Multi-omics integration reveals vaccine-specific molecular signatures and temporal dynamics of COVID-19 immune responses
6 affiliations
- 1Australian eHealth Research Centre, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Herston , ,
- 2Environment, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Ecosciences Precinct, Dutton Park , ,
- 3Environment, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Black Mountain, Clunies Ross Street, Acton , ,
- 4Australian Centre for Disease Preparedness (ACDP), Commonwealth Scientific and Industrial Research Organisation (CSIRO) , , ,
- 5Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne , ,
- 6Edith Cowan University, School of Medical and Health Sciences, Joondalup , ,
Abstract
Vaccination elicits systemic immune responses that extend beyond antibody and lymphocyte activation, engaging coordinated metabolic and lipid pathways that modulate immune function. Nevertheless, how systemic molecular responses differ across COVID-19 vaccine platforms, including closely related mRNA platforms, remains poorly understood. Here, we performed integrated plasma proteomic, lipidomic, and metabolomic profiling of 53 SARS-CoV-2–naïve adults vaccinated with Pfizer-BioNTech, Moderna, or AstraZeneca COVID-19 vaccines. Samples were analysed across multiple timepoints using differential analysis and DIABLO-based multi-omics integration. Our findings reveal distinct platform-associated multi-omic molecular signatures not captured by unsupervised analyses alone. Pfizer-BioNTech vaccination was associated with widespread increases in immunoglobulin and complement associated proteins, together with broad decreases in lipid abundance and bidirectional metabolite changes. In contrast, the Moderna vaccination was associated with predominantly increased lipid abundance and bidirectional metabolite changes, with minimal univariate proteomic changes. AstraZeneca induced subtler yet coherent cross-omic shifts, detectable only through integrative modelling approaches. Despite these platform-associated differences, Pfizer and Moderna shared concordant changes in a subset of metabolites, including amino-acid and TCA-cycle-associated features, within divergent lipidomic contexts. These findings demonstrate that even closely related mRNA vaccine platforms are associated with distinct systemic molecular response patterns. This study establishes integration of multi-omics (as opposed to separate single-omic analyses) as a powerful framework for characterising vaccine-associated molecular responses, identifying candidate platform-specific molecular markers, and providing candidates for future molecular stratification studies.
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BibTeX
@article{klein2026multiomics,
title = {{Multi-omics integration reveals vaccine-specific molecular signatures and temporal dynamics of COVID-19 immune responses}},
author = {Anne H. Klein and David J. Beale and Thao V. Nguyen and Jian-Wei Liu and Petrus Jansen van Vuren and Nagendrakumar B. Singanallur and Carol Lee and Andrew C. Boomer and Jennifer A. Juno and Stephen J. Kent and Adam K. Wheatley and Gough G. Au and Seshadri S. Vasan and Laurence Wilson and Alexander J. McAuley},
journal = {Frontiers in immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1815543},
url = {https://europepmc.org/article/PMC/PMC13672565},
note = {CC BY},
}
RIS
TY - JOUR
TI - Multi-omics integration reveals vaccine-specific molecular signatures and temporal dynamics of COVID-19 immune responses
AU - Anne H. Klein
AU - David J. Beale
AU - Thao V. Nguyen
AU - Jian-Wei Liu
AU - Petrus Jansen van Vuren
AU - Nagendrakumar B. Singanallur
AU - Carol Lee
AU - Andrew C. Boomer
AU - Jennifer A. Juno
AU - Stephen J. Kent
AU - Adam K. Wheatley
AU - Gough G. Au
AU - Seshadri S. Vasan
AU - Laurence Wilson
AU - Alexander J. McAuley
PY - 2026
DA - 2026/10/02
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1815543
UR - https://europepmc.org/article/PMC/PMC13672565
AB - Vaccination elicits systemic immune responses that extend beyond antibody and lymphocyte activation, engaging coordinated metabolic and lipid pathways that modulate immune function. Nevertheless, how systemic molecular responses differ across COVID-19 vaccine platforms, including closely related mRNA platforms, remains poorly understood. Here, we performed integrated plasma proteomic, lipidomic, and metabolomic profiling of 53 SARS-CoV-2–naïve adults vaccinated with Pfizer-BioNTech, Moderna, or AstraZeneca COVID-19 vaccines. Samples were analysed across multiple timepoints using differential analysis and DIABLO-based multi-omics integration. Our findings reveal distinct platform-associated multi-omic molecular signatures not captured by unsupervised analyses alone. Pfizer-BioNTech vaccination was associated with widespread increases in immunoglobulin and complement associated proteins, together with broad decreases in lipid abundance and bidirectional metabolite changes. In contrast, the Moderna vaccination was associated with predominantly increased lipid abundance and bidirectional metabolite changes, with minimal univariate proteomic changes. AstraZeneca induced subtler yet coherent cross-omic shifts, detectable only through integrative modelling approaches. Despite these platform-associated differences, Pfizer and Moderna shared concordant changes in a subset of metabolites, including amino-acid and TCA-cycle-associated features, within divergent lipidomic contexts. These findings demonstrate that even closely related mRNA vaccine platforms are associated with distinct systemic molecular response patterns. This study establishes integration of multi-omics (as opposed to separate single-omic analyses) as a powerful framework for characterising vaccine-associated molecular responses, identifying candidate platform-specific molecular markers, and providing candidates for future molecular stratification studies.
SN - 1664-3224
ER -