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

Előadó neve

Dr. Barta Balint Andras

Neptun code

DQSKV5

Előadó munkahelye

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

Előadó telefonszáma

+36307257131

Előadó e-mail címe

barta.balint@gmail.com

Az előadás címe

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

Szerző(k) neve és munkahelye

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

Bemutatás módja

Poszter

Szekció

Poster Session II. - U: Cardiovascular Medicine and Research

Language of the presentation

English

Preferred session

Cardiovascular Medicine and Research

Összefoglaló szövege

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

University

Semmelweis University

Supervisor

Prof. Tamás Radovits MD, PhD

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

5886

Start

18:36

End

18:42