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.

Allergy Asthma and Clinical Immunology Alfred Health Melbourne VIC Australia

Allergy Unit Malaga Regional University Hospital UMA ARADyAL Málaga Spain

Centre in Allergic Mechanisms of Asthma London UK

Departamento de CienciasMédicasBásicas Facultad de Medicina Instituto de Medicina Molecular Aplicada Universidad San Pablo CEU CEU Universities Madrid España

Department of Allergy Immunology and Respiratory Medicine Central Clinical School Monash University and Alfred Health Melbourne Vic Australia

Department of Biochemistry and Molecular Biology School of Chemistry Complutense University Madrid Spain

Department of Clinical Pharmacy and Pharmacology University Medical Center Groningen University of Groningen Groningen The Netherlands

Department of Dermatology and Allergy Center Odense Research Center for Anaphylaxis Odense University Hospital University of Southern Denmark Odense Denmark

Department of Environmental Medicine Medical Faculty University Augsburg Augsburg Germany

Department of Immunology and Pathology Monash University Melbourne VIC Australia

Department of Immunology University of Toronto Toronto ON Canada

Department of Infection and Immunity Luxembourg Institute of Health Esch sur Alzette Luxembourg

Department of Medicine and School of Microbiology APC Microbiome Ireland University College Cork Cork Ireland

Department of Medicine Division of Hospital Medicine Stanford University Stanford CA USA

Department of Medicine Division of Pulmonary and Critical Care Medicine Stanford University Stanford CA USA

Department of National Heart and Lung Institute Immunomodulation and Tolerance Group Allergy and Clinical Immunology Imperial College London London UK

Department of Otolaryngology Head and Neck Surgery Beijing TongRen Hospital Capital Medical University Beijing China

Department of Otolaryngology Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore

Department of Otorhinolaryngology Amsterdam University Medical Centers Amsterdam The Netherlands

Department of Otorhinolaryngology Head and Neck Surgery Section of Rhinology and Allergy University Hospital Marburg Philipps Universität Marburg Marburg Germany

Department of Paediatrics Allergy and Clinical Immunology Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore

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

Department of Respiratory Medicine 1st Faculty of Medicine Charles University and Thomayer Hospital Prague Czech Republic

Department of Respiratory Medicine and Allergology Institute for Clinical Science Skane University Hospital Lund University Lund Sweden

Departmentt of Microbiology Immunology and Transplantation KU Leuven Catholic University of Leuven Leuven Belgium

Division of Immunology and Allergy Food Allergy and Anaphylaxis Program The Hospital for Sick Children Toronto ON Canada

Division of Medical Biotechnology Department of Pathophysiology and Allergy Research Center for Pathophysiology Infectiology and Immunology Medical University of Vienna Vienna Austria

Institut de Recerca Sant Joan de Déu Barcelona Spain

Institute of Environmental Medicine Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany

Instituto de Salud Carlos 3 RETIC ARADYAL Madrid Spain

Office of Vaccines Research and Review Center for Biologics Evaluation and Research US Food and Drug Administration Silver Spring MD USA

Paul Ehrlich Institut Federal Institute for Vaccines and Biomedicines Langen Germany

School of Medicine University CEU San Pablo Madrid Spain

Sean N Parker Center for Allergy and Asthma Research at Stanford University Stanford CA USA

Swiss Institute of Allergy and Asthma Research University Zurich Zurich Switzerland

Translational Medicine Research Institute The Hospital for Sick Children Toronto ON Canada

Transylvania University Brasov Romania

Zobrazit více v PubMed

Pfizer and BioNTech achieve first authorization in the world for a vaccine to combat COVID‐19; 2020. https://www.pfizer.com/news/press‐release/press‐release‐detail/pfizer‐and‐biontech‐achieve‐first‐authorization‐world. Accessed January 14, 2021.

Pfizer . Pfizer and BioNTech celebrate historic first authorization in the U.S. of vaccine to prevent COVID‐19; 2020. https://www.pfizer.com/news/press‐release/press‐release‐detail/pfizer‐and‐biontech‐celebrate‐historic‐first‐authorization. Accessed January 13, 2021.

U.S. FDA Takes Additional Action in Fight Against COVID‐19 By Issuing Emergency Use Authorization for Second COVID‐19 Vaccine; 2020. https://www.fda.gov/news‐events/press‐announcements/fda‐takes‐additional‐action‐fight‐against‐covid‐19‐issuing‐emergency‐use‐authorization‐second‐covid. Accessed January 14, 2021.

Moderna . Press Release; 2021. https://investors.modernatx.com/news‐releases. Accessed January 22, 2021.

AstraZeneca’s COVID‐19 vaccine authorised for emergency supply in the UK; 2020. https://www.astrazeneca.com/media‐centre/press‐releases/2020/astrazenecas‐covid‐19‐vaccine‐authorised‐in‐uk.html. Accessed January 14, 2021.

van Riel D, de Wit E. Next‐generation vaccine platforms for COVID‐19. Nat Mater. 2020;19(8):810‐812. PubMed

World Health Organization . Draft landscape of COVID‐19 candidate vaccines; 2021. https://www.who.int/publications/m/item/draft‐landscape‐of‐covid‐19‐candidate‐vaccines. Accessed January 14, 2021.

