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Time-Resolved Multi-Omics Identify Biomarkers of Immediate Reactions to mRNA Vaccination
Ana Olivera1, Benjamin Schwarz2, Brittany Dulek3
1Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Allergy
|July 17, 2026
Summary
Systemic allergic reactions (sARs) and immunization stress-related responses (ISRs) after vaccination can be distinguished by unique immune and metabolic signatures. These reactions do not impair vaccine-induced antiviral or antibody immunity.
Area of Science:
- Immunology
- Vaccinology
- Systems Biology
Background:
- Systemic allergic reactions (sARs) post-vaccination are severe and can reduce vaccine confidence.
- Differentiating sARs from immunization stress-related responses (ISRs) is crucial for appropriate clinical management.
- Identifying biomarkers for sARs and ISRs can aid in diagnosis and treatment.
Purpose of the Study:
- To identify biomarkers that distinguish sARs from ISRs.
- To characterize the early immune and metabolic pathways involved in these reactions.
- To determine if immediate post-vaccination reactions affect subsequent vaccine-induced immunity.
Main Methods:
- A double-blind, placebo-controlled BNT162b2 re-vaccination trial was conducted in individuals with prior mRNA vaccine reactions.
- Samples were analyzed for transcriptomics, proteomics, metabolomics, blood counts, and flow cytometry 0.5-24 hours post-vaccination.
- Longitudinal anti-spike antibody levels were measured, with anti-nucleocapsid antibodies used to identify infections.
Main Results:
- Interferon and antiviral responses, along with anti-spike antibody production, were maintained across reaction groups.
- ISRs showed a distinct stress-metabolic profile, including norepinephrine and phosphoglycerate changes, and altered basophil and neutrophil activation.
- Systemic allergic reactions (sARs) exhibited opposite metabolic trends and early neutrophil CD63 upregulation.
- Longer intervals between vaccine doses correlated with lower antibody titers.
Conclusions:
- Time-resolved immune and metabolic signatures offer potential biomarkers for distinguishing ISRs from sARs.
- These findings have implications for the diagnosis, management, and adherence to vaccination protocols.
- Post-vaccination reactions, including sARs and ISRs, did not compromise vaccine-elicited antiviral or humoral immunity.
