MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines

Ali Amini^{1

2

3

4}, Lucy C Garner^{1

3}, Robert H Shaw^{4

5}, Neil Wrigley Kelly⁶, Sandra Adele², Donal T Skelly^{2

4

7}, Wanwisa Dejnirattisai^{8

9}, Melanie Greenland⁵, Xinxue Liu⁵, Amelia Heslington¹, Carl-Philipp Hackstein^{2

10}, Sam M Murray^{2

3}, Cristina Riquelme Vano¹, Lizzie Stafford⁴, Sile Johnson^{2

4}, Katia Sayaf^{2

3}, Maria Fransiska Pudjohartono^{1

3}, Elizabeth A Clutterbuck⁵; PITCH Consortium‡; Com-COV Study Group‡; Sagida Bibi⁵, Christopher P Conlon¹¹, Tim James⁴, Katie Jeffery^{4

12}, Barbara Kronsteiner^{2

13}, Alexander J Mentzer^{4

8}, Donal O'Shea¹⁴, Maheshi N Ramasamy^{4

5

15}, Gavin R Screaton^{8

16}, Matthew D Snape⁵, Andrew E Hogan^{13

17}, Eleanor Barnes^{1

2

4

15}, Teresa Lambe^{3

5

15}, Susanna J Dunachie^{2

4

12

15

18}, Nicholas M Provine^{1

3

8}, Paul Klenerman^{1

2

3

4

15}; PITCH Consortium; Com-COV Study Group

Collaborators, Affiliations

Collaborators

PITCH Consortium:
Mohammad Ali, Alice Bridges-Webb, Jeremy Chalk, Alexandra S Deeks, Christina Dold, David Eyre, John Frater, Lisa Frending, Philip Goulder, Anni Jamsen, Tom Malone, Philippa C Matthews, Eloise Phillips, Patpong Rongkard, Beatrice Simmons, Lance Turtle
Com-COV Study Group:
Arabella S V Stuart, Parvinder K Aley, Nick J Andrews, J Claire Cameron, Sue Charlton, Andrea Collins, Tanya Dinesh, Anna England, Saul N Faust, Daniela Ferreira, Adam Finn, Christopher A Green, Bassam Hallis, Paul Heath, Helen Hill, Rajeka Lazarus, Vincenzo Libri, Yama Mujadidi, Emma Plesteda, Mary Ramsay, Robert C Read, Hannah Robinson, Nisha Singh, David P J Turner, Paul J Turner, Rachel White, Jonathan S Nguyen-Van-Tam

Affiliations

¹ Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine - Experimental Medicine, University of Oxford, Oxford, UK.
² Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
³ Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁴ Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
⁵ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
⁶ St Vincent's University Hospital and University College Dublin, Dublin, Ireland.
⁷ Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
⁸ Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁹ Division of Emerging Infectious Disease, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok Noi, Bangkok 10700, Thailand.
¹⁰ Center for Infection Prevention, Technical University of Munich, Munich, Germany.
¹¹ Nuffield Department of Medicine, University of Oxford, Oxford, UK.
¹² Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
¹³ NDM Centre for Global Health Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
¹⁴ Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Ireland.
¹⁵ NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
¹⁶ Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
¹⁷ National Children's Research Centre, Dublin, Ireland.
¹⁸ Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.

PMID: 40880519
DOI: 10.1126/sciimmunol.adu3337

MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines

Ali Amini et al. Sci Immunol. 2025.

. 2025 Aug 29;10(110):eadu3337.

doi: 10.1126/sciimmunol.adu3337. Epub 2025 Aug 29.

Authors

Collaborators

PITCH Consortium:
Mohammad Ali, Alice Bridges-Webb, Jeremy Chalk, Alexandra S Deeks, Christina Dold, David Eyre, John Frater, Lisa Frending, Philip Goulder, Anni Jamsen, Tom Malone, Philippa C Matthews, Eloise Phillips, Patpong Rongkard, Beatrice Simmons, Lance Turtle
Com-COV Study Group:
Arabella S V Stuart, Parvinder K Aley, Nick J Andrews, J Claire Cameron, Sue Charlton, Andrea Collins, Tanya Dinesh, Anna England, Saul N Faust, Daniela Ferreira, Adam Finn, Christopher A Green, Bassam Hallis, Paul Heath, Helen Hill, Rajeka Lazarus, Vincenzo Libri, Yama Mujadidi, Emma Plesteda, Mary Ramsay, Robert C Read, Hannah Robinson, Nisha Singh, David P J Turner, Paul J Turner, Rachel White, Jonathan S Nguyen-Van-Tam

Affiliations

¹ Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine - Experimental Medicine, University of Oxford, Oxford, UK.
² Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
³ Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁴ Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
⁵ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
⁶ St Vincent's University Hospital and University College Dublin, Dublin, Ireland.
⁷ Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
⁸ Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁹ Division of Emerging Infectious Disease, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok Noi, Bangkok 10700, Thailand.
¹⁰ Center for Infection Prevention, Technical University of Munich, Munich, Germany.
¹¹ Nuffield Department of Medicine, University of Oxford, Oxford, UK.
¹² Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
¹³ NDM Centre for Global Health Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
¹⁴ Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Ireland.
¹⁵ NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
¹⁶ Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
¹⁷ National Children's Research Centre, Dublin, Ireland.
¹⁸ Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.

PMID: 40880519
DOI: 10.1126/sciimmunol.adu3337

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.

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MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines

Collaborators

Affiliations

MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines

Authors

Collaborators

Affiliations

Abstract

MeSH terms

Substances