# Downregulated Expression of the IL7R and BACH2 Genes Is Associated with Immune Memory Loss in Adults Vaccinated Against HBV at Birth

## TL;DR

This study finds that lower expression of IL7R and BACH2 genes in T cells is linked to loss of immune memory in adults vaccinated against hepatitis B at birth.

## Contribution

The study identifies IL7R and BACH2 as candidate genes associated with immune memory loss after early-life vaccination.

## Key findings

- IL7R expression in total T cells is significantly downregulated in individuals with immune memory loss.
- BACH2 expression in naive CD4+ and CD8+ T cells is also significantly reduced in these individuals.
- Downregulation of these genes is associated with the loss of immune memory following early-life HBV vaccination.

## Abstract

Immunization is the most effective way to prevent transmission of the hepatitis B virus. However, about one-quarter of hepatitis B vaccinees (HepB vaccinees) aged around 18 years have lost their immune memory. What is responsible for the loss? Five subjects who became asymptomatic HBsAg carriers after anti-HBs seroconversion and ten controls who were negative for both HBsAg and anti-HBs were recruited from individuals born in 1987 and vaccinated at birth. scRNA-seq was performed on peripheral blood mononuclear cells, including library preparation, sequencing, quality control and filtering, normalization, dimensionality reduction, clustering, cell type annotation, differential expression analysis and trajectory analysis. Twelve cell types and nine subpopulations of T cells were identified. No significant differences in the proportions of cell types and subpopulations were found between cases and controls. The expression levels of immune memory-related genes, IL7R in total T cells and BACH2 in naive CD4+ T cells and naive CD8+ T cells, were significantly downregulated in the cases (p = 2.2 × 10−308, 3.31 × 10−27 and 9.41 × 10−100, respectively). IL7R is expressed throughout cellular development, while BACH2 is expressed only in the early stage of cellular development. Downregulation of the IL7R and BACH2 in T cells is associated with immune memory loss, identifying them as candidate genes for future functional studies to explore their potential role in the loss of immune memory. This could inform adjuvant design if a causal mechanism is firmly established.