Karamloo F, Konig R. SARS‐CoV‐2 immunogenicity at the crossroads. Allergy. 2020;75(7):1822‐1824. PubMed PMC

Klimek L, Jutel M, Akdis CA, et al. ARIA‐EAACI statement on severe allergic reactions to COVID‐19 vaccines ‐ an EAACI‐ARIA position paper. Allergy. 2020;76(6):1624‐1628. PubMed

Azkur AK, Akdis M, Azkur D, et al. Immune response to SARS‐CoV‐2 and mechanisms of immunopathological changes in COVID‐19. Allergy. 2020;75(7):1564‐1581. PubMed PMC

FDA US . CFR ‐ Code of Federal Regulations Title 21; 2010. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=312.32. Accessed January 22, 2021.

Morris L, Swofford S. Vaccine Safety. Prim Care. 2020;47(3):431‐441. PubMed

Siegrist CA. Mechanisms underlying adverse reactions to vaccines. J Comp Pathol. 2007;137(Suppl 1):S46‐50. PubMed

Spencer JP, Trondsen Pawlowski RH, Thomas S. Vaccine adverse events: separating myth from reality. Am Fam Physician. 2017;95(12):786‐794. PubMed

Kelso JM, Greenhawt MJ, Li JT, et al. Adverse reactions to vaccines practice parameter 2012 update. J Allergy Clin Immunol. 2012;130(1):25‐43. PubMed

Views TD‐CsHDNa . 653 Deaths +12,044 Other Injuries Reported Following COVID Vaccine, Latest CDC Data Show; 2021. https://childrenshealthdefense.org/defender/vaers‐injuries‐covid‐vaccine‐cdc‐data/. Accessed March 8, 2021.

U.S. Department for Health and Human Services . Common Terminology Criteria for Adverse Events (CTCAE). Version 5.0; 2017. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7. pdf. Accessed May 28, 2021.

Sampson HA, Munoz‐Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report–Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006;117(2):391‐397. PubMed

McNeil MM, DeStefano F. Vaccine‐associated hypersensitivity. J Allergy Clin Immunol. 2018;141(2):463‐472. PubMed PMC

Radice A, Carli G, Macchia D, Farsi A. Allergic reactions after vaccination: translating guidelines into clinical practice. Eur Ann Allergy Clin Immunol. 2019;51(2):51‐61. PubMed

Watts MM, Marie DA. Anaphylaxis. Allergy Asthma Proc. 2019;40(6):453‐456. PubMed

Bilo MB, Martini M, Tontini C, Corsi A, Antonicelli L. Anaphylaxis. Eur Ann Allergy Clin Immunol. 2021;53(1):4‐17. PubMed

Jensen F, Woudwyk M, Teles A, et al. Estradiol and progesterone regulate the migration of mast cells from the periphery to the uterus and induce their maturation and degranulation. PLoS One 2010;5(12):e14409. PubMed PMC

Johansson SG, Bieber T, Dahl R, et al. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol. 2004;113(5):832‐836. PubMed

National Advisory Committee on Immunization . Canadian Immunization Guide. Anaphylaxis and other acute reactions following vaccination 2020. https://www.canada.ca/en/public‐health/services/publications/healthy‐living/canadian‐immunization‐guide‐part‐2‐vaccine‐safety/page‐4‐early‐vaccine‐reactions‐including‐anaphylaxis.html. Accessed January 23, 2021.

Department for Health and Wellbeing, Government of South Australia . Vasovagal Episode or Anaphylaxis; 2019. https://www.sahealth.sa.gov.au/wps/wcm/connect/7bf436004f0c7c268dc7af791a12b24c/Vasovagal+episode+or+anaphylaxis+Chart+‐+201907+%28v1.0%29.pdf?MOD=AJPERES&CACHEID=ROOTWORKSPACE‐7bf436004f0c7c268dc7af791a12b24c‐niQpYNW. Accessed January 14, 2021.

Kochhar S, Salmon DA. Planning for COVID‐19 vaccines safety surveillance. Vaccine. 2020;38(40):6194‐6198. PubMed PMC

Ruggeberg JU, Gold MS, Bayas JM, et al. Anaphylaxis: case definition and guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. 2007;25(31):5675‐5684. PubMed

Wittes J, Crowe B, Chuang‐Stein C, et al. The FDA's Final Rule on Expedited Safety Reporting: Statistical Considerations. Stat Biopharm Res. 2015;7(3):174‐190. PubMed PMC

Minor PD. Live attenuated vaccines: Historical successes and current challenges. Virology. 2015;480:379‐392. PubMed

Stratton K, Ford A, Rusch E, Clayton EW, editors. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: National Academies Press; 2011. PubMed

Nilsson L, Brockow K, Alm J, et al. Vaccination and allergy: EAACI position paper, practical aspects. Pediatr Allergy Immunol. 2017;28(7):628‐640. PubMed

Su JR, Moro PL, Ng CS, Lewis PW, Said MA, Cano MV. Anaphylaxis after vaccination reported to the Vaccine Adverse Event Reporting System, 1990–2016. J Allergy Clin Immunol. 2019;143(4):1465‐1473. PubMed PMC

CDC . Vaccine Safety Datalink (VSD); 2020. https://www.CDC.gov/vaccinesafety/ensuringsafety/monitoring/vsd/index.html. Accessed January 23, 2021.

