Search

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 [...]

Vaccination-induced protection against influenza is greatly diminished and increasingly heterogeneous with age. We investigated longitudinally (up to five time points) a cohort of 234 vaccinated >65-year-old vaccinees with adjuvanted vaccine FluAd across two independent seasons. System-level analyses of multiomics datasets measuring six modalities and serological data revealed that poor responders lacked time-dependent changes in response to vaccination as observed in responders, suggestive of systemic dysregulation in poor responders. Multiomics integration revealed key molecules and their likely role in vaccination response. High prevaccination plasma interleukin-15 (IL-15) concentrations negatively associated with antibody production, further supported by experimental validation in mice revealing an IL-15-driven natural killer cell axis explaining the suppressive role in vaccine-induced antibody production as observed in poor responders. We propose a subset of long-chain fatty acids as modulators of persistent inflammation in poor responders. Our findings provide a potential link between low-grade chronic inflammation and poor vaccination response and open avenues for possible pharmacological interventions to enhance vaccine responses. [ABSTRACT FROM AUTHOR]