https://m2.mtmt.hu/ hun 2026-05-31 11:21 JournalArticle 34754128 VALIDATED true Nanomedicine Research and Education Center, Department of Translational Medicine, Semmelweis University, Budapest, 1085, Hungary SeroScience LCC., Budapest, 1089, Hungary Department of Cardiology, Heart and Vascular Center, Semmelweis University, Budapest, 1122, Hungary Department of Surgical Research and Techniques, Heart and Vascular Center, Semmelweis University, Budapest, 1089, Hungary Hungarian Center of Reference and Excellence, Department of Internal Medicine and Hematology, Semmelweis University, Budapest, 1088, Hungary Etherna Biopharmaceuticals, Niel, 2845, Belgium Division of Laboratories and Pharmacy, University Medical Center, Utrecht, 3584 CX, Netherlands Department of Education, Gratz College, Philadelphia, PA 19027, United States Department of Nanobiotechnology and Regenerative Medicine, Faculty of Health Sciences, Miskolc University, Miskolc, 3530, Hungary Translational Nanobioscience Research Center, Sungkyunkwan University, Suwon, 06351, South Korea Export Date: 16 May 2024 Correspondence Address: Szebeni, J.; Nanomedicine Research and Education Center, Hungary; email: szebeni.janos@med.semmelweis-univ.hu 0 false 2026-05-23T16:27:07.890+0000 2024-05-03T11:13:42.732+0000 2024-03-25T08:20:34.023+0000 true 10069606 Pintér Ibolya Katalin /api/admin/10069606 Admin true 2026-02-04T14:32:45.693+0000 2024-05-03T11:13:43.117+0000 true 10015546 Berhidi Anna /api/admin/10015546 Admin true 10015546 true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Bakos, Tamás mRNA-LNP COVID-19 Vaccine Lipids Induce Complement Activation and Production of Proinflammatory Cytokines: Mechanisms, Effects of Complement Inhibitors, and Relevance to Adverse Reactions true true /api/journal/10003252 REVIEWED true false 10003252 false 10003252 true 1661-6596 1422-0067 Journal FOREIGN 25 7 3595 3595 17 2024 A small fraction of people vaccinated with mRNA–lipid nanoparticle (mRNA-LNP)-based COVID-19 vaccines display acute or subacute inflammatory symptoms whose mechanism has not been clarified to date. To better understand the molecular mechanism of these adverse events (AEs), here, we analyzed in vitro the vaccine-induced induction and interrelations of the following two major inflammatory processes: complement (C) activation and release of proinflammatory cytokines. Incubation of Pfizer-BioNTech’s Comirnaty and Moderna’s Spikevax with 75% human serum led to significant increases in C5a, sC5b-9, and Bb but not C4d, indicating C activation mainly via the alternative pathway. Control PEGylated liposomes (Doxebo) also induced C activation, but, on a weight basis, it was ~5 times less effective than that of Comirnaty. Viral or synthetic naked mRNAs had no C-activating effects. In peripheral blood mononuclear cell (PBMC) cultures supplemented with 20% autologous serum, besides C activation, Comirnaty induced the secretion of proinflammatory cytokines in the following order: IL-1α < IFN-γ < IL-1β < TNF-α < IL-6 < IL-8. Heat-inactivation of C in serum prevented a rise in IL-1α, IL-1β, and TNF-α, suggesting C-dependence of these cytokines’ induction, although the C5 blocker Soliris and C1 inhibitor Berinert, which effectively inhibited C activation in both systems, did not suppress the release of any cytokines. These findings suggest that the inflammatory AEs of mRNA-LNP vaccines are due, at least in part, to stimulation of both arms of the innate immune system, whereupon C activation may be causally involved in the induction of some, but not all, inflammatory cytokines. Thus, the pharmacological attenuation of inflammatory AEs may not be achieved via monotherapy with the tested C inhibitors; efficacy may require combination therapy with different C inhibitors and/or other anti-inflammatory agents. Funding 2039497 /api/funding/2039497 false true Funding 2039498 /api/funding/2039498 false true Funding 2039499 /api/funding/2039499 false true true true 2024 true true true false true false GOLD 2026-05-23 true https://doi.org/10.3390/ijms25073595 30 0 29 24 6 28 29 28 25 28 28 23 23 24 6 0 30 24 29 24 0 15 15 Folyóiratcikk Journal Article 24 28 Könyvrészlet Chapter in Book 25 1 Könyv Book 23 0 Egyéb konferenciaközlemény Conference paper 31 0 Egyéb konferenciakötet Conference proceedings 32 0 Oltalmi formák Protection forms 26 0 Disszertáció Thesis 28 0 Egyéb Miscellaneous 29 1 Alkotás Achievement 22 0 Kutatási adat Research data 33 0 Folyóiratcikk Journal Article 24 0 0 0 Könyvrészlet Chapter in Book 25 0 0 0 Könyv Book 23 0 0 0 Egyéb konferenciaközlemény Conference paper 31 0 0 0 Egyéb konferenciakötet Conference proceedings 32 0 0 0 Oltalmi formák Protection forms 26 0 0 0 Disszertáció Thesis 28 0 0 0 Egyéb Miscellaneous 29 0 0 0 Alkotás Achievement 22 0 0 0 Kutatási adat Research data 33 0 0 0 2024 0 5 4 5 4 2025 0 20 15 20 15 2026 0 5 5 5 5 D1 false 10027489 false false false 2024-04-23T10:59:31.266+0000 Belgyógyászati és Hematológiai Klinika (SE / AOK / K); Elméleti Egészségtudományok Intézete (ME / ETK); Kardiológia Központ - Kardiológiai Tanszék (SE / AOK / K); Kísérletes és Sebészeti Műtéttani Tanszék (SE / AOK / K); Nanomedicina Kutató és Oktató Központ (SE / AOK / I / KKI); Transzlációs Medicina Intézet (SE / AOK / I) 9 38 6 14 0 true Language 10002 /api/language/10002 Angol English true 2 true PersonAuthorship 115907736 /api/authorship/115907736 1 0.071 true false false Author 10070223 /api/author/10070223 Bakos Tamás true true Bakos Tamás true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 115907737 /api/authorship/115907737 