Review

. 2021 Jun;76(6):1640-1660.

doi: 10.1111/all.14840. Epub 2021 Jun 4.

Vaccines and allergic reactions: The past, the current COVID-19 pandemic, and future perspectives

Vanitha Sampath¹, Grace Rabinowitz¹, Mihir Shah¹, Surabhi Jain¹, Zuzana Diamant^{2

3

4

5}, Milos Jesenak⁶, Ronald Rabin⁷, Stefan Vieths⁸, Ioana Agache⁹, Mübeccel Akdis¹⁰, Domingo Barber^{11

12}, Heimo Breiteneder¹³, Sharon Chinthrajah^{1

14}, Tomas Chivato¹⁵, William Collins^{1

16}, Thomas Eiwegger^{17

18

19}, Katharine Fast¹, Wytske Fokkens²⁰, Robyn E O'Hehir²¹, Markus Ollert^{22

23}, Liam O'Mahony²⁴, Oscar Palomares²⁵, Oliver Pfaar²⁶, Carmen Riggioni^{27

28}, Mohamed H Shamji^{29

30}, Milena Sokolowska¹⁰, Maria Jose Torres³¹, Claudia Traidl-Hoffmann^{32

33}, Menno van Zelm^{34

35}, De Yun Wang³⁶, Luo Zhang³⁷, Cezmi A Akdis¹⁰, Kari C Nadeau^{1

14}

Affiliations

¹ Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford, CA, USA.
² Departmentt of Microbiology Immunology & Transplantation, KU Leuven, Catholic University of Leuven, Leuven, Belgium.
³ Department of Respiratory Medicine & Allergology, Institute for Clinical Science, Skane University Hospital, Lund University, Lund, Sweden.
⁴ Department of Clinical Pharmacy &Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁵ Department of Respiratory Medicine, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic.
⁶ Department of Pediatrics and Department of Clinical Immunology and Allergology, Jessenius Faculty of Medicine in Martin, Center for Vaccination in Special Situations, University Hospital in Martin, Comenius University in Bratislava, Bratislava, Slovakia.
⁷ Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
⁸ Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Langen, Germany.
⁹ Transylvania University, Brasov, Romania.
¹⁰ Swiss Institute of Allergy and Asthma Research (SIAF), University Zurich, Zurich, Switzerland.
¹¹ Departamento de CienciasMédicasBásicas, Facultad de Medicina, Instituto de Medicina Molecular Aplicada (IMMA), Universidad San Pablo-CEU, CEU Universities, Madrid, España.
¹² Instituto de Salud Carlos III, RETIC ARADYAL, Madrid, Spain.
¹³ Division of Medical Biotechnology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
¹⁴ Department of Medicine, Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, USA.
¹⁵ School of Medicine, University CEU San Pablo, Madrid, Spain.
¹⁶ Department of Medicine, Division of Hospital Medicine, Stanford University, Stanford, CA, USA.
¹⁷ Division of Immunology and Allergy, Food Allergy and Anaphylaxis Program, The Hospital for Sick Children, Toronto, ON, Canada.
¹⁸ Translational Medicine, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
¹⁹ Department of Immunology, University of Toronto, Toronto, ON, Canada.
²⁰ Department of Otorhinolaryngology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
²¹ Department of Allergy, Immunology and Respiratory Medicine, Central Clinical School, Monash University, and Alfred Health, Melbourne, Vic, Australia.
²² Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.
²³ Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis, Odense University Hospital, University of Southern Denmark, Odense, Denmark.
²⁴ Department of Medicine and School of Microbiology, APC Microbiome Ireland, University College Cork, Cork, Ireland.
²⁵ Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University, Madrid, Spain.
²⁶ Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Philipps-Universität Marburg, Marburg, Germany.
²⁷ Department of Paediatrics, Allergy and Clinical Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
²⁸ Institut de Recerca Sant Joan de Déu, Barcelona, Spain.
²⁹ Department of National Heart and Lung Institute, Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Imperial College London, London, UK.
³⁰ Centre in Allergic Mechanisms of Asthma, London, UK.
³¹ Allergy Unit, Malaga Regional University Hospital-UMA-ARADyAL, Málaga, Spain.
³² Department of Environmental Medicine, Medical Faculty, University Augsburg, Augsburg, Germany.
³³ Institute of Environmental Medicine, Helmholtz Zentrum München German Research Center for Environmental Health, Neuherberg, Germany.
³⁴ Department of Immunology and Pathology, Monash University, Melbourne, VIC, Australia.
³⁵ Allergy, Asthma and Clinical Immunology, Alfred Health, Melbourne, VIC, Australia.
³⁶ Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
³⁷ Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

PMID: 33811364
PMCID: PMC8251022
DOI: 10.1111/all.14840

Review

Vaccines and allergic reactions: The past, the current COVID-19 pandemic, and future perspectives

Vanitha Sampath et al. Allergy. 2021 Jun.