Bohlke K, Davis RL, Marcy SM, et al. Risk of anaphylaxis after vaccination of children and adolescents. Pediatrics 2003;112(4):815‐820. PubMed

McNeil MM, Weintraub ES, Duffy J, et al. Risk of anaphylaxis after vaccination in children and adults. J Allergy Clin Immunol. 2016;137(3):868‐878. PubMed PMC

Clark S, Wei W, Rudders SA, Camargo CA Jr. Risk factors for severe anaphylaxis in patients receiving anaphylaxis treatment in US emergency departments and hospitals. J Allergy Clin Immunol. 2014;134(5):1125‐1130. PubMed

Choe YJ, Lee H, Kim JH, Choi WS, Shin JY. Anaphylaxis following vaccination among children in Asia: A large‐linked database study. Allergy. 2021;76(4):1246‐1249. PubMed

Cheng DR, Perrett KP, Choo S, Danchin M, Buttery JP, Crawford NW. Pediatric anaphylactic adverse events following immunization in Victoria, Australia from 2007 to 2013. Vaccine. 2015;33(13):1602‐1607. PubMed

Dreskin SC, Halsey NA, Kelso JM, et al. International Consensus (ICON): allergic reactions to vaccines. World Allergy Organ J. 2016;9(1):32. PubMed PMC

Sarti L, Lezmi G, Mori F, Giovannini M, Caubet JC. Diagnosis and management of hypersensitivity reactions to vaccines. Expert Rev Clin Immunol. 2020;16(9):883‐896. PubMed

CDC . Recommendations of the Advisory Committee on Immunization Practices (ACIP): Use of Vaccines and Immune Globulins in Persons with Altered Immunocompetence; 1993. https://www.cdc.gov/mmwr/preview/mmwrhtml/00023141.htm. Accessed January 21, 2021. PubMed

CDC . Vaccine Excipient Summary: Excipients Included in U.S. Vaccines, by Vaccine; 2020. https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/b/excipient‐table‐2.pdf. Accessed January 14, 2021.

Echeverria‐Zudaire LA, Ortigosa‐del Castillo L, Alonso‐Lebrero E, et al. Consensus document on the approach to children with allergic reactions after vaccination or allergy to vaccine components. Allergol Immunopathol (Madr). 2015;43(3):304‐325. PubMed

World Health Organization . Draft landscape of COVID‐19 candidate vaccines; 2021. https://www.who.int/publications/m/item/draft‐landscape‐of‐covid‐19‐candidate‐vaccines. Accessed January 10, 2021.

Rodriguez‐Coira J, Sokolowska M. SARS‐CoV‐2 candidate vaccines ‐ composition, mechanisms of action and stages of clinical development. Allergy. 2021;76(6):1922‐1924. PubMed

Medicines and Healthcare products Regulatory Agency . Confirmation of guidance to vaccination centres on managing allergic reactions following COVID‐19 vaccination with the Pfizer/BioNTech vaccine; 2020. https://www.gov.uk/government/news/confirmation‐of‐guidance‐to‐vaccination‐centres‐on‐managing‐allergic‐reactions‐following‐covid‐19‐vaccination‐with‐the‐pfizer‐biontech‐vaccine. Accessed January 14, 2021.

CDC . Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Pfizer‐BioNTech COVID‐19 Vaccine — United States. December 14–23, 2020; 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7002e1.htm. Accessed January 14, 2021.

CDC . Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Moderna COVID‐19 Vaccine — United States. December 21, 2020–January 10, 2021; 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7004e1.htm. Accessed January 24, 2021. PubMed PMC

CDC . Interim Clinical Considerations for Use of mRNA COVID‐19 Vaccines Currently Authorized in the United States; 2021. https://www.cdc.gov/vaccines/covid‐19/info‐by‐product/clinical‐considerations.html#SARS‐CoV‐2‐infection. Accessed January 24, 2021.

CDC . Moderna COVID‐19 Vaccine Questions; 2021. https://www.cdc.gov/vaccines/covid‐19/info‐by‐product/moderna/moderna‐faqs.html. Accessed January 24, 2021.

Paul‐Ehrlich‐Institut . Corona vaccination in individuals suffereing from allergies; 2020. https://www.pei.de/EN/newsroom/positions/covid‐19‐vaccines/positions‐corona‐vaccination‐allergies.html. Accessed January 14, 2021.

Sokolowska M, Eiwegger T, Ollert M, et al. EAACI statement on the diagnosis, management and prevention of severe allergic reactions to COVID‐19 vaccines. Allergy. 2021. 10.1111/all.14739. Epub ahead of print. PubMed DOI PMC

Janeway CA, Travers P, Walport M, Shlomchik MJ. Immunobiology: The immune system in health and disease, 5th edn. New York, NY: Garland Publishing; 2001. Part V, The Immune System in Health and Disease. https://www.ncbi.nlm.nih.gov/books/NBK10775/

Dispenza MC. Classification of hypersensitivity reactions. Allergy Asthma Proc. 2019;40(6):470‐473. PubMed

Sampath V, Sindher SB, Alvarez Pinzon AM, Nadeau KC. Can food allergy be cured? What are the future prospects? Allergy. 2020;75(6):1316‐1326. PubMed

Kelos J. Allergic reactions to vaccines; 2021. https://www.uptodate.com/contents/allergic‐reactions‐to‐vaccines. Accessed January 14, 2021.

