MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines
2
Issued Date
2025-08-29
Resource Type
eISSN
24709468
Scopus ID
2-s2.0-105015011392
Pubmed ID
40880519
Journal Title
Science Immunology
Volume
10
Issue
110
Rights Holder(s)
SCOPUS
Bibliographic Citation
Science Immunology Vol.10 No.110 (2025) , eadu3337
Suggested Citation
Amini A., Garner L.C., Shaw R.H., Kelly N.W., Adele S., Skelly D.T., Dejnirattisai W., Greenland M., Liu X., Heslington A., Hackstein C.P., Murray S.M., Vano C.R., Stafford L., Johnson S., Sayaf K., Pudjohartono M.F., Clutterbuck E.A., Bibi S., Conlon C.P., James T., Jeffery K., Kronsteiner B., Mentzer A.J., O'Shea D., Ramasamy M.N., Screaton G.R., Snape M.D., Hogan A.E., Barnes E., Lambe T., Dunachie S.J., Provine N.M., Klenerman P. MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines. Science Immunology Vol.10 No.110 (2025) , eadu3337. doi:10.1126/sciimmunol.adu3337 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/112070
Title
MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines
Author(s)
Amini A.
Garner L.C.
Shaw R.H.
Kelly N.W.
Adele S.
Skelly D.T.
Dejnirattisai W.
Greenland M.
Liu X.
Heslington A.
Hackstein C.P.
Murray S.M.
Vano C.R.
Stafford L.
Johnson S.
Sayaf K.
Pudjohartono M.F.
Clutterbuck E.A.
Bibi S.
Conlon C.P.
James T.
Jeffery K.
Kronsteiner B.
Mentzer A.J.
O'Shea D.
Ramasamy M.N.
Screaton G.R.
Snape M.D.
Hogan A.E.
Barnes E.
Lambe T.
Dunachie S.J.
Provine N.M.
Klenerman P.
Garner L.C.
Shaw R.H.
Kelly N.W.
Adele S.
Skelly D.T.
Dejnirattisai W.
Greenland M.
Liu X.
Heslington A.
Hackstein C.P.
Murray S.M.
Vano C.R.
Stafford L.
Johnson S.
Sayaf K.
Pudjohartono M.F.
Clutterbuck E.A.
Bibi S.
Conlon C.P.
James T.
Jeffery K.
Kronsteiner B.
Mentzer A.J.
O'Shea D.
Ramasamy M.N.
Screaton G.R.
Snape M.D.
Hogan A.E.
Barnes E.
Lambe T.
Dunachie S.J.
Provine N.M.
Klenerman P.
Author's Affiliation
University of Oxford
Technische Universität München
University of Oxford Medical Sciences Division
Nuffield Department of Medicine
Siriraj Hospital
Oxford University Hospitals NHS Foundation Trust
Maynooth University
St Vincent's University Hospital
NIHR Oxford Biomedical Research Centre
Mahidol Oxford Tropical Medicine Research Unit
Children’s Health Ireland
Technische Universität München
University of Oxford Medical Sciences Division
Nuffield Department of Medicine
Siriraj Hospital
Oxford University Hospitals NHS Foundation Trust
Maynooth University
St Vincent's University Hospital
NIHR Oxford Biomedical Research Centre
Mahidol Oxford Tropical Medicine Research Unit
Children’s Health Ireland
Corresponding Author(s)
Other Contributor(s)
Abstract
Adenoviral (Ad) vectors and mRNA vaccines exhibit distinct patterns of immune responses and reactogenicity, but underpinning mechanisms remain unclear. We longitudinally compared homologous ChAdOx1 nCoV-19 and BNT162b2 vaccination, focusing on cytokine-responsive innate-like lymphocytes-mucosal-associated invariant T (MAIT) cells and Vδ2+ γδ T cells-which sense and tune innate-adaptive cross-talk. Ad priming elicited robust type I interferon (IFN)-mediated innate-like T cell activation, augmenting T cell responses (innate-to-adaptive signaling), which was dampened at boost by antivector immunity. Conversely, mRNA boosting enhanced innate-like responses, driven by prime-induced spike-specific memory T cell-derived IFN-γ (adaptive-to-innate signaling). Extending the dosing interval dampened inflammation at boost because of waning T cell memory. In a separate vaccine trial, preboost spike-specific T cells predicted severe mRNA reactogenicity regardless of the priming platform or interval. Overall, bidirectional innate-like and adaptive cross-talk, and IFN-γ-licensed innate-like T cells, orchestrate interval-dependent early vaccine responses, suggesting modifiable targets for safer, more effective regimens.