Alexander Troelnikov1, Griffith Perkins2, Chino Yuson3, Aida Ahamdie4, Summaya Balouch5, Pravin Hissaria6. 1. Immunology Registrar, SA Pathology, Adelaide, South Australia 5000. 2. SA Pathology, Adelaide, South Australia 5000, School of Biological Sciences, University of Adelaide, Adelaide, South Australia 5000. 3. Consultant Immunologist, Immunology Department, Royal Adelaide Hospital, Adelaide, South Australia 5000. 4. Nurse Consultant, Immunology Department, Royal Adelaide Hospital, Adelaide, South Australia 5000. 5. Medical Officer, Immunology Department, Royal Adelaide Hospital, Adelaide, South Australia 5000. 6. Senior Staff Immunologist and Immunopathologist, Immunology Department, Royal Adelaide Hospital, Adelaide, South Australia 5000, SA Pathology, Adelaide, South Australia 5000. Electronic address: pravin.hissaria@sa.gov.au.
Abstract
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: To evaluate the performance of skin testing and basophil activation testing to PEG, polysorbate 80, BNT162b2 and AZD1222 (Astra-Zeneca) COVID-19 vaccines in patients with a history of PEG allergy. METHODS: Three known PEG allergic participants and three healthy controls were recruited, and evaluated for hypersensitivity to the BNT162b2 and AZD1222 vaccines and related compounds by skin testing and basophil activation measured by CD63 upregulation using flow cytometry. RESULTS: We found that the BNT162b2 vaccine induced positive skin tests in PEG allergic patients, whereas traditional PEG skin testing was negative in two of three patients. One patient was found to be co-sensitized to both the BNT162b2 and AZD1222 vaccines due to 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 PEGlyated lipids within nanoparticles, and not PEG in its native state, are able to efficiently induce degranulation. CONCLUSIONS: Our findings implicate PEG, as covalently modified within the vaccine lipid nanoparticle, as a potential trigger of anaphylaxis to BNT162b2.
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: To evaluate the performance of skin testing and basophil activation testing to PEG, polysorbate 80, BNT162b2 and AZD1222 (Astra-Zeneca) COVID-19 vaccines in patients with a history of PEGallergy. METHODS: Three known PEGallergicparticipants and three healthy controls were recruited, and evaluated for hypersensitivity to the BNT162b2 and AZD1222 vaccines and related compounds by skin testing and basophil activation measured by CD63 upregulation using flow cytometry. RESULTS: We found that the BNT162b2 vaccine induced positive skin tests in PEGallergicpatients, whereas traditional PEG skin testing was negative in two of three patients. One patient was found to be co-sensitized to both the BNT162b2 and AZD1222 vaccines due to cross-reactive PEG and polysorbateallergy. 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 PEGlyated lipids within nanoparticles, and not PEG in its native state, are able to efficiently induce degranulation. CONCLUSIONS: Our findings implicate PEG, as covalently modified within the vaccine lipid nanoparticle, as a potential trigger of anaphylaxis to BNT162b2.
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