Pool V, Mege L, Abou‐Ali A. Arthus Reaction as an Adverse Event Following Tdap Vaccination. Vaccines (Basel) 2020;8(3):385. PubMed PMC

Marwa K . Type IV Hypersensitivity Reaction. In: Bayot ML, Abdelgawad I , editors. StatPearls [Internet]. StatPearls Publishing ; 2021. https://www.ncbi.nlm.nih.gov/books/NBK562228/

Chung EH. Vaccine allergies. Clin Exp Vaccine Res. 2014;3(1):50‐57. PubMed PMC

Zhang B, Li Q, Shi C, Zhang X. Drug‐Induced Pseudoallergy: A Review of the Causes and Mechanisms. Pharmacology. 2018;101(1–2):104‐110. PubMed

Kim YN, Kim JY, Kim JW, et al. The Hidden Culprit: A Case of Repeated Anaphylaxis to Cremophor. Allergy Asthma Immunol Res. 2016;8(2):174‐177. PubMed PMC

De Luca JF, Holmes NE, Trubiano JA. Adverse reactions to vancomycin and cross‐reactivity with other antibiotics. Curr Opin Allergy Clin Immunol. 2020;20(4):352‐361. PubMed

Oza NB, Ryan JW, Ryan US, Berryer P, Pena G. Pulmonary anaphylaxis and the kallikrein‐kinin system. Adv Exp Med Biol. 1979;120A:473‐486. PubMed

Thong BY. Nonsteroidal anti‐inflammatory drug hypersensitivity in the Asia‐Pacific. Asia Pac Allergy. 2018;8(4):e38. PubMed PMC

Navines‐Ferrer A, Serrano‐Candelas E, Lafuente A, Munoz‐Cano R, Martin M, Gastaminza G. MRGPRX2‐mediated mast cell response to drugs used in perioperative procedures and anaesthesia. Sci Rep. 2018;8(1):11628. PubMed PMC

Bonvini SJ, Birrell MA, Dubuis E, et al. Novel airway smooth muscle‐mast cell interactions and a role for the TRPV4‐ATP axis in non‐atopic asthma. Eur Respir J. 2020;56(1):1901458. PubMed PMC

Ali H. Emerging Roles for MAS‐Related G Protein‐Coupled Receptor‐X2 in Host Defense Peptide, Opioid, and Neuropeptide‐Mediated Inflammatory Reactions. Adv Immunol. 2017;136:123‐162. PubMed

McNeil BD, Pundir P, Meeker S, et al. Identification of a mast‐cell‐specific receptor crucial for pseudo‐allergic drug reactions. Nature. 2015;519(7542):237‐241. PubMed PMC

Tatemoto K, Nozaki Y, Tsuda R, et al. Immunoglobulin E‐independent activation of mast cell is mediated by Mrg receptors. Biochem Biophys Res Commun. 2006;349(4):1322‐1328. PubMed

CDC . Lab Tests to Collect Shortly After Severe Allergic Reaction/Anaphylaxis Following COVID‐19 Vaccination; 2020. https://www.cdc.gov/vaccines/covid‐19/clinical‐considerations/testing‐after‐allergic‐reaction.html#:~:text=Tryptase%20is%20released%20from%20mast,characterize%20the%20severe%20allergic%20reaction. Accessed January 24, 2021.

Sahiner UM, Yavuz ST, Buyuktiryaki B, et al. Serum basal tryptase may be a good marker for predicting the risk of anaphylaxis in children with food allergy. Allergy. 2014;69(2):265‐268. PubMed

Valent P, Akin C, Arock M, et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol. 2012;157(3):215‐225. PubMed PMC

Greiner G, Sprinzl B, Gorska A, et al. Hereditary alpha tryptasemia is a valid genetic biomarker for severe mediator‐related symptoms in mastocytosis. Blood. 2020;37:238‐247. PubMed PMC

Porebski G, Kwiecien K, Pawica M, Kwitniewski M. Mas‐Related G Protein‐Coupled Receptor‐X2 (MRGPRX2) in Drug Hypersensitivity Reactions. Front Immunol. 2018;9:3027. PubMed PMC

Supajatura V, Ushio H, Nakao A, et al. Differential responses of mast cell Toll‐like receptors 2 and 4 in allergy and innate immunity. J Clin Invest. 2002;109(10):1351‐1359. PubMed PMC

Urb M, Sheppard DC. The role of mast cells in the defence against pathogens. PLoS Pathog. 2012;8(4):e1002619. PubMed PMC

McCurdy JD, Lin TJ, Marshall JS. Toll‐like receptor 4‐mediated activation of murine mast cells. J Leukoc Biol. 2001;70(6):977‐984. PubMed

Kajiwara N, Sasaki T, Bradding P, et al. Activation of human mast cells through the platelet‐activating factor receptor. J Allergy Clin Immunol. 2010;125(5):1137‐1145. PubMed

Ferguson GT, Cole J, Aurivillius M, et al. Single‐use autoinjector functionality and reliability for at‐home administration of benralizumab for patients with severe asthma: GRECO trial results. J Asthma Allergy. 2019;12:363‐373. PubMed PMC

Ito T, Smrz D, Jung MY, et al. Stem cell factor programs the mast cell activation phenotype. J Immunol. 2012;188(11):5428‐5437. PubMed PMC

CDC . What’s in Vaccines?; 2019. cdc.gov/vaccines/vac‐gen/additives.htm. Accessed January 14, 2021.

CDC . Vaccine Recommendations and Guidelines of the ACIP; 2020. https://www.cdc.gov/vaccines/hcp/acip‐recs/general‐recs/adverse‐reactions. html. Accessed May 28, 2021.

CDC . Latex in Vaccine Packaging; 2020. https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/b/latex‐table.pdf. Accessed January 14, 2021.

