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Allergic reactions to vaccines

John M Kelso, MD
Section Editor
N Franklin Adkinson, Jr, MD
Deputy Editor
Anna M Feldweg, MD


Severe allergic reactions to vaccines are rare and difficult to predict. An allergic reaction may be defined as an idiosyncratic reaction that is caused by an immunologic mechanism.

The World Allergy Organization (WAO) has recommended categorizing immunologic reactions to drugs (including vaccines) based upon the timing of the appearance of symptoms [1]. This system defines two general types of reactions: immediate and delayed. This approach is intended to distinguish immunoglobulin E (IgE)-mediated (type I immunologic reactions), which account for many immediate reactions, from other types, because these reactions carry the risk of life-threatening anaphylaxis if the patient is reexposed (table 1).

Immediate reactions begin within one hour of administration and may begin within minutes. IgE-mediated reactions are most likely to present within this time period.

Delayed reactions appear several hours to days after administration. These reactions may be caused by several different mechanisms, but they are rarely IgE-mediated.

This topic review focuses on immediate-type allergic reactions to vaccines, although delayed reactions are also discussed briefly. Of note, the administration of influenza vaccine to egg-allergic patients is discussed separately (see "Influenza vaccination in individuals with egg allergy"). Additional information about other types of adverse reactions to immunization, including unsubstantiated concerns about autism, is found in reviews of specific vaccines, elsewhere within UpToDate. (See "Autism spectrum disorder and chronic disease: No evidence for vaccines or thimerosal as a contributing factor".)

