Young infants display heterogeneous serological responses and extensive but reversible transcriptional changes following initial immunizations. Young infants display heterogeneous serological responses and extensive but reversible transcriptional changes following initial immunizations

Infants necessitate vaccinations to prevent life-threatening infections. Our understanding of the infant immune responses to routine vaccines remains limited. We analyzed two cohorts of 2-month-old infants before vaccination, one week, and one-month post-vaccination. We report remarkable heterogeneity but limited antibody responses to the different antigens. Whole-blood transcriptome analysis in an initial cohort showed marked overexpression of interferon-stimulated genes (ISGs) and to a lesser extent of inflammation-genes at day 7, which normalized one month post-vaccination. Single-cell RNA sequencing in peripheral blood mononuclear cells from a second cohort identified at baseline a predominantly naive immune landscape including ISGhi cells. On day 7, increased expression of interferon-, inflammation-, and cytotoxicity-related genes were observed in most immune cells, that reverted one month post-vaccination, when a CD8+ ISGhi and cytotoxic cluster and B cells expanded. Antibody responses were associated with baseline frequencies of plasma cells, B-cells, and monocytes, and induction of ISGs at day 7. Overall design: Here, we report on a longitudinal (time-series experiments), systems-level analysis of infants' responses to initial immunizations. We investigated the effects of the 2-month routine vaccination on the PBMCs transcriptome. ***RNA-Seq raw data is to be made available through dbGaP (controlled access; phs002926)***