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Integrative Epigenomic and Transcriptomic Analysis of Peripheral Blood Across Different SARS-CoV-2 Vaccine Recipients Reveals TGF-β-Mediated Exhaustion Mechanisms

GSE318176 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 38 samples Submitted 2026/02/02 Platform GPL24676
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 38 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Homo sapiens (human)
Samples
38 samples: 8 conditions, mostly with about 6 replicates eachGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
While distinct SARS-CoV-2 vaccine platforms have demonstrated variable clinical efficacy, the molecular and epigenetic mechanisms driving these immunological disparities remain incompletely understood. Here, we present a high-resolution single-cell multi-omics atlas profiling the transcriptomic and epigenomic landscapes of peripheral immune cells across mRNA, viral vector, and protein subunit vaccine recipients.
Read the full summary ↓
Our integrative analysis reveals that viral vector and protein subunit vaccines preferentially expand atypical B cell (atBC) subsets characterized by "exhausted" epigenetic signatures and regulatory potential. We identify these cells as a primary source of TGF-β, establishing a systemic negative feedback loop that acts as a homeostatic "brake" on immune activation. Mechanistically, this regulatory axis profoundly impacts the T cell compartment, particularly in protein subunit vaccine recipients. In this group, adjuvant-mediated innate priming drives robust MAIT cell activation, which is paradoxically counterbalanced by the downregulation of the TGF-β decoy receptor TGFBR3 and upregulation of signaling receptors—rendering these cells more sensitive to suppression. Consequently, unlike mRNA vaccines that appear to bypass this extensive feedback to sustain maximal immunogenicity, viral vector and protein subunit platforms induce a self-regulated immune response via the TGF-β axis. These findings highlight a fundamental trade-off between robust immunogenicity and homeostatic control, offering a novel cellular rationale for the differential waning kinetics and protection durability observed across vaccine platforms.
This dataset
Open GSE318176 in finder → Find more human RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE318176_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1416848 and SRA study SRP672086. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
8 conditions, mostly with about 6 replicates each
scRNA, PBMC, mRNA vaccinated ×6 scATAC, PBMC, mRNA vaccinated ×6 scRNA, PBMC, cross (viral vector + mRNA) vacc… ×6 scATAC, PBMC, cross (viral vector + mRNA) vac… ×6 scRNA, PBMC, protein vaccinated ×3 scATAC, PBMC, protein vaccinated ×3 scRNA, PBMC, Healthy Control ×3 scATAC, PBMC, Healthy Control ×3 +2 more

Supports a between-group comparison across 36 samples.

How we read this: 8 replicated groups read from 38 sample titles; they account for 36 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
Datasets on a similar topic

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