| Title: |
MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines |
| Authors: |
Amini, Ali; Garner, Lucy C.; Shaw, Robert H.; Kelly, Neil Wrigley; Adele, Sandra; Skelly, Donal T.; Dejnirattisai, Wanwisa; Greenland, Melanie; Liu, Xinxue; Heslington, Amelia; Hackstein, Carl-Philipp; Murray, Sam M.; Vano, Cristina Riquelme; Stafford, Lizzie; Johnson, Sile; Sayaf, Katia; Pudjohartono, Maria Fransiska; Clutterbuck, Elizabeth A.; Bibi, Sagida; Conlon, Christopher P.; James, Tim; Jeffery, Katie; Kronsteiner, Barbara; Mentzer, Alexander J.; O’Shea, Donal; Ramasamy, Maheshi N.; Screaton, Gavin R.; Snape, Matthew D.; Hogan, Andrew E.; Barnes, Eleanor; Lambe, Teresa; Dunachie, Susanna J.; Provine, Nicholas M.; Klenerman, Paul; Ali, Mohammad; Bridges-Webb, Alice; Chalk, Jeremy; Deeks, Alexandra S.; Dold, Christina; Eyre, David; Frater, John; Frending, Lisa; Goulder, Philip; Jamsen, Anni; Malone, Tom; Matthews, Philippa C.; Phillips, Eloise; Rongkard, Patpong; Simmons, Beatrice; Turtle, Lance |
| Source: |
Science Immunology ; volume 10, issue 110 ; ISSN 2470-9468 |
| Publisher Information: |
American Association for the Advancement of Science (AAAS) |
| Publication Year: |
2025 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1126/sciimmunol.adu3337 |
| Availability: |
https://doi.org/10.1126/sciimmunol.adu3337; https://www.science.org/doi/pdf/10.1126/sciimmunol.adu3337 |
| Accession Number: |
edsbas.18F84E8F |
| Database: |
BASE |