Title : Mast cell degranulation links anti-PEG IgE to anaphylaxis caused by PEGylated drugs and PEG-contained LNP/mRNA COVID vaccines
Abstract:
Polyethylene glycol (PEG)- modification (PEGylation) is a highly successful strategy for improving the therapeutic properties of protein products. PEGylation increases protein size, inhibits proteolysis and decreases renal filtration, thereby improving the pharmacokinetics (half-life) of the protein drugs. PEG is also a critical component to stabilize lipid nano particle (LNP)-based therapeutics. Despite the success in achieving improved pharmacokinetics, PEGylated drugs have a small but significant rate (from less than 0.1% up to 9%) of acute allergic reactions, many upon first treatment with the PEGylated drug. LNP/mRNA based COVID Vaccines have also reported higher rates of allergic reactions than general vaccinations. While the rate may be low, allergic reactions, particularly anaphylaxis, can be life-threatening. In some cases, the frequency of severe reactions is high enough to withdraw an otherwise promising drug from the marketplace. In the investigation of the root cause of allergic reactions to a PEGylated drug, our lab established a sensitive method to accurately detect pre-existing immunogenicity to the PEG component of these products. In this presentation, I will discuss our new lab evidence of mast cell degranulation that links anti-PEG IgE to anaphylaxis caused by PEGylated Drugs and PEG-contained LNP/mRNA COVID vaccines.
Audience Take Away:
- PEGylated drug and PEG-contained COVID vaccine-associated anaphylaxis could be due to IgE-mediated type 1 hypersensitivity
- DCBA assay with its unique sensitivity and specificity designing can accurately detect anti-PEG IgE
- Evidence of Type I hypersensitivity demonstrated by specific IgE-mediated mast cell degranulation upon PEG and vaccine exposure
