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 Marches, Zhaohui Xu, Bennett Smith, Santtu Heinonen, Sara Mertz, Amy Leber, Gaby Smits, Fiona Klis, Asunción Mejías, Jacques Banchereau, Virginia Pascual () and Octavio Ramilo ()
Additional contact information
Nima Nouri: The Jackson Laboratory for Genomic Medicine
Raquel Giacomelli Cao: Abigail Wexner Research Institute at Nationwide Children’s Hospital
Eleonora Bunsow: Abigail Wexner Research Institute at Nationwide Children’s Hospital
Djamel Nehar-Belaid: The Jackson Laboratory for Genomic Medicine
Radu Marches: The Jackson Laboratory for Genomic Medicine
Zhaohui Xu: Abigail Wexner Research Institute at Nationwide Children’s Hospital
Bennett Smith: Abigail Wexner Research Institute at Nationwide Children’s Hospital
Santtu Heinonen: Abigail Wexner Research Institute at Nationwide Children’s Hospital
Sara Mertz: Abigail Wexner Research Institute at Nationwide Children’s Hospital
Amy Leber: Nationwide Children’s Hospital
Gaby Smits: National Institute for Public Health and the Environment (RIVM)
Fiona Klis: National Institute for Public Health and the Environment (RIVM)
Asunción Mejías: Abigail Wexner Research Institute at Nationwide Children’s Hospital
Jacques Banchereau: The Jackson Laboratory for Genomic Medicine
Virginia Pascual: Weill Cornell Medicine
Octavio Ramilo: Abigail Wexner Research Institute at Nationwide Children’s Hospital

Nature Communications, 2023, vol. 14, issue 1, 1-16

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 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.

Date: 2023
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DOI: 10.1038/s41467-023-43758-2

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