BNT162b2 vaccine not only targets COVID-19 virus, but may also help reduce and control innate inflammation

Posted on: 28 April 2025

Trinity researchers have found that the BNT162b2 COVID-19 vaccine may offer protection beyond its intended, primary target. In a study, recently published in the Clinical Immunology journal. Researchers found that the vaccine not only targeted the COVID-19 virus, it also unexpectedly helped to reduce and control innate inflammation to other bacterial and fungal pathogens not related to the vaccine target.

The innate immune system acts as our body’s first line of defence. A previously diagnosed phenomenon called trained immunity refers to the memory function within the innate immune system. It helps the body react more quickly and powerfully to a broad range of infections.

Licensed vaccines during the COVID-19 pandemic saw a shift towards using next-generation mRNA-based vaccines. The BNT162b2 mRNA vaccine proved to be highly effective against severe COVID-19 and related mortality. While SARS-CoV-2-specific-adaptive immune responses, such as antibody production and the development of classic immune memory from specialised adaptive immune cells have been well characterised, the effect of mRNA vaccination on innate immune function, up until now, has not been fully understood.

The Trinity study has discovered that the BNT162b2 COVID-19 vaccine non-specifically reduced innate immune function.

How was the research undertaken?

The Trinity research was undertaken with eight healthy volunteers who gave blood before getting the BNT162b2 mRNA COVID-19 vaccine, and again on days 14 and 28 after the first dose. Findings show that the BNT162b2 vaccine dampened the production of inflammatory mediators to bacterial, fungal and viral pathogens (compared with innate immune responses induced in the same person prior to vaccination) and proteomic analysis demonstrated a reduction in inflammatory markers post vaccination. These findings suggest that the vaccine may have broader effects on the immune system, helping to reduce inflammation in a way similar to anti-inflammatory trained immunity.

Evidence from randomised clinical control trials has powerfully demonstrated distinctions between vaccine platforms, illustrating differences in their non-specific effects, in real-world settings. Findings from the Trinity study may provide potential explanations and mechanistic insights for the observations of randomised clinical controls trials illustrating differences in non-specific effects induced by mRNA versus adenoviral vector SARS-CoV-2 vaccines.

The research suggests that the vaccine may dampen innate immune responses to secondary stimulation (bacterial, fungal or viral), thereby reducing inflammation, however underlines the importance of the context in which this reduction of  an inflammatory profile may occur. Excessive inflammation is a key feature of severe SARS-CoV-2 infection, and many other immune mediated diseases, therefore the BNT162b2 may assist in reducing and controlling innate inflammation.

Considerations for vaccine design

The study’s findings also prompt consideration for vaccine design. Despite the promise that trained immunity brings, the phenomenon has not yet become a regular part of how vaccines are designed or scheduled. Most vaccine development still focuses only on triggering the adaptive immune system. But by understanding the effect of vaccination on innate immune responses and trained immunity, we may be able to build vaccines that not only protect us from specific threats—but also help prepare our immune systems to a broad range of future infectious challenges.

Sarah Connolly, the PhD student in the Basdeo lab, St James’s Hospital who undertook this research, with funding from Research Ireland said:

“The findings of our study highlight the importance of exploring innate immune responses to vaccination after initial priming. This work establishes that mRNA vaccination can alter innate immune responses to both related and unrelated pathogens. This is impactful because it will inform on the wider immunological effects of vaccination and how this can be used to optimise vaccine design and scheduling.”

  
Dr Sharee Basdeo, principal investigator of the Human and Translational Immunology Group based in the Trinity Translational Medicine Institute at St James’s Hospital and senior author adds:

“Since the mRNA vaccine platform is new and highly successful, this study has improved our understanding of its non-specific effects on innate immunity, which will help to inform pandemic preparedness and the ability of this platform to protect against other infectious diseases or regulate inflammation.”

READ: You can read the full paper: BNT162b2 mRNA vaccination attenuates innate immune function in humans at this link: https://authors.elsevier.com/c/1ksHa5P-5qe6Aw 

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