MMR vaccination induces trained immunity via functional and metabolic reprogramming ofæ Tcells

The measles, mumps, and rubella (MMR) vaccine protects against all -cause mortality in children, but the immunological mechanisms mediating these effects are poorly known. We systematically investigated whether MMR can induce long-term functional changes in innate immune cells, a process termed trained immunity, that could at least partially mediate this heterologous protection. In a randomized, placebo -controlled trial, 39 healthy adults received either the MMR vaccine or a placebo. Using single -cell RNA-Seq, we found that MMR caused transcriptomic changes in CD14+ monocytes and NK cells, but most profoundly in gamma delta T cells. Monocyte function was not altered by MMR vaccination. In contrast, the function of gamma delta T cells was markedly enhanced by MMR vaccination, with higher production of TNF and IFN-gamma, as well as upregulation of cellular metabolic pathways. In conclusion, we describe a trained immunity program characterized by modulation of gamma delta T cell function induced by MMR vaccination.