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 vaccine mRNA-1273 on
18th December 2020 in the US and the vaccine BNT162b2 one week earlier,
two mRNA vaccines are in currently used for the prevention of
coronavirus disease 2019 (COVID-19). Phase 3 pivotal trials on both
vaccines excluded individuals with a history of allergy to vaccine
components. Immediately after the initiation of vaccination in the
United Kingdom, Canada, and in the US, anaphylactic reactions have been
reported. While the culprit trigger requires investigation, initial
reports suggested the excipient polyethylene glycol 2000 (PEG-2000),
which is contained in both vaccines as 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
PEG-ylated lipids are rarely IgE-mediated, but may result from
complement activation-related pseudoallergy (CARPA) that has been
described to similar liposomes. In addition, mRNA-1273 also contains
tromethamine (trometamol), which has been reported to cause anaphylaxis
to e.g. gadolinium-based or iodinated contrast media. Skin prick-,
intradermal-, epicutaneous- tests, in vitro sIgE assessment, evaluation
of sIgG/IgM, as well as basophil activation test are in use to
demonstrate allergic reactions to various components of the vaccines.