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001-es BibID:	BIBFORM117391
035-os BibID:	(Scopus)85124573206
Első szerző:	Dézsi László
Cím:	A naturally hypersensitive porcine model may help understand the mechanism of COVID-19 mRNA vaccine-induced rare (pseudo) allergic reactions : complement activation as a possible contributing factor / László Dézsi, Tamás Mészáros, Gergely Kozma, Mária H-Velkei, Csaba Zs. Oláh, Miklós Szabó, Zsófia Patkó, Tamás Fülöp, Mark Hennies, Miklós Szebeni, Bálint András Barta, Béla Merkely, Tamás Radovits, János Szebeni
Dátum:	2022
ISSN:	2509-2715 2509-2723
Megjegyzések:	A tiny fraction of people immunized with lipid nanoparticle (LNP)-enclosed mRNA (LNP-mRNA) vaccines develop allergic symptoms following their first or subsequent vaccinations, including anaphylaxis. These reactions resemble complement (C) activation-related pseudoallergy (CARPA) to i.v. administered liposomes, for which pigs provide a naturally oversensitive model. Using this model, we injected i.v. the human vaccination dose (HVD) of BNT162b2 (Comirnaty, CMT) or its 2-fold (2x) or 5-fold (5x) amounts and measured the hemodynamic changes and other parameters of CARPA. We observed in 6 of 14 pigs transient pulmonary hypertension along with thromboxane A2 release into the blood and other hemodynamic and blood cell changes, including hypertension, granulocytosis, lymphopenia, and thrombocytopenia. One pig injected with 5x CMT developed an anaphylactic shock requiring resuscitation, while a repeat dose failed to induce the reaction, implying tachyphylaxis. These typical CARPA symptoms could not be linked to animal age, sex, prior immune stimulation with zymosan, immunization of animals with Comirnaty i.v., or i.m. 2 weeks before the vaccine challenge, and anti-PEG IgM levels in Comirnaty-immunized pigs. Nevertheless, IgM binding to the whole vaccine, used as antigen in an ELISA, was significantly higher in reactive animals compared to non-reactive ones. Incubation of Comirnaty with pig serum in vitro showed significant elevations of C3a anaphylatoxin and sC5b-9, the C-terminal complex. These data raise the possibility that C activation plays a causal or contributing role in the rare HSRs to Comirnaty and other vaccines with similar side effects. Further studies are needed to uncover the factors controlling these vaccine reactions in pigs and to understand their translational value to humans
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Anaphylatoxins CARPA Complement COVID-19 Hemodynamic changes Pigs Pseudoallergy Shock
Megjelenés:	GeroScience. - 44 : 2 (2022), p. 597-618. -
További szerzők:	Mészáros Tamás Kozma Gergely H-Velkei Mária Oláh Csaba (1972-) (idegsebész) Szabó Miklós (1980-) (tüdőgyógyász) Patkó Zsófia Fülöp Tamás Hennies, Mark Szebeni Miklós Barta Bálint András Merkely Béla (1965-) (orvos) Radovits Tamás Szebeni János
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