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

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     «

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, Ga...     »

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.      «

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, augmenti...     »