Endotyping of IgE-mediated polyethylene glycol and/or polysorbate 80 allergy.

Publication date: Jun 26, 2023

Polyethylene glycol (PEG) and polysorbate 80 (PS80) allergy preclude from SARS-CoV-2 vaccination. The mechanism(s) governing cross-reactivity and PEG molecular weight-dependency remain unclear. To evaluate PEGylated lipid nanoparticle (LNP) vaccine (BNT162b2) tolerance, and explore the mechanism of reactivity in PEG and/or PS80 allergic patients. PEG/PS80 dual- (n=3), PEG mono- (n=7) and PS80 mono-allergic patients (n=2) were included. Tolerability of graded vaccine challenges was assessed. Basophil activation testing on whole blood (wb-BAT) or passively sensitized donor basophils (allo-BAT) was performed using PEG, PS80, BNT162b2, and PEGylated lipids (ALC-0159). Serum PEG-specific IgE was measured in patients (n=10) and controls (n=15). Graded BNT162b2 challenge in dual- and PEG mono-allergic patients (n=3/group) was well-tolerated and induced anti-S IgG seroconversion. PS80 mono-allergic patients (n=2/2) tolerated single-dose BNT162b2 vaccination. Wb-BAT reactivity to PEG-containing antigens was observed in dual- (n=3/3) and PEG mono- (n=2/3), but absent in PS80 mono-allergic patients (n=0/2). BNT162b2 elicited the highest in vitro reactivity. BNT162b2 reactivity was IgE-mediated, complement-independent, and inhibited in allo-BAT by preincubation with short PEG motifs, or detergent-induced LNP degradation. PEG-specific IgE was only detectable in dual-allergic (n=3/3) and PEG mono-allergic (n=1/6) serum. PEG and PS80 cross-reactivity is determined by IgE recognizing short PEG motifs, whilst PS80 mono-allergy is PEG-independent. PS80 skin test positivity in PEG allergics was associated with a severe and persistent phenotype, higher serum PEG-specific IgE levels and enhanced BAT reactivity. Spherical PEG-exposure via LNP enhances BAT sensitivity through increased avidity. All PEG and/or PS80 excipient allergic patients can safely receive SARS-CoV-2 vaccines.

Concepts Keywords
Allergic ALC-0159
Bnt162b2 allergy
Nanoparticle basophil activation test
Vaccination BNT162b2
polyethylene glycol
polysorbate 80


Type Source Name
drug DRUGBANK Polyethylene glycol
drug DRUGBANK Polysorbate 80
disease MESH allergy
disease VO vaccination
disease VO vaccine
disease MESH seroconversion
disease VO dose

Original Article

(Visited 1 times, 1 visits today)

Leave a Comment

Your email address will not be published. Required fields are marked *