BCG Vaccination Potentially Modulates the Transcriptome of Infant CD4 T Cells in Addition to Age-Dependent Immune Ontogeny-Associated Changes

TL;DR

This study shows that the BCG vaccine affects the gene activity in infant CD4 T cells, possibly improving their immune response to infections.

Contribution

The study reveals that BCG vaccination modulates the transcriptome of infant CD4 T cells, linking it to immune function changes.

Findings

Infant CD4 T cells show a shift toward Th1 and Th17 immunity in the first three months of life.

BCG vaccination induces additional transcriptome changes in CD4 T cells related to metabolomic functions.

The findings align with BCG effects observed in adults, suggesting similar immune modulation in infants.

Abstract

Background: The Bacille Calmette–Guérin (BCG) vaccine is part of the Extended Programme on Immunization (EPI) and as such is generally administered at birth. The global introduction of BCG not only protected many vaccinated infants against severe complications of tuberculosis but also resulted in markedly reduced overall childhood mortality. Studies in human adults determined that BCG vaccination induces epigenetic reprogramming of innate immune cells (also known as trained immunity) and can also enhance T cell responses to both mycobacterial and non-mycobacterial antigens. Goal and Methods: The current study tested the hypothesis that BCG immunization similarly impacts the functionally distinct infant immune system. Towards this goal, we applied RNA sequencing to assess transcriptome changes in circulating CD4+ T cells of Malawian infants prior to and 2 to 13 weeks after BCG immunization. Results: In the first three months of life, transcriptome changes of infant CD4 T cells implied a functional shift towards T helper 1 and Th17 immunity. Vaccination with BCG resulted in additional modulation of the CD4 T cell transcriptome and differentially expressed genes could be linked to metabolomic function. Conclusions: These findings are consistent with data reported in BCG vaccinated adults and contribute to the understanding of molecular changes in infant CD4 T cells that may explain the improved capacity of the infant immune system to respond to pathogens after BCG vaccination.

Figures