PEGylated Liposomes for Diagnosis of Polyethylene Glycol Allergy
Journal of Allergy and Clinical Immunology(2024)
摘要
Background
Polyethylene glycol (PEG) is a non-protein polymer that is present in its native (unbound) form as an excipient in a range of products, and is increasingly being utilised clinically in the form of PEGylated liposomal medications and vaccines. PEG is the cause of anaphylaxis in a small percentage of drug reactions, however diagnosis of PEG allergy is complicated by the variable and poor diagnostic performance of current skin testing protocols.
Objective
We assessed the diagnostic performance of PEGylated lipid medications as an alternative to currently described tests that use medications containing PEG excipients.
Methods
Nine patients with a strong history of PEG allergy were evaluated by skin testing with a panel of PEG-containing medications, and with a PEGylated lipid nanoparticle vaccine (BNT162b2). Reactivity of basophils to unbound and liposomal PEG was assessed ex vivo, and specificity of basophil responses to PEGylated liposomes was investigated with a competitive inhibition assay. For detailed Methods, please see the Methods section in this article's Online Repository.
Results
Despite compelling histories of anaphylaxis to PEG-containing medications, only two out of nine patients (22%) returned a positive skin test to purified PEG or their index-reaction indicated PEG-containing compound. Conversely, nine out of nine patients (100%) were skin test positive or basophil activation test positive to PEGylated liposomal BNT162b2 vaccine. Concordantly, PEGylated liposomal drugs (BNT162b2 vaccine and PEGylated liposomal doxorubicin), but not purified PEG2000, consistently induced basophil activation ex vivo in patients with PEG allergy but not in non-allergic controls. Basophil reactivity to PEGylated nanoparticles competitively inhibited by pre-incubation of basophils with native PEG2000.
Conclusion
We demonstrate that presentation of PEG on the surface of a lipid nanoparticle increases its in vivo and ex vivo allergenicity, and improves diagnosis of PEG allergy.
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关键词
PEG allergy,polyethylene glycol,basophil activation,lipid nanoparticle,liposome,allergy diagnosis,vaccination,COVID-19,BNT162b2,mRNA vaccine
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