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

Trained immunity, a de-facto innate immune memory, has been extensively studied in response to live-attenuated vaccines, but its presence following the new COVID-19 vaccines has not yet been fully elucidated. In this study, we investigate markers of trained immunity in individuals vaccinated with mRNA-1273 or BNT162b2. As part of the vaccine roll-out in Denmark and recruited for a comparative study. Our primary objective was to determine whether these vaccines elicit lasting changes in innate immune responses, particularly in monocyte populations and cytokine production following stimulation with a panel of agonists. The study was conducted at four time points: Day-0 (pre-vaccination), Day-28, Day-90, and Day-180 post-vaccination. We observed no significant differences in monocyte subpopulations between vaccine groups; however, cytokine and chemokine analysis revealed distinct immune signatures. While IL-6 and TNFα production remained unchanged after ex-vivo restimulation in the BNT162b2 group, individuals vaccinated with mRNA-1273 exhibited a sustained increase in the production of these cytokines, persisting for up to 180 days post-vaccination. Additionally, CCL2, a key chemokine involved in monocyte recruitment, was upregulated following mRNA-1273 vaccination but decreased in the BNT162b2 group, further supporting the finding of differential innate immune responses between the two vaccines. In conclusion, our study provides evidence that mRNA-1273, but not BNT162b2, induces immune responses consistent with the concept of trained immunity. These results highlight the potential for mRNA vaccine platforms to shape innate immunity, with implications for future vaccine design aimed at enhancing non-specific and specific protection against infectious diseases.