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Vaccinations01:51

Vaccinations

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Overview
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Signatures of Trained Immunity Following mRNA Vaccination: Differences Between mRNA-1273 and BNT162b2.

Martin Kunc1, Bradley Joseph Whitehead2, Lars Jørgen Østergaard2,3

  • 1Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. kunc@clin.au.dk.

Journal of Clinical Immunology
|December 23, 2025
PubMed
Summary

The mRNA-1273 COVID-19 vaccine, unlike BNT162b2, induces trained immunity, a form of innate immune memory, with sustained cytokine production up to 180 days post-vaccination.

Keywords:
BNT162b2Cytokine responseMonocytesTrained immunitymRNA vaccinesmRNA-1273

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Area of Science:

  • Immunology
  • Vaccinology

Background:

  • Trained immunity, or innate immune memory, is well-documented for live-attenuated vaccines.
  • Its induction by novel mRNA COVID-19 vaccines remains under investigation.

Purpose of the Study:

  • To investigate trained immunity markers in individuals vaccinated with mRNA-1273 or BNT162b2.
  • To compare lasting changes in innate immune responses, including monocyte populations and cytokine profiles.

Main Methods:

  • Comparative study of mRNA-1273 and BNT162b2 vaccine recipients.
  • Analysis of monocyte subpopulations and ex-vivo cytokine/chemokine production at four time points (pre-vaccination, Day-28, Day-90, Day-180).
  • Stimulation with a panel of immune agonists.

Main Results:

  • No significant differences in monocyte subpopulations were observed between vaccine groups.
  • mRNA-1273 vaccination led to sustained increases in IL-6 and TNFα production up to 180 days post-vaccination.
  • CCL2 chemokine was upregulated after mRNA-1273 vaccination, contrasting with a decrease after BNT162b2 vaccination.

Conclusions:

  • mRNA-1273 vaccination induces immune responses consistent with trained immunity, unlike BNT162b2.
  • These findings suggest mRNA vaccine platforms can shape innate immunity, impacting future vaccine design for broader protection.