The new COVID-19 vaccines by Pfizer/BioNTech and Moderna contain polyethylene glycol (PEG), a common ingredient in skin care products and laxatives. Anti-PEG antibodies are found in people who have been exposed to PEG. Upon re-exposure, those antibodies can elicit an immune response with effects that range from mild to severe.
In the study below, 72% of contemporary human samples contained anti-PEG antibodies. That’s a lot! The authors advise screening patients prior to “administration of therapeutics containing PEG.”
Analysis of Pre-Existing IgG and IgM Antibodies Against Polyethylene Glycol (PEG) In The General Population, Analytical Chemistry, December 2016
Circulating antibodies (Ab) that specifically bind polyethylene glycol (PEG), a biocompatible polymer routinely used in protein and nanoparticle therapeutics, have been associated with reduced efficacy of and/or adverse reactions to therapeutics modified with or containing PEG.
Unlike most antidrug antibodies that are induced following initial drug dosing, anti-PEG Ab can be found in treatment-naïve individuals (i.e., individuals who have never undergone treatment with PEGylated drugs but most likely have been exposed to PEG through other means).
Unfortunately, the true prevalence, quantitative levels, and Ab isotype of pre-existing anti-PEG Ab remain poorly understood. Here, using rigorously validated competitive ELISAs with engineered chimeric anti-PEG monoclonal Ab standards, we quantified the levels of anti-PEG IgM and different subclasses of anti-PEG IgG (IgG1-4) in both contemporary and historical human samples.
We unexpectedly found, with 90% confidence, detectable levels of anti-PEG Ab in ∼72% of the contemporary specimens (18% IgG, 25% IgM, 30% both IgG and IgM).
Anti-PEG Ab’s were also observed in ∼56% of serum samples collected during 1970-1999 (20% IgG, 19% IgM, and 16% both IgG and IgM), suggesting that the presence of PEG-specific antibodies may be a longstanding phenomenon.
The widespread prevalence of pre-existing anti-PEG Ab, coupled with high Ab levels in a subset of the population, underscores the potential importance of screening patients for anti-PEG Ab levels prior to administration of therapeutics containing PEG.
Having anti-PEG antibodies can lead to another unwanted effect. Those antibodies can attack the vaccine (PEG is used as a coating to keep the vaccine from degrading), resulting in reduced vaccine effectiveness:
“… it is increasingly recognized that treating patients with PEGylated drugs can lead to the formation of antibodies that specifically recognize and bind to PEG (i.e., anti-PEG antibodies). Anti-PEG antibodies are also found in patients who have never been treated with PEGylated drugs but have consumed products containing PEG. Consequently, treating patients who have acquired anti-PEG antibodies with PEGylated drugs results in accelerated blood clearance, low drug efficacy, hypersensitivity, and, in some cases, life-threatening side effects.”
– The Importance Of Poly(ethylene glycol) Alternatives For Overcoming PEG Immunogenicity In Drug Delivery And Bioconjugation, Polymers, February 2020