Magista S, Albanesi M, Chaoul N, et al. Safety of measles, mumps, and rubella vaccine in egg allergy: in vivo and in vitro management. Clin Mol Allergy. 2020;18(1):21. PubMed PMC

Cerecedo Carballo I, Dieguez Pastor MC, Bartolome Zavala B, Sanchez Cano M, de la Hoz CB. Safety of measles‐mumps‐rubella vaccine (MMR) in patients allergic to eggs. Allergol Immunopathol (Madr). 2007;35(3):105‐109. PubMed

Upton JEM, Hummel DB, Kasprzak A, Atkinson AR. No systemic reactions to influenza vaccination in egg‐sensitized tertiary‐care pediatric patients. Allergy, Asthma & Clinical Immunology. 2012;8(1):2. PubMed PMC

Kang J‐H. Effectiveness and safety of seasonal influenza vaccination in children with underlying respiratory diseases and allergy. Korean J Pediatr. 2014;57(4):164. PubMed PMC

Sharma K, Perrett KP, Wood N. Yellow Fever Vaccination In EGG‐Allergic Children. Pediatr Infect Dis J. 2020;39(6):e76‐e78. PubMed

CDC . Flu Vaccine and People with Egg. Allergies. 2020; https://www.cdc.gov/flu/prevent/egg‐allergies.htm. Accessed January 14, 2021.

Grohskopf LA, Sokolow LZ, Broder KR, Walter EB, Bresee JS, Fry AM. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2017–18 Influenza Season. MMWR. Recommend Rep. 2017;66(2):1‐20. PubMed PMC

Kelso JM, Jones RT, Yunginger JW. Anaphylaxis to measles, mumps, and rubella vaccine mediated by IgE to gelatin. J Allergy Clin Immunol. 1993;91(4):867‐872. PubMed

Pool V, Braun MM, Kelso JM, et al. Prevalence of anti‐gelatin IgE antibodies in people with anaphylaxis after measles‐mumps rubella vaccine in the United States. Pediatrics 2002;110(6):e71. PubMed

Nakayama T, Aizawa C, Kuno‐Sakai H. A clinical analysis of gelatin allergy and determination of its causal relationship to the previous administration of gelatin‐containing acellular pertussis vaccine combined with diphtheria and tetanus toxoids. J Allergy Clin Immunol. 1999;103(2):321‐325. PubMed

Sakaguchi M, Inouye S. Systemic allergic reactions to gelatin included in vaccines as a stabilizer. Jpn J Infect Dis. 2000;53(5):189‐195. PubMed

Kumagai T, Kamada M, Igarashi C, et al. Gelatin‐specific cellular immune responses persist for more than 3 years after priming with gelatin containing DTaP vaccine. Clin Exp Allergy. 2002;32(10):1510‐1514. PubMed

Patja A, Makinen‐Kiljunen S, Davidkin I, Paunio M, Peltola H. Allergic Reactions to Measles‐Mumps‐Rubella Vaccination. Pediatrics. 2001;107(2):e27. PubMed

Swiontek K, Morisset M, Codreanu‐Morel F, et al. Drugs of porcine origin‐A risk for patients with alpha‐gal syndrome? J Allergy Clin Immunol Pract. 2019;7(5):1687‐1690. PubMed

Stone CA Jr, Commins SP, Choudhary S, et al. Anaphylaxis after vaccination in a pediatric patient: further implicating alpha‐gal allergy. J Allergy Clin Immunol Pract. 2019;7(1):322‐324. PubMed PMC

Kuno‐Sakai H, Kimura M. Removal of gelatin from live vaccines and DTaP‐an ultimate solution for vaccine‐related gelatin allergy. Biologicals. 2003;31(4):245‐249. PubMed

Kattan JD, Konstantinou GN, Cox AL, et al. Anaphylaxis to diphtheria, tetanus, and pertussis vaccines among children with cow's milk allergy. J Allergy Clin Immunol. 2011;128(1):215‐218. PubMed

Slater JE, Rabin RL, Martin D. Comments on cow's milk allergy and diphtheria, tetanus, and pertussis vaccines. J Allergy Clin Immunol. 2011;128(2):434; author reply 435. PubMed

Zanoni G, Puccetti A, Dolcino M, et al. Dextran‐specific IgG response in hypersensitivity reactions to measles‐mumps‐rubella vaccine. J Allergy Clin Immunol. 2008;122(6):1233‐1235. PubMed

Freitas DRC, Moura E, Araújo G, et al. Investigation of an outbreak of hypersensitivity‐type reactions during the 2004 national measles‐mumps‐rubella vaccination campaign in Brazil. Vaccine. 2013;31(6):950‐954. PubMed

DiMiceli L, Pool V, Kelso JM, Shadomy SV, Iskander J. Team VAERS. Vaccination of yeast sensitive individuals: review of safety data in the US vaccine adverse event reporting system (VAERS). Vaccine. 2006;24(6):703‐707. PubMed

Brotherton JML, Gold MS, Kemp AS, McIntyre PB, Burgess MA, Campbell‐Lloyd S. Anaphylaxis following quadrivalent human papillomavirus vaccination. Can Med Assoc J. 2008;179(6):525‐533. PubMed PMC

Kwittken PL, Rosen S, Sweinberg SK. MMR Vaccine and Neomycin Allergy. Arch Pediatr Adolesc Med. 1993;147(2):128. PubMed

