Inflammatory mediators of mRNA vaccine-induced adverse reactions in mice

Area of Science:

• Immunology
• Vaccinology
• Pharmacology

Background:

• Messenger RNA (mRNA) vaccines are crucial for infectious disease control.
• Adverse reactions, including fever and fatigue, can occur post-vaccination, potentially increasing with booster doses and leading to vaccine hesitancy.

Purpose of the Study:

• To elucidate the mechanisms behind systemic and local adverse reactions following primary and booster mRNA vaccinations in a mouse model.
• To identify the specific components and molecular mediators responsible for these reactions.

Main Methods:

• Mice were administered prime and boost mRNA vaccinations.
• Systemic and local adverse reactions were monitored.
• Key cytokines (e.g., IL-1, IL-6, TNF-α, type 1 IFN) and inflammatory mediators (COX-2, PGE2) were analyzed.
• The impact of IL-6 inhibition on adverse reactions and vaccine effects was assessed.

Main Results:

• mRNA vaccination induced systemic adverse reactions (fever) and local reactions (increased vascular permeability).
• Lipid nanoparticles (LNPs) were identified as a major contributor to these adverse reactions.
• Systemic reactions involved IL-1, IL-6, TNF-α, type 1 IFN, COX-2, and PGE2.
• Boost vaccination enhanced TNF-α levels via IFN-γ from T cells, exacerbating systemic reactions.
• Local reactions stemmed from distinct mechanisms.
• Inhibiting IL-6 effectively reduced adverse reactions without compromising vaccine effects.

Conclusions:

• Lipid nanoparticles (LNPs) are key drivers of mRNA vaccine-induced adverse reactions.
• Understanding the cytokine and inflammatory mediator pathways involved is crucial for mitigating side effects.
• Targeting IL-6 presents a promising strategy to reduce adverse reactions while maintaining mRNA vaccine efficacy.