Allergenic components of the mRNA‐1273 vaccine for COVID‐19: possible involvement of polyethylene glycol and IgG‐mediated complement activation

ABSTRACT

Following the emergency use authorization of the mRNA‐1273 vaccine on the 18 ^thof December2020,two mRNAvaccinesare in current use for the prevention of coronavirus disease 2019 (COVID‐19). For both mRNA vaccines, the phase IIIpivotal trials excluded individuals with a history of allergy tovaccine components.Immediately after the initiation of vaccination in the United Kingdom, Canada, and the US, 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 potentialculprit. Surface PEG chains form a hydrate shell to increasestability and prevent opsonization. Allergic reactions to such PEGylated lipids can be IgE‐mediated,but may alsoresult from complement activation‐related pseudoallergy (CARPA) that has been described insimilar liposomes. In addition, mRNA‐1273 also contains tromethamine (trometamol), which has been reported to cause anaphylaxis to substances such asgadolinium‐based contrast media.

Skin prick, intradermal and epicutaneoustests, in vitro sIgE assessment, evaluation ofsIgG/IgM,as well as basophil activation tests are being used to demonstrate allergic reactions to various components of the vaccines.