Elliman D, Dhanraj B. Safe MMR vaccination despite neomycin allergy. Lancet. 1991;337(8737):365. PubMed

Huang S, Zhu Z, Cai L, et al. Analysis on the risks of severe adverse events in rabies post‐exposure prophylaxis and appropriate decision‐making procedure. Human Vacc Immunotherap. 2018;15(9):2121‐2125. PubMed PMC

Henao MP, Ghaffari G. Anaphylaxis to polymyxin B–trimethoprim eye drops. Ann Allergy Asthma Immunol. 2016;116(4):372. PubMed

Dréno B, Zuberbier T, Gelmetti C, Gontijo G, Marinovich M. Safety review of phenoxyethanol when used as a preservative in cosmetics. J Eur Acad Dermatol Venereol. 2019;33(S7):15‐24. PubMed

Smith D, Gomez R, Davenport J. Latex content in adult vaccines. Mil Med. 2020;185(3–4):354‐355. PubMed

Russell M, Pool V, Kelso JM, Tomazic‐Jezic VJ. Vaccination of persons allergic to latex: a review of safety data in the Vaccine Adverse Event Reporting System (VAERS). Vaccine. 2004;23(5):664‐667. PubMed

U.S. FDA . Thimerosal and Vaccines; 2018. https://www.fda.gov/vaccines‐blood‐biologics/safety‐availability‐biologics/thimerosal‐and‐vaccines. Accessed January 24, 2021.

Ball LK, Ball R, Pratt RD. An assessment of thimerosal use in childhood vaccines. Pediatrics. 2001;107(5):1147‐1154. PubMed

Jacob SE, Brod B, Crawford GH. Clinically relevant patch test reactions in children‐a United States based study. Pediatr Dermatol. 2008;25(5):520‐527. PubMed

Centers for Disease C . Systemic allergic reactions following immunization with human diploid cell rabies vaccine. MMWR Morb Mortal Wkly Rep. 1984;33(14):185‐187. PubMed

Huang DB, Wu JJ, Tyring SK. A review of licensed viral vaccines, some of their safety concerns, and the advances in the development of investigational viral vaccines. J Infect. 2004;49(3):179‐209. PubMed PMC

Swanson MC, Rosanoff E, Gurwith M, Deitch M, Schnurrenberger P, Reed CE. IgE and IgG antibodies to beta‐propiolactone and human serum albumin associated with urticarial reactions to rabies vaccine. J Infect Dis. 1987;155(5):909‐913. PubMed

Fishbein DB, Yenne KM, Dreesen DW, Teplis CF, Mehta N, Briggs DJ. Risk factors for systemic hypersensitivity reactions after booster vaccinations with human diploid cell rabies vaccine: a nationwide prospective study. Vaccine. 1993;11(14):1390‐1394. PubMed

Xia S, Zhang Y, Wang Y, et al. Safety and immunogenicity of an inactivated SARS‐CoV‐2 vaccine, BBIBP‐CorV: a randomised, double‐blind, placebo‐controlled, phase 1/2 trial. Lancet Infect Dis. 2021;21(1):39‐51. PubMed PMC

Zhang Y, Zeng G, Pan H, et al. Safety, tolerability, and immunogenicity of an inactivated SARS‐CoV‐2 vaccine in healthy adults aged 18–59 years: a randomised, double‐blind, placebo‐controlled, phase 1/2 clinical trial. Lancet Infect Dis. 2021;21(2):181‐192. PubMed PMC

Ring J. Exacerbation of eczema by formalin‐containing hepatitis B vaccine in formaldehyde‐allergic patient. Lancet. 1986;328(8505):522‐523. PubMed

Kuritzky LA, Pratt M. Systemic allergic contact dermatitis after formaldehyde‐containing influenza vaccination. J Cutaneous Med Surg. 2015;19(5):504‐506. PubMed

Moghaddam A, Olszewska W, Wang B, et al. A potential molecular mechanism for hypersensitivity caused by formalin‐inactivated vaccines. Nat Med. 2006;12(8):905‐907. PubMed

Peebles JRS, Sheller James R, Collins Robert D, Jarzecka K, Mitchell Daphne B, Graham BS. Respiratory Syncytial Virus (RSV)–Induced Airway Hyperresponsiveness in Allergically Sensitized Mice Is Inhibited by Live RSV and Exacerbated by Formalin‐Inactivated RSV. J Infect Dis. 2000;182(3):671‐677. PubMed

Lauren CT, Belsito DV, Morel KD, LaRussa P. Case report of subcutaneous nodules and sterile abscesses due to delayed type hypersensitivity to aluminum‐containing vaccines. Pediatrics. 2016;138(4):e20141690. PubMed

Kelly E, Leahy R, McDermott M, et al. Persistent pruritic subcutaneous nodules at injection sites and other delayed type hypersensitivity reactions to aluminium adsorbed vaccines in Irish children: A case series. Acta Paediatr. 2020;109(12):2692‐2693. PubMed

Gordon SC, Bartenstein DW, Tajmir SH, Song JS, Hawryluk EB. Delayed‐type hypersensitivity to vaccine aluminum adjuvant causing subcutaneous leg mass and urticaria in a child. Pediatr Dermatol. 2018;35(2):234‐236. PubMed

Salik E, Løvik I, Andersen K, Bygum A. Persistent Skin Reactions and Aluminium Hypersensitivity Induced by Childhood Vaccines. Acta Derm Venereol. 2016;96(7):967‐971. PubMed

