MMR vaccination induces trained immunity via functional and metabolic reprogramming of [gamma][delta] 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. Using single-cell RNA-Seq, we found that MMR caused transcriptomic changes in [CD14.sup.+] 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.
Introduction Vaccines are developed to target specific pathogens. However, an accumulating body of evidence suggests that certain live-attenuated vaccines provide a broad spectrum of protection against heterologous infections as well [...]