Dosing interval is a major factor determining the quality of T cells induced by SARS-CoV-2 mRNA and adenoviral vector vaccines
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.
Authors
- Teresa Lambe (ORCID: https://orcid.org/0000-0001-7711-897X)
- Ali Amini (ORCID: https://orcid.org/0000-0002-6837-8881)
- Nicholas M. Provine (ORCID: https://orcid.org/0000-0002-9694-2216)
- Eleanor Barnes (ORCID: https://orcid.org/0000-0002-0860-0831)
- Paul Klenerman (ORCID: https://orcid.org/0000-0003-4307-9161)
- Sam M. Murray (ORCID: https://orcid.org/0000-0002-5990-5854)
- Lucy C. Garner (ORCID: https://orcid.org/0000-0002-6461-252X)
- Andrew J. Pollard (ORCID: https://orcid.org/0000-0001-7361-719X)
- Sagida Bibi (ORCID: https://orcid.org/0000-0002-0855-2737)
- Maria Fransiska Pudjohartono (ORCID: https://orcid.org/0000-0001-6367-5046)
- Barbara Kronsteiner (ORCID: https://orcid.org/0000-0003-0867-2867)
- Susanna Dunachie (ORCID: https://orcid.org/0000-0001-5665-6293)
- Helen Ferry (ORCID: https://orcid.org/0000-0002-0558-2690)
Institutions
- Centre for Human Genetics (GB)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- University of Oxford (GB)
- Medawar Building for Pathogen Research (GB)
- Mahidol Oxford Tropical Medicine Research Unit (TH)
- Oxford BioMedica (United Kingdom) (GB)
- Science Oxford (GB)
- Oxford University Hospitals NHS Trust (GB)
Publication Details
- Journal
- Science Immunology
- Published
- 2025-08-29
- DOI
- https://doi.org/10.1126/sciimmunol.adu4610
- Citations
- 3
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 4.19