Bergfors E, Trollfors B. Sixty‐four children with persistent itching nodules and contact allergy to aluminium after vaccination with aluminium‐adsorbed vaccines—prognosis and outcome after booster vaccination. Eur J Pediatr. 2012;172(2):171‐177. PubMed

Johnson‐Weaver BT, McRitchie S, Mercier KA, et al. Effect of endotoxin and alum adjuvant vaccine on peanut allergy. J Allergy Clin Immuno. 2018;141(2):791‐794. PubMed PMC

Montana M, Verhaeghe P, Ducros C, Terme T, Vanelle P, Rathelot P. Safety review: squalene and thimerosal in vaccines. Therapie. 2010;65(6):533‐541. PubMed

Lippi G, Targher G, Franchini M. Vaccination, squalene and anti‐squalene antibodies: facts or fiction? Eur J Intern Med. 2010;21(2):70‐73. PubMed

Shi S, Zhu H, Xia X, Liang Z, Ma X, Sun B. Vaccine adjuvants: Understanding the structure and mechanism of adjuvanticity. Vaccine. 2019;37(24):3167‐3178. PubMed

Meller S, Gerber PA, Kislat A, et al. Allergic sensitization to pegylated interferon‐alpha results in drug eruptions. Allergy. 2015;70(7):775‐783. PubMed

Castells MC, Phillips EJ. Maintaining Safety with SARS‐CoV‐2 Vaccines. N Engl J Med. 2021;384(7):643‐649. PubMed PMC

Cabanillas B, Akdis C, Novak N. Allergic reactions to the first COVID‐19 vaccine: a potential role of polyethylene glycol? Allergy. 2021;76(6):1617‐1618. PubMed

Pfaar O, Mahler V. Allergic reactions to COVID‐19 ‐vaccination ‐ unveiling the secret(s). Allergy. 2021;76(6):1617‐1618. PubMed PMC

Kozma GT, Shimizu T, Ishida T, Szebeni J. Anti‐PEG antibodies: Properties, formation, testing and role in adverse immune reactions to PEGylated nano‐biopharmaceuticals. Adv Drug Deliv Rev. 2020;155:163‐175. PubMed

Stone CA, Liu Y, Relling MV, et al. Immediate hypersensitivity to polyethylene glycols and polysorbates: more common than we have recognized. J Allergy Clinical Immunol Pract. 2019;7(5):1533‐1540. PubMed PMC

Povsic TJ, Lawrence MG, Lincoff AM, et al. Pre‐existing anti‐PEG antibodies are associated with severe immediate allergic reactions to pegnivacogin, a PEGylated aptamer. J Allergy Clin Immunol. 2016;138(6):1712‐1715. PubMed

Banerji A, Wickner PG, Saff R, et al. mRNA Vaccines to Prevent COVID‐19 Disease and Reported Allergic Reactions: Current Evidence and Suggested Approach. J Allergy Clin Immunol Pract. 2020;9(4):1423‐1437. PubMed PMC

Maggio E. Polysorbates, biotherapeutics and anaphylaxis: a review. Bioprocess Int. 2017;15(8). https://bioprocessintl.com/manufacturing/formulation/polysorbates-biotherapeutics‐and‐anaphylaxis‐a‐review/

Badiu I, Geuna M, Heffler E, Rolla G. Hypersensitivity reaction to human papillomavirus vaccine due to polysorbate 80. BMJ Case Rep. 2012;2012:bcr0220125797. PubMed PMC

Hong L, Wang Z, Wei X, Shi J, Li C. Antibodies against polyethylene glycol in human blood: A literature review. J Pharmacol Toxicol Methods. 2020;102:106678. PubMed

Nanomedicine and the COVID‐19 vaccines. Nat Nanotechnol. 2020;15(12):963. 10.1038/s41565-020-00820-0 PubMed DOI PMC

Jackson LA, Anderson EJ, Rouphael NG, et al. An mRNA Vaccine against SARS‐CoV‐2 ‐ Preliminary Report. N Engl J Med. 2020;383(20):1920‐1931. PubMed PMC

de Vrieze J. Pfizer's vaccine raises allergy concerns. Science. 2021;371(6524):10‐11. PubMed

Cabanillas B, Akdis C, Novak N. Allergic reactions to the first COVID-19 vaccine: a potential role of polyethylene glycol? Allergy. 2021;76(6):1621‐1623. PubMed

Garvey LH, Nasser S. Anaphylaxis to the first COVID‐19 vaccine: is polyethylene glycol (PEG) the culprit? Br J Anaesth. 2021;126(3):e106‐e108. PubMed PMC

Bruusgaard‐Mouritsen MA, Johansen JD, Garvey LH. Clinical manifestations and impact on daily life of allergy to polyethylene glycol (PEG) in ten patients. Clin Exp Allergy. 2021;51(3):463‐470. PubMed

Zhou ZH, Stone CA Jr, Jakubovic B, et al. Anti‐PEG IgE in anaphylaxis associated with polyethylene glycol. J Allergy Clin Immunol Pract. 2020;9(4):1731‐1733.e3. 10.1016/j.jaip.2020.11.011 PubMed DOI PMC

Klimek L, Jutel M, Akdis CA, et al. ARIA‐EAACI statement on severe allergic reactions to COVID‐19 vaccines – an EAACI‐ARIA position paper. Allergy. 2021;76(6):1624‐1628. PubMed

Hatziantoniou S, Maltezou HC, Tsakris A, Poland GA, Anastassopoulou C. Anaphylactic reactions to mRNA COVID‐19 vaccines: A call for further study. Vaccine. 2021;39(19):2605‐2607. PubMed PMC

Sokolowska M, Lukasik ZM, Agache I, et al. Immunology of COVID‐19: Mechanisms, clinical outcome, diagnostics, and perspectives‐A report of the European Academy of Allergy and Clinical Immunology (EAACI). Allergy. 2020;75(10):2445‐2476. PubMed PMC

European Medicines Agency . Annex I: Summary of product characteristics. https://www.ema.europa.eu/en/documents/product‐information/comirnaty‐epar‐product‐information_en.pdf. Accessed January 10, 2021.

