Abstract
Background
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.
Objectives
To evaluate PEGylated lipid nanoparticle (LNP) vaccine (BNT162b2) tolerance, and explore the mechanism of reactivity in PEG and/or PS80 allergic patients.
Methods
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).
Results
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.
Conclusion
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.
Keywords: basophil activation test, polyethylene glycol, polysorbate 80, BNT162b2, ALC-0159, SARS-CoV-2, vaccine, allergy, IgE, cross-reactivity
Graphical abstract
Footnotes
Funding sources:
DB and RS are supported by the Fonds Wetenschappelijk Onderzoek - Vlaanderen National Fund for Scientific Research (FWO) senior clinical investigator fellowship (1805518N, 1805523N; and 1801019N). The study was supported by UZ Leuven KOOR funding (S60734). The funder(s) had no role in the design and conduct of the study, collection, management, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Conflict of interest statement:
All authors declare that they have no conflicts of interest to disclose.
Abbreviations: AC: anaphylaxis control; BAT: basophil activation testing; CARPA: complement activation-related pseudoallergy; cd-BAT: complement-deprived basophil activation test; CDC: Centers for Disease Control and Prevention; DA: dual-allergy; DEG: diethylene glycol; EG: ethylene glycol; GVC: graded vaccine challenge; HC: healthy control; HDM: house dust mite; HMW: high molecular weight; LMW: low molecular weight; LNP: lipid nanoparticle; MW: molecular weight; PEG: polyethylene glycol; PS80: polysorbate 80; SEM: standard error of mean; sIgE: specific IgE; ST: skin test; tIgE: total IgE; wb-BAT: whole blood basophil activation test