Lim Xin Rong, Chan Grace Yin Lai, Tan Justina Wei Lynn, Ng Carol Yee Leng, Chua Choon Guan, Tan Guat Bee, Chan Stephrene Seok Wei, Ong Kiat Hoe, Tan Ying Zhi, Tan Sarah Hui Zhen, Teo Claire Min Li, Lee Samuel Shang Ming, Thong Bernard Yu Hor, Leung Bernard Pui Lam
Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore 308433, Singapore.
Department of Haematology, Tan Tock Seng Hospital, Singapore 308433, Singapore.
Vaccines (Basel). 2023 May 23;11(6):1020. doi: 10.3390/vaccines11061020.
The underlying immunological mechanisms of immediate-type hypersensitivity reactions (HSR) to COVID-19 vaccines are poorly understood. We investigate the mechanisms of immediate-type hypersensitivity reactions to the Pfizer BNT162b2 vaccine and the response of antibodies to the polyethylene glycol (PEG)ylated lipid nanoparticle after two doses of vaccination. Sixty-seven participants, median age 35 and 77.3% females who tolerated two doses of the BNT162b2 vaccine (non-reactors), were subjected to various blood-sampling time points. A separate group of vaccine reactors (10 anaphylaxis and 37 anonymised tryptase samples) were recruited for blood sampling. Immunoglobulin (Ig)G, IgM and IgE antibodies to the BNT162b2 vaccine, biomarkers associated with allergic reaction, including tryptase for anaphylaxis, complement 5a(C5a), intercellular adhesion molecule 1 (ICAM-1) for endothelial activation and Interleukin (IL)-4, IL-10, IL-33, tumour necrosis factor (TNF) and monocyte chemoattractant protein (MCP-1), were measured. Basophil activation test (BAT) was performed in BNT162b2-induced anaphylaxis patients by flow cytometry. The majority of patients with immediate-type BNT162b2 vaccine HSR demonstrated raised C5a and Th2-related cytokines but normal tryptase levels during the acute reaction, together with significantly higher levels of IgM antibodies to the BNT162b2 vaccine (IgM 67.2 (median) vs. 23.9 AU/mL, < 0.001) and ICAM-1 when compared to non-reactor controls. No detectable IgE antibodies to the BNT162b2 vaccine were found in these patients. The basophil activation tests by flow cytometry to the Pfizer vaccine, 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol (DMG-PEG) and PEG-2000 were negative in four anaphylaxis patients. Acute hypersensitivity reactions post BNT162b2 vaccination suggest pseudo-allergic reactions via the activation of anaphylatoxins C5a and are independent of IgE-mechanisms. Vaccine reactors have significantly higher levels of anti-BNT162b2 IgM although its precise role remains unclear.
对新冠疫苗速发型超敏反应（HSR）的潜在免疫机制尚不清楚。我们研究了对辉瑞BNT162b2疫苗速发型超敏反应的机制以及两剂疫苗接种后抗体对聚乙二醇（PEG）化脂质纳米颗粒的反应。67名参与者，年龄中位数为35岁，77.3%为女性，她们耐受两剂BNT162b2疫苗（无反应者），在不同时间点进行采血。另外招募了一组疫苗反应者（10例过敏反应者和37例匿名类胰蛋白酶样本）进行采血。检测了针对BNT162b2疫苗的免疫球蛋白（Ig）G、IgM和IgE抗体，以及与过敏反应相关的生物标志物，包括用于过敏反应的类胰蛋白酶、补体5a（C5a）、用于内皮激活的细胞间黏附分子1（ICAM-1）以及白细胞介素（IL）-4、IL-10、IL-33、肿瘤坏死因子（TNF）和单核细胞趋化蛋白（MCP-1）。通过流式细胞术对BNT162b2诱导的过敏反应患者进行嗜碱性粒细胞激活试验（BAT）。大多数BNT162b2疫苗速发型超敏反应患者在急性反应期间C5a和Th2相关细胞因子升高，但类胰蛋白酶水平正常，与无反应对照相比，针对BNT162b2疫苗的IgM抗体水平也显著更高（IgM中位数为67.2 vs. 23.9 AU/mL，P<0.001）以及ICAM-1水平更高。在这些患者中未发现可检测到的针对BNT162b2疫苗的IgE抗体。在4例过敏反应患者中，通过流式细胞术对辉瑞疫苗、1,2-二肉豆蔻酰-rac-甘油-3-甲氧基聚乙二醇（DMG-PEG）和PEG-2000进行的嗜碱性粒细胞激活试验均为阴性。BNT162b2疫苗接种后的急性超敏反应提示通过过敏毒素C5a的激活发生假过敏反应，且与IgE机制无关。疫苗反应者的抗BNT162b2 IgM水平显著更高，但其确切作用仍不清楚。