Sasisekharan V, Pentakota N, Jayaraman A, Tharakaraman K, Wogan GN, Narayanasami U. Orthogonal immunoassays for IgG antibodies to SARS‐CoV‐2 antigens reveal that immune response lasts beyond 4 mo post illness onset. Proc Natl Acad Sci U S A. 2021;118(5):e2021615118. PubMed PMC

Hartley GE, Edwards ESJ, Aui PM, et al. Rapid generation of durable B cell memory to SARS‐CoV‐2 spike and nucleocapsid proteins in COVID‐19 and convalescence. Sci Immunol. 2020;5(54):eabf8891. PubMed PMC

Wajnberg A, Amanat F, Firpo A, et al. Robust neutralizing antibodies to SARS‐CoV‐2 infection persist for months. Science. 2020;370(6521):1227‐1230. PubMed PMC

Xie X, Zou J, Fontes‐Garfias CR, et al. Neutralization of N501Y mutant SARS‐CoV‐2 by BNT162b2 vaccine‐elicited sera. bioRxiv. 2001;2021(2021):2007.

Ashraf MU, Kim Y, Kumar S, Seo D, Ashraf M, Bae YS. COVID‐19 vaccines (revisited) and oral‐mucosal vector system as a potential vaccine platform. Vaccines (Basel). 2021;9(2):171. PubMed PMC

European Medicines Agency . Guideline on good pharmacovigilance practices (GVP). Product‐ or Population‐Specific Considerations I: Vaccines for prophylaxis against infectious diseases; 2012. https://www.ema.europa.eu/en/documents/scientific‐guideline/draft‐guideline‐good‐pharmacovigilance‐practices‐gvp‐product‐population‐specific‐considerations‐i_en.pdf. Accessed January 14, 2021.

Brotherton JM, Gold MS, Kemp AS, et al. Anaphylaxis following quadrivalent human papillomavirus vaccination. CMAJ. 2008;179(6):525‐533. PubMed PMC

Erlewyn‐Lajeunesse M, Hunt LP, Heath PT, Finn A. Anaphylaxis as an adverse event following immunisation in the UK and Ireland. Arch Dis Child. 2012;97(6):487‐490. PubMed

Zent O, Beran J, Jilg W, Mach T, Banzhoff A. Clinical evaluation of a polygeline‐free tick‐borne encephalitis vaccine for adolescents and adults. Vaccine. 2003;21(7–8):738‐741. PubMed

Ozaki T, Nishimura N, Muto T, et al. Safety and immunogenicity of gelatin‐free varicella vaccine in epidemiological and serological studies in Japan. Vaccine. 2005;23(10):1205‐1208. PubMed

Rouleau I, De Serres G, Drolet JP, et al. Increased risk of anaphylaxis following administration of 2009 AS03‐adjuvanted monovalent pandemic A/H1N1 (H1N1pdm09) vaccine. Vaccine. 2013;31(50):5989‐5996. PubMed

Kelso JM, Mootrey GT, Tsai TF. Anaphylaxis from yellow fever vaccine. J Allergy Clin Immunol. 1999;103(4):698‐701. PubMed

D'Souza RM, Campbell‐Lloyd S, Isaacs D, et al. Adverse events following immunisation associated with the 1998 Australian Measles Control Campaign. Commun Dis Intell. 2000;24(2):27‐33. PubMed

Kawai AT, Li L, Kulldorff M, et al. Absence of associations between influenza vaccines and increased risks of seizures, Guillain‐Barre syndrome, encephalitis, or anaphylaxis in the 2012–2013 season. Pharmacoepidemiol Drug Saf. 2014;23(5):548‐553. PubMed

Ropero‐Alvarez AM, Whittembury A, Bravo‐Alcantara P, Kurtis HJ, Danovaro‐Holliday MC, Velandia‐Gonzalez M. Events supposedly attributable to vaccination or immunization during pandemic influenza A (H1N1) vaccination campaigns in Latin America and the Caribbean. Vaccine. 2015;33(1):187‐192. PubMed

Halsey NA, Griffioen M, Dreskin SC, et al. Immediate hypersensitivity reactions following monovalent 2009 pandemic influenza A (H1N1) vaccines: reports to VAERS. Vaccine. 2013;31(51):6107‐6112. PubMed

Duclos P. Safety of immunisation and adverse events following vaccination against hepatitis B. Expert Opin Drug Saf. 2003;2(3):225‐231. PubMed

Li X, Ma SJ, Liu X, et al. Immunogenicity and safety of currently available Japanese encephalitis vaccines: a systematic review. Hum Vaccin Immunother. 2014;10(12):3579‐3593. PubMed PMC

Occurrence of adverse events following vaccination in patients with allergies: a prospective study