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Dosing interval is a major factor determining the quality of T cells induced by SARS-CoV-2 mRNA and adenoviral vector vaccines

Abstract:
Functional T cell responses are crucial for protective immunity induced by COVID-19 vaccination, but factors influencing the quality of these responses are incompletely understood. We used an activation-induced marker (AIM) assay and single-cell transcriptomic sequencing to analyze SARS-CoV-2 spike-responsive T cells after mild SARS-CoV-2 infection or after one or two doses of mRNA-lipid nanoparticle (mRNA-LNP) or adenoviral-vectored COVID-19 vaccines. Our findings revealed broad functional and clonal heterogeneity in T cells generated by vaccination or infection, including multiple distinct effector populations. T cell function was largely conserved between COVID-19 vaccine platforms but was distinct compared with SARS-CoV-2 infection. Notably, the dosing interval greatly influenced the quality of T cells after two vaccine doses, particularly after mRNA-LNP vaccination, where a longer interval led to reduced inflammatory signaling and increased secondary proliferation. These insights enhance our understanding of SARS-CoV-2-specific T cells and inform the optimization of mRNA vaccination regimens.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1126/sciimmunol.adu4610

Authors

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Institution:
University of Oxford
Division:
MSD
Department:
NDM
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
NDM Experimental Medicine
Oxford college:
St John's College
Role:
Author
ORCID:
0000-0002-6837-8881
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Pandemic Sciences Institute
Oxford college:
Merton College
Role:
Author
ORCID:
0000-0002-6461-252X
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Pandemic Sciences Institute
Role:
Author


More from this funder
Funder identifier:
https://ror.org/03x94j517
Grant:
MR/Y004450/1
More from this funder
Funder identifier:
https://ror.org/0439y7842
Grant:
EP/R013756/1
More from this funder
Funder identifier:
https://ror.org/029chgv08
Grant:
227217/Z/23/Z
222426/Z/21/Z
220991/Z/20/Z
216417/Z/19/Z
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Funder identifier:
https://ror.org/001aqnf71
Grant:
MR/W02067X/1
MC_PC_19055
More from this funder
Funder identifier:
https://ror.org/0187kwz08
Grant:
COVID-19-RECPLAS
NIHR300791


Publisher:
American Association for the Advancement of Science
Journal:
Science Immunology More from this journal
Volume:
10
Issue:
110
Article number:
eadu4610
Publication date:
2025-08-29
Acceptance date:
2025-08-07
DOI:
EISSN:
2470-9468
Pmid:
40880518

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