{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T13:25:44Z","timestamp":1793453144756,"version":"4.5.0"},"reference-count":36,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T00:00:00Z","timestamp":1684800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital","award":["#FY2021LXR"],"award-info":[{"award-number":["#FY2021LXR"]}]},{"name":"National Centre for Infectious Diseases, Singapore","award":["#FY2021LXR"],"award-info":[{"award-number":["#FY2021LXR"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>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, p &lt; 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.<\/jats:p>","DOI":"10.3390\/vaccines11061020","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T10:51:56Z","timestamp":1684839116000},"page":"1020","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Anaphylatoxin Complement 5a in Pfizer BNT162b2-Induced Immediate-Type Vaccine Hypersensitivity Reactions"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1167-353X","authenticated-orcid":false,"given":"Xin Rong","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace Yin Lai","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justina Wei Lynn","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol Yee Leng","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choon Guan","family":"Chua","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guat Bee","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Haematology, Tan Tock Seng Hospital, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephrene Seok Wei","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Haematology, Tan Tock Seng Hospital, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiat Hoe","family":"Ong","sequence":"additional","affiliation":[{"name":"Department of Haematology, Tan Tock Seng Hospital, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying Zhi","family":"Tan","sequence":"additional","affiliation":[{"name":"Health and Social Sciences, Singapore Institute of Technology, Singapore 138683, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Hui Zhen","family":"Tan","sequence":"additional","affiliation":[{"name":"Health and Social Sciences, Singapore Institute of Technology, Singapore 138683, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire Min Li","family":"Teo","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel Shang Ming","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard Yu Hor","family":"Thong","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1119-4934","authenticated-orcid":false,"given":"Bernard Pui Lam","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore 308433, Singapore"},{"name":"Health and Social Sciences, Singapore Institute of Technology, Singapore 138683, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,23]]},"reference":[{"key":"ref_1","unstructured":"(2022, August 20). 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