Singapore Institute of Technology
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Anaphylatoxin Complement 5a in Pfizer BNT162b2-Induced Immediate-Type Vaccine Hypersensitivity Reactions.

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posted on 2023-05-29, 05:10 authored by Xin Rong Lim, Grace Yin Lai Chan, Justina Wei Lynn Tan, Carol Yee Leng Ng, Choon Guan Chua, Guat Bee Tan, Stephrene Seok Wei Chan, Kiat Hoe Ong, Ying Zhi Tan, Sarah Hui Zhen Tan, Claire Min Li Teo, Samuel Shang Ming Lee, Bernard Yu Hor Thong, Pui Lam Bernard LeungPui Lam Bernard Leung

Abstract: The underlying immunological mechanisms of immediate-type hypersensitivity reactions (HSR) to COVID-19 vaccines are poorly understood. We investigate the mechanisms of immediatetype 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, p < 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


This work is supported by the research fund of the Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital and a research grant from the National Centre for Infectious Diseases, Singapore, Catalyst Grant #FY2021LXR.


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This is the publisher's PDF version of: Lim, X.R.; Chan, G.Y.L.; Tan, J.W.L.; Ng, C.Y.L.; Chua, C.G.; Tan, G.B.; Chan, S.S.W.; Ong, K.H.; Tan, Y.Z.; Tan, S.H.Z.; Teo, C.M.L.; Lee, S.S.M.; Thong, B.Y.H.; Leung, B.P.L. Anaphylatoxin Complement 5a in Pfizer BNT162b2-Induced Immediate-Type Vaccine Hypersensitivity Reactions. Vaccines 2023, 11, 1020.

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Dr Lim Xin Rong;

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