2025/06/10 by László Dézsi, Gábor Kökény, Gábor Szénási +15
Medicine · Immunology and Microbiology · Agricultural and Biological Sciences · #Food Allergy and Anaphylaxis Research #Immune Response and Inflammation #Animal Virus Infections Studies
paper · doi:10.1111/bph.70563
BACKGROUND AND PURPOSE: Rare but severe adverse events (AEs) associated with mRNA-lipid nanoparticle (LNP) COVID-19 vaccines, such as Comirnaty, include anaphylaxis and inflammatory organ disorders, but their underlying mechanisms are poorly understood. We aimed to develop an animal model to study these phenomena. EXPERIMENTAL APPROACH: Naive and anti-polyethylene (PEG) antibody-sensitised pigs were injected with Comirnaty i.v. Responses were evaluated by haemodynamic monitoring, haematological changes and analysis of inflammatory markers. Inflammatory cytokine gene up-regulation was tested by RT-qPCR at 6 h and at 2 and 6 weeks after vaccination. Vaccine mRNA uptake was followed, and histopathology and spike protein immunohistochemistry were performed in selected organs. KEY RESULTS: Cardiopulmonary distress of varying severity developed within minutes after each Comirnaty injection. Vaccine mRNA accumulation peaked in peripheral mononuclear cells (PBMC) within 15 min and then began to decline within minutes. After 6 h vaccine mRNA was high in liver and spleen, moderate in kidney, lymph nodes, and heart, and low in brain. At the same time expression of mRNA for proinflammatory cytokines (IL-1RA, CXCL10, TNF-α, CCL2) varied in different organs and paralleled with vaccine mRNA uptake, suggesting a close association. Histological abnormalities and spike protein immunopositivity were noted in kidney, heart and brain. CONCLUSIONS AND IMPLICATIONS: This porcine model revealed systemic anaphylactic reactivity and multiorgan vaccine mRNA uptake following i.v. injection of mRNA-LNPs, with organ-specific inflammatory response at 6 h and thereafter. These findings provide mechanistic insights into rare vaccine-related acute AEs and suggest future efforts to improve the safety of the mRNA-LNP platform.