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Literature review current through: Sep 2017. | This topic last updated: Aug 04, 2017.
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  1. 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; 113:832.
  2. Sampson HA, Muñoz-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; 117:391.
  3. Bohlke K, Davis RL, Marcy SM, et al. Risk of anaphylaxis after vaccination of children and adolescents. Pediatrics 2003; 112:815.
  4. McNeil MM, Weintraub ES, Duffy J, et al. Risk of anaphylaxis after vaccination in children and adults. J Allergy Clin Immunol 2016; 137:868.
  5. Patja A, Mäkinen-Kiljunen S, Davidkin I, et al. Allergic reactions to measles-mumps-rubella vaccination. Pediatrics 2001; 107:E27.
  6. Cheng DR, Perrett KP, Choo S, et al. Pediatric anaphylactic adverse events following immunization in Victoria, Australia from 2007 to 2013. Vaccine 2015; 33:1602.
  7. National Center for Immunization and Respiratory Diseases. General recommendations on immunization --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2011; 60:1.
  8. Broder KR, Cortese MM, Iskander JK, et al. Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2006; 55:1.
  9. Kretsinger K, Broder KR, Cortese MM, et al. Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel. MMWR Recomm Rep 2006; 55:1.
  10. Talbot EA, Brown KH, Kirkland KB, et al. The safety of immunizing with tetanus-diphtheria-acellular pertussis vaccine (Tdap) less than 2 years following previous tetanus vaccination: Experience during a mass vaccination campaign of healthcare personnel during a respiratory illness outbreak. Vaccine 2010; 28:8001.
  11. Beytout J, Launay O, Guiso N, et al. Safety of Tdap-IPV given one month after Td-IPV booster in healthy young adults: a placebo-controlled trial. Hum Vaccin 2009; 5:315.
  12. Centers for Disease Control and Prevention (CDC). Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine from the Advisory Committee on Immunization Practices, 2010. MMWR Morb Mortal Wkly Rep 2011; 60:13.
  13. 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 2013; 172:171.
  14. Kang LW, Crawford N, Tang ML, et al. Hypersensitivity reactions to human papillomavirus vaccine in Australian schoolgirls: retrospective cohort study. BMJ 2008; 337:a2642.
  15. Kelso JM, Greenhawt MJ. Adverse reactions to vaccines in infectious diseases. In: Middleton's allergy: Principles and practice, 8th ed, Adkinson NF, Bochner BS, Burks AW, et al (Eds), Elsevier, Philadelphia 2014.
  16. Centers for Disease Control and Prevention (CDC). Syncope after vaccination--United States, January 2005-July 2007. MMWR Morb Mortal Wkly Rep 2008; 57:457.
  17. The Institute for Vaccine Safety. www.vaccinesafety.edu/components-Allergens.htm (Accessed on June 15, 2015).
  18. Vaccine excipient and media summary excipients included in United States vaccines, by vaccine. http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/B/latex-table.pdf (Accessed on June 15, 2015).
  19. Kelso JM, Jones RT, Yunginger JW. Anaphylaxis to measles, mumps, and rubella vaccine mediated by IgE to gelatin. J Allergy Clin Immunol 1993; 91:867.
  20. Sakaguchi M, Nakayama T, Inouye S. Food allergy to gelatin in children with systemic immediate-type reactions, including anaphylaxis, to vaccines. J Allergy Clin Immunol 1996; 98:1058.
  21. Sakaguchi M, Yamanaka T, Ikeda K, et al. IgE-mediated systemic reactions to gelatin included in the varicella vaccine. J Allergy Clin Immunol 1997; 99:263.
  22. Sakaguchi M, Miyazawa H, Inouye S. Specific IgE and IgG to gelatin in children with systemic cutaneous reactions to Japanese encephalitis vaccines. Allergy 2001; 56:536.
  23. Lasley MV. Anaphylaxis after booster influenza vaccine due to gelatin allergy. Pediatr Asthma Allergy Immunol 2007; 20:201.
  24. Stone CA Jr, Hemler JA, Commins SP, et al. Anaphylaxis after zoster vaccine: Implicating alpha-gal allergy as a possible mechanism. J Allergy Clin Immunol 2017; 139:1710.
  25. Kumagai T, Yamanaka T, Wataya Y, et al. A strong association between HLA-DR9 and gelatin allergy in the Japanese population. Vaccine 2001; 19:3273.
  26. Sakaguchi M, Nakayama T, Kaku H, et al. Analysis of HLA in children with gelatin allergy. Tissue Antigens 2002; 59:412.
  27. Kuno-Sakai H, Kimura M. Removal of gelatin from live vaccines and DTaP-an ultimate solution for vaccine-related gelatin allergy. Biologicals 2003; 31:245.
  28. O'Brien TC, Maloney CJ, Tauraso NM. Quantitation of residual host protein in chicken embryo-derived vaccines by radial immunodiffusion. Appl Microbiol 1971; 21:780.
  29. Kelso JM. Raw egg allergy-a potential issue in vaccine allergy. J Allergy Clin Immunol 2000; 106:990.
  30. 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; 128:215.
  31. Grabenstein JD. Clinical management of hypersensitivities to vaccine components. Hosp Pharm 1997; 32:77.
  32. Heidary N, Cohen DE. Hypersensitivity reactions to vaccine components. Dermatitis 2005; 16:115.
  33. Patrizi A, Rizzoli L, Vincenzi C, et al. Sensitization to thimerosal in atopic children. Contact Dermatitis 1999; 40:94.
  34. Lee-Wong M, Resnick D, Chong K. A generalized reaction to thimerosal from an influenza vaccine. Ann Allergy Asthma Immunol 2005; 94:90.
  35. Audicana MT, Muñoz D, del Pozo MD, et al. Allergic contact dermatitis from mercury antiseptics and derivatives: study protocol of tolerance to intramuscular injections of thimerosal. Am J Contact Dermat 2002; 13:3.
  36. Lear JT, English JS. Anaphylaxis after hepatitis B vaccination. Lancet 1995; 345:1249.
  37. 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; 23:664.
