PhD Scientific Days 2025

Poster Session II. - U: Cardiovascular Medicine and Research

Hemodynamics and Proteomics in Anaphylactic Shock Induced by the COVID-19 mRNA Vaccine Comirnaty in an Anti-PEG Hyperimmune Large Animal Model

Name of the presenter

Barta Bálint András

Institute/workplace of the presenter

Scientific Research Laboratory, Heart and Vascular Center, Semmelweis University, Budapest, Hungary

Authors

Balint Andras Barta¹, Tamás Radovits¹, Attila Balázs Dobos¹, Gergely Tibor Kozma², Tamás Mészáros², Petra Berényi², Réka Facskó², Béla Merkely¹, János Szebeni²

1: Scientific Research Laboratory, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
2: Nanomedicine Research and Education Center, Department of Translational Medicine, Semmelweis University, Budapest, Hungary

Text of the abstract

Background: COVID-19 mRNA vaccines containing polyethylene glycol (PEG) can cause hypersensitivity reactions (HSRs), including rare anaphylaxis. The role of anti-PEG antibodies (Abs) has been proposed but not proven in an animal model.

Purpose: We used an anti-PEG hyperimmune porcine model (Doxebo) to show causality and investigate complement activation, thromboxane A₂ release, and plasma proteome changes.

Methods: Six pigs were immunized IV with 0.1 mg/kg Doxebo. Two to three weeks later, each received one-third of the human Pfizer COVID-19 mRNA vaccine (Comirnaty). Hemodynamic, hematologic, and immune mediator changes were measured, including pulmonary arterial pressure (PAP), systemic arterial pressure (SAP), C3a, and thromboxane B₂ (TXB₂). Explorative plasma LC-MS/MS proteomics was conducted at −1, 1, 3, 5, 10, and 30 minutes post-injection, followed by partial least squares discriminant analysis (PLSDA) and differential expression analysis (DEA).

Results: Anti-PEG IgM levels rose 5,000- to 10,000-fold. All pigs developed anaphylactic shock within two minutes, four requiring resuscitation. Pulmonary hypertension (PAP 13±2 to 37±6 mmHg, median±MAD, p<0.05), severe hypotension (SAP 63±8 to 42±11 mmHg, p<0.05), tachycardia, granulocytopenia, thrombocytopenia, and skin rash were noted. C3a and TXB₂ rose. PLSDA showed that complement depletion was the main driver, while matricellular proteins increased in plasma based on DEA.

Conclusion: This is the first large animal model of mRNA vaccine-induced anaphylaxis. Our data confirm the causal role of anti-PEG Abs and complement activation, representing a CARPA reaction. The proteomic analyses underscore complement depletion and upregulation of matricellular proteins.

Funding: HU-RIZONT-59, 2022-1.1.1-KK-2022-00005, K134939, EKÖP-2024-12, RRF-2.3.1-21-2022-00003, TKP2021-EGA-23