The excipient polyethylene glycol (PEG) contained in the mRNA vaccines for COVID-19 has been pointed out as one of the possible triggers of the hypersensitivity reactions that have been described since the beginning of the vaccine campaigns for COVID-19 protection.1 However, PEG is not present in the mRNA vaccines in an isolated form but in conjugation with lipid-nanoparticles (LNPs), which are spherical vesicles constituted by ionizable lipids, thanks to a process called PEGylation, which could potentially alter the immunogenic properties of PEG. PEG coats the surface of the LNPs reducing opsonization, aggregation, and improving mRNA delivery to the target cells.
The form of PEG matters: PEG conjugated with lipids and not PEG alone could be the specific form involved in allergic reactions to COVID-19 vaccines.