The Hierarchy of Healing: How mRNA Vaccines Shape T-Cell Fate

If you work on therapeutic cancer vaccines or Tcell biology, read this new preprint (Oct 27, 2025) on how RNA vaccination shapes CD8⁺ T-cell hierarchies!
What’s new in this landmark BioNTech SE × Genentech collaboration:
Using a multi-antigen mRNA vaccine, the authors show that immunodominant CD8⁺ T-cell responses cross-compete with subdominant clones via peptide–HLA-I stability, skewing dominant cells toward terminally differentiated cytotoxic phenotypes while subdominant cells adopt memory/stem-like features. Removing dominant epitopes unleashes subdominant expansion and effector differentiation—pointing to practical levers to fine-tune breadth and fate in therapeutic vaccination.

Link to the reference: Cross-competition shapes CD8+ T cell hierarchies and differentiation after RNA vaccinationv1

Why this matters for Alithea Bio:
At Alithea, our HLA immunopeptidomics profiling maps naturally presented peptides across HLA alleles and tissues. These data help anticipate epitope dominance and pMHC stability, guiding smarter antigen selection and dosing to broaden CD8⁺ responses without sacrificing potency—exactly the kind of knob this study highlights for next-gen RNA vaccines.
Immunodominance CD8Tcells mRNA CancerVaccines HLA #Immunopeptidomics BioNTech #Genentech AlitheaBio