Basophil activation test to BNT162b2 lacks specificity for predicting allergic reactions to the mRNA vaccine

Background: Allergic reactions to the coronavirus 2019 disease (COVID-19) mRNA vaccine (BNT162b2) were originally reported at higher rates than expected, contributing to vaccine hesitancy and, in some cases, unnecessary vaccine avoidance. Identification of a test that accurately predicts allergic re...

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Main Authors: Sydney Ann Kee, PhD, Ana Olivera, PhD, Lindsay Chatman, MSc, Muhammad B. Khalid, MD, Min Jenny Li, PhD, Eric Chu, MA, Ellen Zektser, BSN, MPH, Karen Laky, PhD, Pamela A. Frischmeyer-Guerrerio, MD, PhD
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Language:English
Published: Elsevier 2025-08-01
Series:Journal of Allergy and Clinical Immunology: Global
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Online Access:http://www.sciencedirect.com/science/article/pii/S2772829325000967
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author Sydney Ann Kee, PhD
Ana Olivera, PhD
Lindsay Chatman, MSc
Muhammad B. Khalid, MD
Min Jenny Li, PhD
Eric Chu, MA
Ellen Zektser, BSN, MPH
Karen Laky, PhD
Pamela A. Frischmeyer-Guerrerio, MD, PhD
author_facet Sydney Ann Kee, PhD
Ana Olivera, PhD
Lindsay Chatman, MSc
Muhammad B. Khalid, MD
Min Jenny Li, PhD
Eric Chu, MA
Ellen Zektser, BSN, MPH
Karen Laky, PhD
Pamela A. Frischmeyer-Guerrerio, MD, PhD
author_sort Sydney Ann Kee, PhD
collection DOAJ
description Background: Allergic reactions to the coronavirus 2019 disease (COVID-19) mRNA vaccine (BNT162b2) were originally reported at higher rates than expected, contributing to vaccine hesitancy and, in some cases, unnecessary vaccine avoidance. Identification of a test that accurately predicts allergic reactions to mRNA vaccines is critical to improve patient care, particularly given the growing use of mRNA-based technologies. Objective: We sought to determine the value of basophil activation tests (BATs) in predicting allergic reactions to the BNT162b2 vaccine. Methods: Blood from 16 participants enrolled in the clinical trial COVID Vaccine Allergy Reaction (COVAAR [ClinicalTrials.gov identifier NCT04977479]) who reported a systemic allergic reaction to their first dose of the COVID-19 mRNA vaccine was drawn before the second or booster dose and incubated with varying concentrations of the BNT162b2 vaccine or the vaccine component dimyristoyl glycerol–polyethylene glycol 2000. Basophil activation was quantified by CD63 expression via flow cytometry. In addition, 8 healthy volunteers (HVs) who tolerated the vaccine were included as controls. Results: Basophil responses to dimyristoyl glycerol–polyethylene glycol 2000 or the BNT162b2 vaccine were not higher among the COVAAR participants than among the HVs. Basophil responses did not correlate with time elapsed since last vaccine administration or previous COVID-19 infection. Instead, in both the HV and COVAAR groups, basophil reactivity was greater among those individuals who had received 2 or more vaccine doses than in those who had received only 1 dose. Conclusion: The BAT cannot predict allergic reactions to the BNT162b2 vaccine, and number of previous vaccinations received could be a confounding factor for interpreting the results of the BAT. Further studies are necessary to find a test that can accurately predict allergic reactions to the mRNA vaccine.