2 0.071 true false false Author 10064003 /api/author/10064003 Mészáros Tamás true 10064003 true Mészáros Tamás true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 115907738 /api/authorship/115907738 3 0.071 false false false Author 10024742 /api/author/10024742 Kozma Gergely Tibor true 10024742 true Kozma Gergely Tibor true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 115907739 /api/authorship/115907739 4 0.071428575 false false false Berényi Petra true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 115907740 /api/authorship/115907740 5 0.071 false false false Author 10083173 /api/author/10083173 Facskó Réka true true Facskó Réka true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 115907741 /api/authorship/115907741 6 0.071 false false false Author 10009711 /api/author/10009711 Farkas Henriette true 10009711 true Farkas Henriette true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 115907742 /api/authorship/115907742 7 0.071 false false false Author 10005165 /api/author/10005165 Dézsi László true 10005165 true Dézsi László true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 115907743 /api/authorship/115907743 8 0.071428575 false false false Heirman Carlo true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 115907744 /api/authorship/115907744 9 0.071428575 false false false de Koker Stefaan true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 115907745 /api/authorship/115907745 10 0.071428575 false false false Schiffelers Raymond true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 115907746 /api/authorship/115907746 11 0.071428575 false false false Glatter Kathryn Anne true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 115907747 /api/authorship/115907747 12 0.071 false false false Author 10013969 /api/author/10013969 Radovits Tamás true 10013969 true Radovits Tamás true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 115907748 /api/authorship/115907748 13 0.071 false true false Author 10027489 /api/author/10027489 Szénási Gábor true 10027489 true Szénási Gábor true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 115907749 /api/authorship/115907749 14 0.071 false true true Author 10003266 /api/author/10003266 Szebeni János true 10003266 true Szebeni János true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PublicationIdentifier 25906268 /api/publicationidentifier/25906268 PlainSource 6 /api/publicationsource/6 PublicationSourceType 10001 /api/publicationsourcetype/10001 true true true DOI DOI https://doi.org/@@@ true true 6 true GOLD true IDENTICAL 10.3390/ijms25073595 https://doi.org/10.3390/ijms25073595 false true PublicationIdentifier 26041891 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10.1016/j.ymthe.2022.07.007 false true /api/publication/34754128 <div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" mtid="10070223"><a href="/gui2/?type=authors&mode=browse&sel=10070223" target="_blank">Bakos Tamás (<span class="authorship-author-name">Bakos Tamás</span> <span class="authorAux-mtmt"> Immunológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Transzlációs Medicina Intézet">TMI</span>/Nanomedicina Kutató és Oktató Központ; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Transzlációs Medicina Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10064003"><a href="/gui2/?type=authors&mode=browse&sel=10064003" target="_blank">Mészáros Tamás<sup>*</sup> (<span class="authorship-author-name">Mészáros Tamás</span> <span class="authorAux-mtmt"> nanomedicina</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Transzlációs Medicina Intézet">TMI</span>/Nanomedicina Kutató és Oktató Központ; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Klinikum">K</span>/<span title="Városmajori Szív- és Érgyógyászati Klinika">VAROSMAJOR_SZÍVÉRGYÓGY</span>/Kardiológia Központ - Kardiológiai Tanszék; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Transzlációs Medicina Intézet; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Klinikum">K</span>/<span title="Városmajori Szív- és Érgyógyászati Klinika">VAROSMAJOR_SZÍVÉRGYÓGY</span>/Kísérletes és Sebészeti Műtéttani Tanszék</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10024742"><a href="/gui2/?type=authors&mode=browse&sel=10024742" target="_blank">Kozma Gergely Tibor (<span class="authorship-author-name">Kozma Gergely Tibor</span> <span class="authorAux-mtmt"> Immunológia, Molekuláris biológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Transzlációs Medicina Intézet">TMI</span>/Nanomedicina Kutató és Oktató Központ; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Transzlációs Medicina Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Berényi Petra </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10083173"><a href="/gui2/?type=authors&mode=browse&sel=10083173" target="_blank">Facskó Réka (<span class="authorship-author-name">Facskó Réka</span> <span class="authorAux-mtmt"> elméleti orvostudományok</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Transzlációs Medicina Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10009711"><a href="/gui2/?type=authors&mode=browse&sel=10009711" target="_blank">Farkas Henriette (<span class="authorship-author-name">Farkas Henriette</span> <span class="authorAux-mtmt"> klinikai immunológus, allergológus</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Klinikum">K</span>/Belgyógyászati és Hematológiai Klinika</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10005165"><a href="/gui2/?type=authors&mode=browse&sel=10005165" target="_blank">Dézsi László (<span class="authorship-author-name">Dézsi