Acute anaphylactic and multiorgan inflammatory effects of Comirnaty in pigs

Acute anaphylactic and multiorgan inflammatory effects of Comirnaty in pigs | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 19 June 2025 V1 Latest version Share on Acute anaphylactic and multiorgan inflammatory effects of Comirnaty in pigs Authors : Laszlo Dezsi , Gabor Kokeny , Gabor Szenasi , Csaba Revesz , Tamas Meszaros , Bálint Barta , Reka Facsko , … Show All … , Anna Szilasi , Tamas Bakos , Gergely Kozma , Attila Dobos , Bela Merkely , Tamás Radovits , and Janos Szebeni [email protected] Show Fewer Authors Info & Affiliations https://doi.org/10.22541/au.175033364.42193669/v1 220 views 124 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background and Purpose Rare but serious adverse events (AEs) associated with mRNA-lipid nanoparticle (LNP) COVID-19 vaccines, such as Comirnaty and Spikevax, include acute and chronic inflammatory reactions, the mechanisms of which remain poorly understood. This study aimed to investigate these effects using a porcine model. Experimental Approach Naïve and anti-PEG antibody-sensitized pigs were intravenously injected with Comirnaty. Acute anaphylactic responses were assessed through hemodynamic monitoring, hematological changes, and plasma inflammatory markers. Multiorgan inflammatory effects were evaluated by qPCR detection of spike protein (SP) mRNA uptake and inflammatory cytokine gene expression in seven organs over 6 hours. Histopathology and immunohistochemistry were also performed. Results Severe cardiopulmonary distress developed within minutes of repeated i.v. injections of Comirnaty. qPCR revealed predominant SP mRNA accumulation in liver and PBMCs, with spleen, kidney, lymph nodes, heart, and brain also affected in 40–90% of animals. Repetitive PBMC transfection showed reversible mRNA peaks at 15 minutes, followed by rapid decay. Expression of proinflammatory cytokines (IL-1RA, CXCL10, TNF-α, CCL2) paralleled mRNA uptake, suggesting a causal relationship. Cytokine profiles varied by organ (e.g. IL-1RA in kidney, CCL2 in PBMCs). Histologic abnormalities and SP immunopositivity were noted in kidney, heart, and brain. Booster injections replicated PBMC transfection kinetics observed at first dose. Conclusions and Implications This porcine model reveals systemic anaphylactic reactivity and multiorgan SP mRNA transfection following i.v. injection of mRNA-LNPs, resulting in organ-specific inflammatory responses. These findings provide mechanistic insights into the rare vaccine-related AEs and may support future efforts to improve the safety of the mRNA-LNP platform. Supplementary Material File (dezsi et al., bjp june 6, 2025.docx) Download 19.92 MB Information & Authors Information Version history V1 Version 1 19 June 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Laszlo Dezsi Semmelweis University View all articles by this author Gabor Kokeny Semmelweis University View all articles by this author Gabor Szenasi Semmelweis University View all articles by this author Csaba Revesz Semmelweis University View all articles by this author Tamas Meszaros Seroscience LLC View all articles by this author Bálint Barta Semmelweis University View all articles by this author Reka Facsko Semmelweis University View all articles by this author Anna Szilasi University of Veterinary Medicine View all articles by this author Tamas Bakos Semmelweis University View all articles by this author Gergely Kozma Semmelweis University View all articles by this author Attila Dobos Semmelweis University View all articles by this author Bela Merkely Semmelweis University View all articles by this author Tamás Radovits Semmelweis University View all articles by this author Janos Szebeni [email protected] Semmelweis University View all articles by this author Metrics & Citations Metrics Article Usage 220 views 124 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Laszlo Dezsi, Gabor Kokeny, Gabor Szenasi, et al. Acute anaphylactic and multiorgan inflammatory effects of Comirnaty in pigs. Authorea . 19 June 2025. DOI: https://doi.org/10.22541/au.175033364.42193669/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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