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spelling doaj-art-3bef645024424b4cb6266c9f359ca28d2025-08-20T03:42:40ZengElsevierJournal of Allergy and Clinical Immunology: Global2772-82932025-08-014310049510.1016/j.jacig.2025.100495Basophil activation test to BNT162b2 lacks specificity for predicting allergic reactions to the mRNA vaccineSydney Ann Kee, PhD0Ana Olivera, PhD1Lindsay Chatman, MSc2Muhammad B. Khalid, MD3Min Jenny Li, PhD4Eric Chu, MA5Ellen Zektser, BSN, MPH6Karen Laky, PhD7Pamela A. Frischmeyer-Guerrerio, MD, PhD8Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MdLaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MdLaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MdLaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MdLaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MdClinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MdLaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MdLaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MdLaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Md; Corresponding author: Pamela A. Frischmeyer-Guerrerio, MD, PhD, National Institute of Allergy and Infectious Diseases, 10 Center Dr, Bethesda, MD 20892-9806.Background: Allergic reactions to the coronavirus 2019 disease (COVID-19) mRNA vaccine (BNT162b2) were originally reported at higher rates than expected, contributing to vaccine hesitancy and, in some cases, unnecessary vaccine avoidance. Identification of a test that accurately predicts allergic reactions to mRNA vaccines is critical to improve patient care, particularly given the growing use of mRNA-based technologies. Objective: We sought to determine the value of basophil activation tests (BATs) in predicting allergic reactions to the BNT162b2 vaccine. Methods: Blood from 16 participants enrolled in the clinical trial COVID Vaccine Allergy Reaction (COVAAR [ClinicalTrials.gov identifier NCT04977479]) who reported a systemic allergic reaction to their first dose of the COVID-19 mRNA vaccine was drawn before the second or booster dose and incubated with varying concentrations of the BNT162b2 vaccine or the vaccine component dimyristoyl glycerol–polyethylene glycol 2000. Basophil activation was quantified by CD63 expression via flow cytometry. In addition, 8 healthy volunteers (HVs) who tolerated the vaccine were included as controls. Results: Basophil responses to dimyristoyl glycerol–polyethylene glycol 2000 or the BNT162b2 vaccine were not higher among the COVAAR participants than among the HVs. Basophil responses did not correlate with time elapsed since last vaccine administration or previous COVID-19 infection. Instead, in both the HV and COVAAR groups, basophil reactivity was greater among those individuals who had received 2 or more vaccine doses than in those who had received only 1 dose. Conclusion: The BAT cannot predict allergic reactions to the BNT162b2 vaccine, and number of previous vaccinations received could be a confounding factor for interpreting the results of the BAT. Further studies are necessary to find a test that can accurately predict allergic reactions to the mRNA vaccine.http://www.sciencedirect.com/science/article/pii/S2772829325000967Basophil activation testBATCOVID-19 mRNA vaccinevaccine reactionsvaccine allergypolyethylene glycol
spellingShingle Sydney Ann Kee, PhD
Ana Olivera, PhD
Lindsay Chatman, MSc
Muhammad B. Khalid, MD
Min Jenny Li, PhD
Eric Chu, MA
Ellen Zektser, BSN, MPH
Karen Laky, PhD
Pamela A. Frischmeyer-Guerrerio, MD, PhD
Basophil activation test to BNT162b2 lacks specificity for predicting allergic reactions to the mRNA vaccine
Journal of Allergy and Clinical Immunology: Global
Basophil activation test
BAT
COVID-19 mRNA vaccine
vaccine reactions
vaccine allergy
polyethylene glycol
title Basophil activation test to BNT162b2 lacks specificity for predicting allergic reactions to the mRNA vaccine
title_full Basophil activation test to BNT162b2 lacks specificity for predicting allergic reactions to the mRNA vaccine
title_fullStr Basophil activation test to BNT162b2 lacks specificity for predicting allergic reactions to the mRNA vaccine
title_full_unstemmed Basophil activation test to BNT162b2 lacks specificity for predicting allergic reactions to the mRNA vaccine
title_short Basophil activation test to BNT162b2 lacks specificity for predicting allergic reactions to the mRNA vaccine
title_sort basophil activation test to bnt162b2 lacks specificity for predicting allergic reactions to the mrna vaccine
topic Basophil activation test
BAT
COVID-19 mRNA vaccine
vaccine reactions
vaccine allergy
polyethylene glycol
url http://www.sciencedirect.com/science/article/pii/S2772829325000967
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