MMR vaccination induces a trained immunity program characterized by functional and metabolic reprogramming of γδ T cells

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. By using single-cell RNA-sequencing, we found that MMR caused transcriptomic changes in CD14-positive monocytes and NK cells, but most profoundly in γδ T cells. Surprisingly, monocyte function was not altered by MMR vaccination. In contrast, the function of γδ T cells was significantly enhanced by MMR vaccination, with higher production of TNF and IFNγ, as well as upregulation of cellular metabolic pathways. In conclusion, we describe a new trained immunity program characterized by modulation of γδ T cell function induced by MMR vaccination. ### Competing Interest Statement MGN is a scientific founder and member of the scientific advisory board of Trained Therapeutix Discovery.