Serum polyethylene glycol-specific IgE and IgG in patients with hypersensitivity to COVID-19 mRNA vaccines

Hypersensitivity reactions to anti-SARS-CoV-2 vaccines: Basophil reactivity to excipients

“…Canonical IgE-mediated allergic responses to PEG were first claimed as potential causes of inflammatory adverse events in patients receiving anti-SARS-CoV-2 vaccines. In contrast to this hypothesis, limited evidence has so far been acquired on clinically relevant anti-PEG IgE in association with vaccine-related allergic events [14] , [15] , [16] , [37] . Furthermore, vaccination occurs uneventfully in patients with established allergy to PEG [19] , suggesting that either a) lipid-bound PEG rather than “naked” PEG might be the target antigen of canonical IgE-mediated allergic responses to anti-SARS-CoV-2 vaccines and/or that; b) non-IgE-mediated mechanisms might be involved in anti-SARS-CoV-2 vaccine hypersensitivity.…”

“…Due to existing literature on PEG-related allergy and the widespread sources of potential sensitisation among commonly used drugs and cosmetics in the general population, PEG was first proposed as a potential culprit agent for anti-SARS-CoV-2 vaccine-related hypersensitivity reactions [12] , [13] , [14] . The PEG-2000 hypothesis is further corroborated by the detection of circulating anti-PEG IgG and IgE in humans [14] , [15] , [16] and by the potential association between anti-SARS-CoV-2 mRNA-based vaccine hypersensitivity and positive skin prick or intradermal tests with PEG [17] , [18] . Nevertheless, anti-PEG antibodies are apparently not correlated with the occurrence of hypersensitivity reactions [19] and the rate of positive skin prick tests to PEG is low, especially without accurate pre-test stratification [10] , [17] , [20] .…”

Evaluation of association of anti-PEG antibodies with anaphylaxis after mRNA COVID-19 vaccination

“…Anti-PEG IgE was not detected in a patient described as having had a severe allergic reaction requiring hospitalization following mRNA COVID-19 vaccination. [22] However, Mouri et al [23] detected anti-PEG IgE using an ELISA assay in a patient with Brighton level 3 anaphylaxis after Pfizer-BioNTech vaccination, as well as in other patients with immediate non-anaphylactic and delayed reactions following mRNA COVID-19 vaccines. In their study, anti-PEG IgE levels in the immediate reaction group were higher than in the control group (all Pfizer-BioNTech recipients); some controls were anti-PEG IgE positive.…”

Ionizable Lipid Nanoparticles for mRNA Delivery

“…[82] The toxicity may increase mildly with increasing alkyl chain length in the hydrophobic tail. [83] The immunogenicity of iLNP is mainly caused by PEGylated lipids, [84] since PEGylated lipids may interact with immune cells to generate adverse antibodies. [85] The risk of thrombosis may be weakened using ionizable lipids instead of cationic lipids because the iLNP based on ionizable lipids is neutral in the physiological environment, which may reduce the formation of anionic protein corona.…”

“…[ 82 ] The toxicity may increase mildly with increasing alkyl chain length in the hydrophobic tail. [ 83 ] The immunogenicity of iLNP is mainly caused by PEGylated lipids, [ 84 ] since PEGylated lipids may interact with immune cells to generate adverse antibodies. [ 85 ]…”