Mass cytometry of early immune remodeling after mRNA booster vaccination reveals exploratory CD4 naive T-cell associations with documented breakthrough infection
- 1Bio-X Center for Interdisciplinary Innovation, Yunnan University , , ,
Abstract
Background
Messenger RNA (mRNA) vaccines rapidly engage innate and adaptive immunity, but the systemic immune changes occurring within 24 h of vaccination remain incompletely understood. We investigated whether early cellular and global H3K27ac/m6A changes were associated with subsequent documented breakthrough infection (BTI).Methods
We performed an exploratory longitudinal systems-immunology analysis of an outcome-balanced subset of 124 participants from a randomized trial of COVID-19 mRNA booster vaccination (62 BTI and 62 non-BTI). Peripheral blood mononuclear cells collected at Day 0 and Day 1 were profiled by high-dimensional mass cytometry. Seventeen major immune-cell populations were assessed for changes in relative abundance, marker profiles, and global H3K27ac/m6A signals. Neutralizing-antibody responses were measured through Day 180.Results
Within 24 h, booster vaccination induced rapid lineage-specific remodeling of circulating immune composition. Classical and intermediate monocytes showed positive shifts in CLR-transformed relative abundance, whereas pDCs, NK cells, and selected CD8 and unconventional T-cell populations showed negative shifts. CD4 T-cell populations remained comparatively stable on this relative-composition scale. Early H3K27ac and m6A changes correlated with abundance changes in selected innate and T-cell populations. Associations with later humoral immunity were limited: after exclusion of antibody measurements obtained on or after documented BTI, no association between early H3K27ac/m6A changes and Day 14 or Day 180 neutralizing-antibody responses remained significant after multiple-testing correction. Major-cell abundance trajectories did not differ significantly by subsequent BTI status. In contrast, BTI was associated with smaller Day 0-to-Day 1 changes in CD4_Tn IFN-Th1 chemokine, cytotoxic-Th1-associated, and CCL2-CCR2-associated marker scores and in the m6A readout.Conclusions
mRNA booster vaccination induces rapid, cell-type-specific immune remodeling within 24 h. Major-cell abundance changes were broadly shared across BTI groups, whereas early CD4_Tn marker-associated and m6A signal changes were associated with subsequent documented BTI. These findings support further evaluation of dynamic early immune states as correlates of heterogeneity in vaccine responses.
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BibTeX
@article{yu2026mass,
title = {{Mass cytometry of early immune remodeling after mRNA booster vaccination reveals exploratory CD4 naive T-cell associations with documented breakthrough infection}},
author = {Xuanjing Yu and Xinyu Jiang and Yupeng Xue and Yuqi Ji and Chunmei Li and Zijie Scott Zhang and Rui Cheng},
journal = {Frontiers in cellular and infection microbiology},
year = {2026},
month = oct,
doi = {10.3389/fcimb.2026.1966930},
url = {https://europepmc.org/article/PMC/PMC13716633},
note = {CC BY},
}
RIS
TY - JOUR
TI - Mass cytometry of early immune remodeling after mRNA booster vaccination reveals exploratory CD4 naive T-cell associations with documented breakthrough infection
AU - Xuanjing Yu
AU - Xinyu Jiang
AU - Yupeng Xue
AU - Yuqi Ji
AU - Chunmei Li
AU - Zijie Scott Zhang
AU - Rui Cheng
PY - 2026
DA - 2026/10/15
JO - Frontiers in cellular and infection microbiology
DO - 10.3389/fcimb.2026.1966930
UR - https://europepmc.org/article/PMC/PMC13716633
AB - Background Messenger RNA (mRNA) vaccines rapidly engage innate and adaptive immunity, but the systemic immune changes occurring within 24 h of vaccination remain incompletely understood. We investigated whether early cellular and global H3K27ac/m6A changes were associated with subsequent documented breakthrough infection (BTI).Methods We performed an exploratory longitudinal systems-immunology analysis of an outcome-balanced subset of 124 participants from a randomized trial of COVID-19 mRNA booster vaccination (62 BTI and 62 non-BTI). Peripheral blood mononuclear cells collected at Day 0 and Day 1 were profiled by high-dimensional mass cytometry. Seventeen major immune-cell populations were assessed for changes in relative abundance, marker profiles, and global H3K27ac/m6A signals. Neutralizing-antibody responses were measured through Day 180.Results Within 24 h, booster vaccination induced rapid lineage-specific remodeling of circulating immune composition. Classical and intermediate monocytes showed positive shifts in CLR-transformed relative abundance, whereas pDCs, NK cells, and selected CD8 and unconventional T-cell populations showed negative shifts. CD4 T-cell populations remained comparatively stable on this relative-composition scale. Early H3K27ac and m6A changes correlated with abundance changes in selected innate and T-cell populations. Associations with later humoral immunity were limited: after exclusion of antibody measurements obtained on or after documented BTI, no association between early H3K27ac/m6A changes and Day 14 or Day 180 neutralizing-antibody responses remained significant after multiple-testing correction. Major-cell abundance trajectories did not differ significantly by subsequent BTI status. In contrast, BTI was associated with smaller Day 0-to-Day 1 changes in CD4_Tn IFN-Th1 chemokine, cytotoxic-Th1-associated, and CCL2-CCR2-associated marker scores and in the m6A readout.Conclusions mRNA booster vaccination induces rapid, cell-type-specific immune remodeling within 24 h. Major-cell abundance changes were broadly shared across BTI groups, whereas early CD4_Tn marker-associated and m6A signal changes were associated with subsequent documented BTI. These findings support further evaluation of dynamic early immune states as correlates of heterogeneity in vaccine responses.
SN - 2235-2988
ER -