Young infants display heterogeneous serological responses and extensive but reversible transcriptional changes following initial immunizations
Nima Nouri, Raquel Giacomelli Cao, Eleonora Bunsow, Djamel Nehar-Belaid, Radu Marcheş, Zhaohui Xu, B. Smith, Santtu Heinonen, Sara Mertz, Amy L. Leber, Gaby Smits, Fiona van der Klis, Asunción Mejías, Jacques Banchereau, Virginia Pascual, Octavio Ramilo
Abstract
Abstract 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 ISG hi 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+ ISG hi 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.