Project.pdf |
| title_short | Image 3_A comprehensive longitudinal analysis of the cellular immune response specific to the spike protein in healthcare workers vaccinated against SARS-CoV-2– ORCHESTRA Project.pdf |
| title_sort | Image 3_A comprehensive longitudinal analysis of the cellular immune response specific to the spike protein in healthcare workers vaccinated against SARS-CoV-2– ORCHESTRA Project.pdf |
| topic | Genetic Immunology SARS-CoV-2 infection (COVID-19) mRNA vaccine against SARS-CoV-2 post-vaccination immunity anti-spike T-cell response cytotoxic T cells (CTLs) |