László</span> <span class="authorAux-mtmt"> Elméleti orvostudományok</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Transzlációs Medicina Intézet">TMI</span>/Nanomedicina Kutató és Oktató Központ; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Transzlációs Medicina Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Heirman Carlo </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >de Koker Stefaan </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Schiffelers Raymond </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Glatter Kathryn Anne </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10013969"><a href="/gui2/?type=authors&mode=browse&sel=10013969" target="_blank">Radovits Tamás (<span class="authorship-author-name">Radovits Tamás</span> <span class="authorAux-mtmt"> kardiológia, érgyógyászat</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Klinikum">K</span>/<span title="Városmajori Szív- és Érgyógyászati Klinika">VAROSMAJOR_SZÍVÉRGYÓGY</span>/Kardiológia Központ - Kardiológiai Tanszék; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Klinikum">K</span>/<span title="Városmajori Szív- és Érgyógyászati Klinika">VAROSMAJOR_SZÍVÉRGYÓGY</span>/Kísérletes és Sebészeti Műtéttani Tanszék</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10027489"><a href="/gui2/?type=authors&mode=browse&sel=10027489" target="_blank">Szénási Gábor<sup>**</sup> (<span class="authorship-author-name">Szénási Gábor</span> <span class="authorAux-mtmt"> kórélettan</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Transzlációs Medicina Intézet">TMI</span>/Nanomedicina Kutató és Oktató Központ; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Transzlációs Medicina Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10003266"><a href="/gui2/?type=authors&mode=browse&sel=10003266" target="_blank">Szebeni János ✉ (<span class="authorship-author-name">Szebeni János</span> <span class="authorAux-mtmt"> Klinikai orvostudomány, immunológia, nanomedicina</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Transzlációs Medicina Intézet">TMI</span>/Nanomedicina Kutató és Oktató Központ; <span title="Miskolci Egyetem">ME</span>/<span title="Egészségtudományi Kar ">ETK</span>/Elméleti Egészségtudományok Intézete; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Transzlációs Medicina Intézet</span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;34754128" target="_blank">mRNA-LNP COVID-19 Vaccine Lipids Induce Complement Activation and Production of Proinflammatory Cytokines: Mechanisms, Effects of Complement Inhibitors, and Relevance to Adverse Reactions</a></div> <div> <span class="journal-title">INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/1661-6596">1661-6596</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1422-0067">1422-0067</a>)</span>: <span class="journal-volume">25</span> <span class="journal-issue">7</span> <span class="page"> Paper 3595. 17 p. </span> <span class="year">(2024)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Nyelv: Angol | </span> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.3390/ijms25073595" target="_blank" href="https://doi.org/10.3390/ijms25073595"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="001201617800001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/001201617800001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85190366289" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85190366289"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="38612407" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=38612407&dopt=Abstract"> PubMed </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Folyóirat szakterülete: Scopus - Organic Chemistry&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Spectroscopy&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Computer Science Applications&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Inorganic Chemistry&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Medicine (miscellaneous)&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Physical and Theoretical Chemistry&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Catalysis&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q2</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Molecular Biology&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q2</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 30</span> | Független: 24 | Függő: 6 | Nem jelölt: 0 | WoS jelölt: 28 | Scopus jelölt:&nbsp;25 | WoS/Scopus jelölt:&nbsp;28 | DOI jelölt:&nbsp;29 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;34754128&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 15 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 34754128</span> | <span class="status-data status-VALIDATED"> Egyeztetett </span> Forrás Idéző | <span class="type-subtype">Folyóiratcikk ( Szakcikk ) </span> | <span class="pub-category">Tudományos</span> | <span class="publication-sourceOfData">kézi felvitel</span> </div> <div class="funder"> (2020-1.1.6-JOVO-2021-00013), (2020-1.1.6-JÖVŐ-2021-00010), (KDP-14-3/PALY-2021) </div> <div class="lastModified">Utolsó módosítás: 2024.05.03. 13:13 Berhidi Anna (SE_KK_Admin5_BA, admin) </div> <pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: Nanomedicine Research and Education Center, Department of Translational Medicine, Semmelweis University, Budapest, 1085, Hungary SeroScience LCC., Budapest, 1089, Hungary Department of Cardiology, Heart and Vascular Center, Semmelweis University, Budapest, 1122, Hungary Department of Surgical Research and Techniques, Heart ...</pre> </div></div>