. 2021 Jun;76(6):1640-1660.

doi: 10.1111/all.14840. Epub 2021 Jun 4.

Authors

Affiliations

¹ Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford, CA, USA.
² Departmentt of Microbiology Immunology & Transplantation, KU Leuven, Catholic University of Leuven, Leuven, Belgium.
³ Department of Respiratory Medicine & Allergology, Institute for Clinical Science, Skane University Hospital, Lund University, Lund, Sweden.
⁴ Department of Clinical Pharmacy &Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁵ Department of Respiratory Medicine, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic.
⁶ Department of Pediatrics and Department of Clinical Immunology and Allergology, Jessenius Faculty of Medicine in Martin, Center for Vaccination in Special Situations, University Hospital in Martin, Comenius University in Bratislava, Bratislava, Slovakia.
⁷ Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
⁸ Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Langen, Germany.
⁹ Transylvania University, Brasov, Romania.
¹⁰ Swiss Institute of Allergy and Asthma Research (SIAF), University Zurich, Zurich, Switzerland.
¹¹ Departamento de CienciasMédicasBásicas, Facultad de Medicina, Instituto de Medicina Molecular Aplicada (IMMA), Universidad San Pablo-CEU, CEU Universities, Madrid, España.
¹² Instituto de Salud Carlos III, RETIC ARADYAL, Madrid, Spain.
¹³ Division of Medical Biotechnology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
¹⁴ Department of Medicine, Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, USA.
¹⁵ School of Medicine, University CEU San Pablo, Madrid, Spain.
¹⁶ Department of Medicine, Division of Hospital Medicine, Stanford University, Stanford, CA, USA.
¹⁷ Division of Immunology and Allergy, Food Allergy and Anaphylaxis Program, The Hospital for Sick Children, Toronto, ON, Canada.
¹⁸ Translational Medicine, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
¹⁹ Department of Immunology, University of Toronto, Toronto, ON, Canada.
²⁰ Department of Otorhinolaryngology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
²¹ Department of Allergy, Immunology and Respiratory Medicine, Central Clinical School, Monash University, and Alfred Health, Melbourne, Vic, Australia.
²² Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.
²³ Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis, Odense University Hospital, University of Southern Denmark, Odense, Denmark.
²⁴ Department of Medicine and School of Microbiology, APC Microbiome Ireland, University College Cork, Cork, Ireland.
²⁵ Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University, Madrid, Spain.
²⁶ Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Philipps-Universität Marburg, Marburg, Germany.
²⁷ Department of Paediatrics, Allergy and Clinical Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
²⁸ Institut de Recerca Sant Joan de Déu, Barcelona, Spain.
²⁹ Department of National Heart and Lung Institute, Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Imperial College London, London, UK.
³⁰ Centre in Allergic Mechanisms of Asthma, London, UK.
³¹ Allergy Unit, Malaga Regional University Hospital-UMA-ARADyAL, Málaga, Spain.
³² Department of Environmental Medicine, Medical Faculty, University Augsburg, Augsburg, Germany.
³³ Institute of Environmental Medicine, Helmholtz Zentrum München German Research Center for Environmental Health, Neuherberg, Germany.
³⁴ Department of Immunology and Pathology, Monash University, Melbourne, VIC, Australia.
³⁵ Allergy, Asthma and Clinical Immunology, Alfred Health, Melbourne, VIC, Australia.
³⁶ Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
³⁷ Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

PMID: 33811364
PMCID: PMC8251022
DOI: 10.1111/all.14840

Abstract

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.

Keywords: COVID-19; SARS-CoV-2; allergy; anaphylaxis; vaccine.

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Conflict of interest statement

