SA Pathology, Adelaide, Australia.
SA Pathology, Adelaide, Australia; School of Biological Sciences, University of Adelaide, Adelaide, Australia.
J Allergy Clin Immunol. 2021 Jul;148(1):91-95. doi: 10.1016/j.jaci.2021.04.032. Epub 2021 May 12.
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.
导致对 BNT162b2（辉瑞）COVID-19 疫苗过敏的机制尚不清楚，脂质纳米颗粒中含有的聚乙二醇（PEG）被怀疑是罪魁祸首。
我们旨在评估皮肤试验和嗜碱性粒细胞活化试验在 PEG、聚山梨酯 80 以及 BNT162b2（辉瑞）和 AZD1222（阿斯利康）COVID-19 疫苗过敏史患者中的表现。
招募了三名已知的 PEG 过敏患者和三名健康对照者，通过皮肤试验和嗜碱性粒细胞活化试验评估对 BNT162b2 和 AZD1222 疫苗以及相关化合物的过敏反应，通过流式细胞术测量 CD63 上调来衡量嗜碱性粒细胞的活化。
我们发现 BNT162b2 疫苗可诱导 PEG 过敏患者的皮肤试验阳性，而在 3 名患者中的 2 名中，传统的 PEG 皮肤试验结果为阴性。一名患者由于 PEG 和聚山梨酯过敏的交叉反应，被发现同时对 BNT162b2 和 AZD1222 疫苗过敏。BNT162b2 疫苗，但不是单独的 PEG，可在体外诱导所有患者的嗜碱性粒细胞的剂量依赖性活化。PEG 化脂质体阿霉素也可诱导相似的嗜碱性粒细胞活化，表明纳米颗粒中 PEG 化的脂质，而不是其天然状态的 PEG，能够有效地诱导脱颗粒。
我们的研究结果表明，作为共价修饰和排列在疫苗脂质纳米颗粒上的 PEG，可能是对 BNT162b2 反应性过敏的潜在触发因素，并突出了目前用于 PEG 化脂质体药物过敏的皮肤试验方案的局限性。