  38. Hamilton RG, Brown RH, Veltri MA, et al. Administering pharmaceuticals to latex-allergic patients from vials containing natural rubber latex closures. Am J Health Syst Pharm 2005; 62:1822.
  39. DiMiceli L, Pool V, Kelso JM, et al. Vaccination of yeast sensitive individuals: review of safety data in the US vaccine adverse event reporting system (VAERS). Vaccine 2006; 24:703.
  40. 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; 122:1233.
  41. Martín-Muñoz MF, Pereira MJ, Posadas S, et al. Anaphylactic reaction to diphtheria-tetanus vaccine in a child: specific IgE/IgG determinations and cross-reactivity studies. Vaccine 2002; 20:3409.
  42. Skov PS, Pelck I, Ebbesen F, Poulsen LK. Hypersensitivity to the diphtheria component in the Di-Te-Pol vaccine. A type I allergic reaction demonstrated by basophil histamine release. Pediatr Allergy Immunol 1997; 8:156.
  43. Bégin P, Vu MQ, Picard M, et al. Spontaneous resolution of diphtheria-tetanus vaccine hypersensitivity in a pediatric population. Allergy 2011; 66:1508.
  44. Adverse events associated with childhood vaccines: Evidence bearing on causality, Stratton KR, Howe CJ, Johnston RB (Eds), National Academy Press, Washington, DC 1994.
  45. Systemic adverse effects of hepatitis B vaccines are rare. Prescrire Int 2004; 13:218.
  46. Nelson MR, Oaks H, Smith LJ, et al. Anaphylaxis complicating routine childhood immunization: Hemophilus Influenza b conjugated vaccine. Pediatr Asthma Allergy Immunol 2000; 14:315.
  47. Brotherton JM, Gold MS, Kemp AS, et al. Anaphylaxis following quadrivalent human papillomavirus vaccination. CMAJ 2008; 179:525.
  48. Nagao M, Fujisawa T, Ihara T, Kino Y. Highly increased levels of IgE antibodies to vaccine components in children with influenza vaccine-associated anaphylaxis. J Allergy Clin Immunol 2016; 137:861.
  49. Takahashi H, Pool V, Tsai TF, Chen RT. Adverse events after Japanese encephalitis vaccination: review of post-marketing surveillance data from Japan and the United States. The VAERS Working Group. Vaccine 2000; 18:2963.
  50. James JM, Burks AW, Roberson PK, Sampson HA. Safe administration of the measles vaccine to children allergic to eggs. N Engl J Med 1995; 332:1262.
  51. Ball R, Braun MM, Mootrey GT, Vaccine Adverse Event Reporting System Working Group. Safety data on meningococcal polysaccharide vaccine from the Vaccine Adverse Event Reporting System. Clin Infect Dis 2001; 32:1273.
  52. Ponvert C, Ardelean-Jaby D, Colin-Gorski AM, et al. Anaphylaxis to the 23-valent pneumococcal vaccine in child: a case-control study based on immediate responses in skin tests and specific IgE determination. Vaccine 2001; 19:4588.
  53. Ponvert C, Scheinmann P, de Blic J. Anaphylaxis to the 23-valent pneumococcal vaccine: a second explored case by means of immediate-reading skin tests with pneumococcal vaccines. Vaccine 2010; 28:8256.
  54. Centers for Disease Control (CDC). Systemic allergic reactions following immunization with human diploid cell rabies vaccine. MMWR Morb Mortal Wkly Rep 1984; 33:185.
  55. Swanson MC, Rosanoff E, Gurwith M, et al. IgE and IgG antibodies to beta-propiolactone and human serum albumin associated with urticarial reactions to rabies vaccine. J Infect Dis 1987; 155:909.
  56. Carey AB, Meltzer EO. Diagnosis and "desensitization" in tetanus vaccine hypersensitivity. Ann Allergy 1992; 69:336.
  57. Mayorga C, Torres MJ, Corzo JL, et al. Immediate allergy to tetanus toxoid vaccine: determination of immunoglobulin E and immunoglobulin G antibodies to allergenic proteins. Ann Allergy Asthma Immunol 2003; 90:238.
  58. Slater JE, Rabin RL, Martin D. Comments on cow's milk allergy and diphtheria, tetanus, and pertussis vaccines. J Allergy Clin Immunol 2011; 128:434; author reply 435.
  59. Begier EM, Burwen DR, Haber P, et al. Postmarketing safety surveillance for typhoid fever vaccines from the Vaccine Adverse Event Reporting System, July 1990 through June 2002. Clin Infect Dis 2004; 38:771.
  60. Hoyt RE, Herip DS. Severe systemic reactions attributed to the acetone-inactivated parenteral typhoid vaccine. Mil Med 1996; 161:339.
  61. Wise RP, Salive ME, Braun MM, et al. Postlicensure safety surveillance for varicella vaccine. JAMA 2000; 284:1271.
  62. Kelso JM, Mootrey GT, Tsai TF. Anaphylaxis from yellow fever vaccine. J Allergy Clin Immunol 1999; 103:698.
  63. Tseng HF, Liu A, Sy L, et al. Safety of zoster vaccine in adults from a large managed-care cohort: a Vaccine Safety Datalink study. J Intern Med 2012; 271:510.
  64. Kelso JM, Greenhawt MJ, Li JT, et al. Adverse reactions to vaccines practice parameter 2012 update. J Allergy Clin Immunol 2012; 130:25.
  65. Mark A, Björkstén B, Granström M. Immunoglobulin E responses to diphtheria and tetanus toxoids after booster with aluminium-adsorbed and fluid DT-vaccines. Vaccine 1995; 13:669.
  66. Aalberse RC, van Ree R, Danneman A, Wahn U. IgE antibodies to tetanus toxoid in relation to atopy. Int Arch Allergy Immunol 1995; 107:169.
  67. Wood RA, Setse R, Halsey N, Clinical Immunization Safety Assessment (CISA) Network Hypersensitivity Working Group. Irritant skin test reactions to common vaccines. J Allergy Clin Immunol 2007; 120:478.
  68. Bierman CW, Shapiro GG, Pierson WE, et al. Safety of influenza vaccination in allergic children. J Infect Dis 1977; 136 Suppl:S652.
  69. Miller JR, Orgel HA, Meltzer EO. The safety of egg-containing vaccines for egg-allergic patients. J Allergy Clin Immunol 1983; 71:568.
  70. Kelso JM, Cockrell GE, Helm RM, Burks AW. Common allergens in avian meats. J Allergy Clin Immunol 1999; 104:202.