Dr. Diamant reports personal fees from ALK, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, HAL Allergy, Merck Sharp & Dohme, and Sanofi‐Genzyme‐Regeneron and acted as Research Directorat QPS‐NL, an institution which received research support from several bio‐pharmaceutical companies, esp within respiratory: HAL Allergy, Foresee Pharmaceuticals, Patara Pharma (now Respivant), Novartis; Dr. Jesenak received honoraria, consultancy and speaker fees from Sanofi‐Pasteur, Pfizer, GlaxoSmithKline, Merck Sharp&Dohme, Takeda, ALK, Stallergenes‐Greer, Angelini, Novartis, Mundipharma and Berlin‐Chemie and acted as principal investigator in trials sponsored by BioCryst, Pharming, Octapharma, and Baxalta; Dr. Vieths reports personal fees from Swiss Society for Allergy and Immunology, SchattauerAllergologieHandbuch, Elsevier Nahrungsmittelallergien und Intoleranzen, and Karger Food Allergy: Molecular Basis and Clinical Practice and also reports non‐financial support from German Research Foundation, European Directorate for the Quality of Medicines and Health Care, European Academy of Allergy and Clinical Immunology, German Chemical Society (GDCh), AKM Allergiekongress, International Union of Immunological Societies, and from Spanish Society for Allergy and Clinical Immunology (SEAIC); Dr. Agache is an Associate Editor at Allergy and PAI; Dr. Chinthrajah reports grants from NIAID, CoFAR, Aimmune, DBV Technologies, Astellas, Regeneron, and FARE and is an advisory board member of Alladapt Therapeutics, Genentech, Novartis, and Sanofi; Dr. Eiwegger acts as local PI for company‐sponsored trials by DBV and sub‐investigator for Regeneron, holds grants from Innovation fund Denmark, CIHR. He is Co‐Investigator or scientific lead in three investigator‐initiated oral immunotherapy trials supported by the Food Allergy and Anaphylaxis Program SickKids and serves as associate editor for Allergy. He/his laboratory received unconditional/kind contributions from Macro Array Diagnostics and ALK. He holds advisory board roles for ALK; Dr. Barber reports grants from ALK, ALLERO therapeutics, personal fees from ALK and Aimmune; Dr. Ollert reports personal fees from Hycor Biomedical and is Scientific co‐founder of TolerogenicsSarL; Dr. Palomares received research grants from Inmunotek S.L., Novartis and MINECO, received fees for giving scientific lectures or participation in Advisory Boards from Allergy Therapeutics, Amgen, AstraZeneca, Diater, GlaxoSmithKline, S.A, Inmunotek S.L, Novartis, Sanofi‐Genzyme and Stallergenes; Dr. Pfaar reports grants and personal fees from ALK‐Abelló, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, BencardAllergie GmbH/Allergy Therapeutics, Lofarma, ASIT Biotech Tools S.A, Laboratorios LETI/LETI Pharma, Anergis S.A, and Glaxo Smith Kline, and grants from Biomay, Circassia, Pohl‐Boskamp, and Inmunotek S.L, and personal fees from MEDA Pharma/MYLAN, Mobile Chamber Experts (a GA2LEN Partner), Indoor Biotechnologies, Astellas Pharma Global, EUFOREA, ROXALL Medizin, Novartis, Sanofi‐Aventis and Sanofi‐Genzyme, Med Update Europe GmbH, streamedup! GmbH, John Wiley and Sons, AS, and Paul‐Martini‐Stiftung (PMS); Dr. Sokolowska reports grants from Swiss National Science Foundation (SNF) and from GSK; Dr. Torres reports grants from European Comission, SEAIC, and ISCIII and personal fees from Diater laboratory, Leti laboratory, and consultancy from Aimmune Therapeutics; Dr. Traidl‐Hoffmann reports personal fees from Sanofi Genzyme, Lilly Pharma, Novartis, Töpfer, and grants and personal fees from Sebapharma; Dr. van Zelm reports grants from NHMRC and has a patent pending, “Methods for detecting immune response”; Dr. Akdis reports grants from Allergopharma, Idorsia, Swiss National Science Foundation, Christine Kühne‐Center for Allergy Research and Education, European Commission's Horizon's 2020 Framework Programme, Cure, Novartis Research Institutes, Astra Zeneca, Scibase, advisory board from Sanofi/Regeneron, Glaxo Smith‐Kline, Scibase, and Novartis; Dr. Nadeau reports grants from National Institute of Allergy and Infectious Diseases (NIAID), National Heart, Lung, and Blood Institute (NHLBI), and National Institute of Environmental Health Sciences (NIEHS); Food Allergy Research & Education (FARE), Director of World Allergy Organization (WAO) Center of Excellence at Stanford; Advisor at Cour Pharma; Co‐founder of Before Brands, Alladapt, Latitude, and IgGenix; National Scientific Committee member at Immune Tolerance Network (ITN) and National Institutes of Health (NIH) clinical research centers; DSMB member for NHLBI, US patents for basophil testing, multifood immunotherapy and prevention, monoclonal antibody from plasmablasts, and device for diagnostics. All other authors report no COI.

Figures

**FIGURE 1**
Vaccination‐triggered anaphylaxis rates for major vaccines ¹⁹

**FIGURE 2**
Types of hypersensitivity reactions

**FIGURE 3**
Immunological (IgE‐mediated) and non‐immunological anaphylaxis

See this image and copyright information in PMC

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Vaccines and allergic reactions: The past, the current COVID-19 pandemic, and future perspectives

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Vaccines and allergic reactions: The past, the current COVID-19 pandemic, and future perspectives

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