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Allergenic components of the mRNA-1273 vaccine for COVID-19: Possible involvement of polyethylene glycol and IgG-mediated complement activation
Authors:Ludger Klimek  Natalija Novak  Beatriz Cabanillas  Marek Jutel  Jean Bousquet  Cezmi A. Akdis
Affiliation:1. Center for Rhinology and Allergology, Wiesbaden, Germany;2. Department of Dermatology and Allergy, University Hospital, Bonn, Germany;3. Department of Allergy, Research Institute Hospital 12 de Octubre, Madrid, Spain;4. Department of Clinical Immunology, Wrocław Medical University, Poland, ALL-MED Medical research Institute, Wroclaw, Poland;5. Comprehensive Allergy Center, Department of Dermatology and Allergy, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany;6. Swiss Institute of Allergy and Asthma Research (SIAF, University of Zurich, Davos, Switzerland
Abstract:Following the emergency use authorization of the mRNA-1273 vaccine on the 18th of December 2020, two mRNA vaccines are in current use for the prevention of coronavirus disease 2019 (COVID-19). For both mRNA vaccines, the phase III pivotal trials excluded individuals with a history of allergy to vaccine components. Immediately after the initiation of vaccination in the United Kingdom, Canada, and the United States, anaphylactic reactions were reported. While the culprit trigger requires investigation, initial reports suggested the excipient polyethylene glycol 2000 (PEG-2000)—contained in both vaccines as the PEG-micellar carrier system—as the potential culprit. Surface PEG chains form a hydrate shell to increase stability and prevent opsonization. Allergic reactions to such PEGylated lipids can be IgE-mediated, but may also result from complement activation-related pseudoallergy (CARPA) that has been described in similar liposomes. In addition, mRNA-1273 also contains tromethamine (trometamol), which has been reported to cause anaphylaxis to substances such as gadolinium-based contrast media. Skin prick, intradermal and epicutaneous tests, in vitro sIgE assessment, evaluation of sIgG/IgM, and basophil activation tests are being used to demonstrate allergic reactions to various components of the vaccines.
Keywords:COVID  SARS-CoV  vaccines
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