Basophil reactivity to BNT162b2 is mediated by PEGylated lipid nanoparticles in patients with PEG allergy.
Adult
Anaphylaxis
/ immunology
BNT162 Vaccine
Basophils
/ immunology
COVID-19
/ immunology
COVID-19 Vaccines
/ immunology
Cell Degranulation
Cells, Cultured
ChAdOx1 nCoV-19
Doxorubicin
/ adverse effects
Drug Hypersensitivity
/ immunology
Female
Humans
Lipids
/ chemistry
Male
Middle Aged
Nanoparticles
/ adverse effects
Polyethylene Glycols
/ adverse effects
SARS-CoV-2
/ physiology
Skin Tests
Young Adult
COVID-19
Pfizer BNT162b2
SARS-CoV-2
basophil activation testing
lipid nanoparticles
liposomes
polyethylene glycol and polysorbate allergy
skin testing
vaccine allergy
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
13
04
2021
revised:
22
04
2021
accepted:
28
04
2021
pubmed:
16
5
2021
medline:
20
7
2021
entrez:
15
5
2021
Statut:
ppublish
Résumé
The mechanisms underpinning allergic reactions to the BNT162b2 (Pfizer) COVID-19 vaccine remain unknown, with polyethylene glycol (PEG) contained in the lipid nanoparticle suspected as being the cause. Our aim was to evaluate the performance of skin testing and basophil activation testing to PEG, polysorbate 80, and the BNT162b2 (Pfizer) and AZD1222 (AstraZeneca) COVID-19 vaccines in patients with a history of PEG allergy. Three known individuals with PEG allergy and 3 healthy controls were recruited and evaluated for hypersensitivity to the BNT162b2 and AZD1222 vaccines, and to related compounds by skin testing and basophil activation, as measured by CD63 upregulation using flow cytometry. We found that the BNT162b2 vaccine induced positive skin test results in patients with PEG allergy, whereas the result of traditional PEG skin testing was negative in 2 of 3 patients. One patient was found to be cosensitized to both the BNT162b2 and AZD1222 vaccines because of cross-reactive PEG and polysorbate allergy. The BNT162b2 vaccine, but not PEG alone, induced dose-dependent activation of all patients' basophils ex vivo. Similar basophil activation could be induced by PEGylated liposomal doxorubicin, suggesting that PEGylated lipids within nanoparticles, but not PEG in its native state, are able to efficiently induce degranulation. Our findings implicate PEG, as covalently modified and arranged on the vaccine lipid nanoparticle, as a potential trigger of anaphylaxis in response to BNT162b2, and highlight shortcomings of current skin testing protocols for allergy to PEGylated liposomal drugs.
Sections du résumé
BACKGROUND
The mechanisms underpinning allergic reactions to the BNT162b2 (Pfizer) COVID-19 vaccine remain unknown, with polyethylene glycol (PEG) contained in the lipid nanoparticle suspected as being the cause.
OBJECTIVE
Our aim was to evaluate the performance of skin testing and basophil activation testing to PEG, polysorbate 80, and the BNT162b2 (Pfizer) and AZD1222 (AstraZeneca) COVID-19 vaccines in patients with a history of PEG allergy.
METHODS
Three known individuals with PEG allergy and 3 healthy controls were recruited and evaluated for hypersensitivity to the BNT162b2 and AZD1222 vaccines, and to related compounds by skin testing and basophil activation, as measured by CD63 upregulation using flow cytometry.
RESULTS
We found that the BNT162b2 vaccine induced positive skin test results in patients with PEG allergy, whereas the result of traditional PEG skin testing was negative in 2 of 3 patients. One patient was found to be cosensitized to both the BNT162b2 and AZD1222 vaccines because of cross-reactive PEG and polysorbate allergy. The BNT162b2 vaccine, but not PEG alone, induced dose-dependent activation of all patients' basophils ex vivo. Similar basophil activation could be induced by PEGylated liposomal doxorubicin, suggesting that PEGylated lipids within nanoparticles, but not PEG in its native state, are able to efficiently induce degranulation.
CONCLUSIONS
Our findings implicate PEG, as covalently modified and arranged on the vaccine lipid nanoparticle, as a potential trigger of anaphylaxis in response to BNT162b2, and highlight shortcomings of current skin testing protocols for allergy to PEGylated liposomal drugs.
Identifiants
pubmed: 33991580
pii: S0091-6749(21)00731-4
doi: 10.1016/j.jaci.2021.04.032
pii:
doi:
Substances chimiques
COVID-19 Vaccines
0
Lipids
0
liposomal doxorubicin
0
Polyethylene Glycols
3WJQ0SDW1A
Doxorubicin
80168379AG
ChAdOx1 nCoV-19
B5S3K2V0G8
BNT162 Vaccine
N38TVC63NU
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
91-95Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2021 American Academy of Allergy, Asthma & Immunology. All rights reserved.