VACCINE ALLERGY Samar Ojaimi Infectious Diseases, Monash Health PhD graduate, Walter and Eliza Hall Institute
Outline Vaccine
adverse reactions Two relevant scenarios
Hypersensitivity to vaccine Hypersensitivity to components Vaccine
specifics https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcR6qPhfuQQVQkYf2dl1lAfN_XD893okhykcY6GAZ2L-X_MDMou
Vaccine 1796,
Edward Jenner
13 yo boy with vaccinia virus
“Vaccine”
by Louis Pasteur Since then… http://www.humanosphere.org/science/201 0/08/how-smallpox-got-beat-why-it-matters/
Hepatitis B
Myths
• Chronic fatigue syndrome • Multiple sclerosis
DTPw
OPV
• Sudden infant death • Neurological damage
• AIDS
Immunisation
Hib
MMR
• Diabetes Mellitus
• Crohn’s • Autism
Adapted from André, Vaccine, 2003
Some truths Vaccine
Reaction
Frequency
All
Anaphylaxis
1:50,000 – 1,000,000
OPV
Paralytic polio
1:750,000 (first dose)
Measles
Thrombocytopenic purpura
1:22,300
Rotavirus
Intussusception
1:11,000
Mumps
Meningoencephalitis
1:10,000
André, Vaccine, 2003
Types of Adverse Events Induced by vaccination
e.g. haematomas, vagal reactions, contamination
Vaccine components
e.g. Insufficient detoxification of toxins, live vaccines, constituents (adjuvants, preservatives)
Host immune response
Local inflammatory reactions (esp. with adjuvants, TLR) Arthus reaction (esp. booster vaccines) Systemic (24-48hrs for killed, 14-21days for live vaccines) Allergic Autoimmune – molecular mimicry (e.g. ITP, GBS)
Unknown
(poorly understood)
e.g. Intussusception with Rhesus rotavirus vaccine
Mahajan et al. CDI, 2012;36:E315
Understanding Vaccine Allergy
Immune-mediated hypersensitivity reactions Type Common Name Pathogenesis
Example
I
Immediate-type
IgE, mast cells
Anaphylaxis, urticaria, asthma, rhinitis
II
Antibody-antigen binding
IgG or IgM
IIa – Immune cytopenias IIb – Grave’s
III
Soluble antigenantibody complexes
Ag-Ab complexes
Serum Sickness, vasculitis
IV
Delayed-type
T-cell
IVa – Th1 cells: contact dermatitis IVb – Th2 cell: persistent asthma IVc – SJS / TEN IVd – neutrophilic inflammation
Adapted from Uzzaman et al. Allergy Asthma Proc, 2012;33:S96; Legendre, 2013;58:1140
http://www.oralhealthgroup.com/issues/image.aspx?src=/daily_i mages/OH-20090201-018-screeningfrompa75393_MI0002.jpg&size=170
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https://encryptedtbn2.gstatic.com/images?q=tbn:ANd9GcSaIXv_CzSK8prrugdSoIUXawtRfV-Tybohule5WAoFTXAvmx5cXSFaIEd
Galli & Tsai, Nat Med, 2012;18:693
Galli & Tsai, Nat Med, 2012;18:693
Scenario 1 I had an allergic reaction to a vaccine once, can I have it again?
Scenario 1 History, timing very important Probable:
Immediate, IgE-mediated, 1 system, but > 4 hrs
Scenario 1 Skin testing with vaccine Same brand SPT – undiluted (unless severe reaction, 1:10 or 1:100) Intradermal at 1:100 Note, poor specificity
Skin testing for potential component allergens If negative, administer and watch for 30mins If positive,
Risk vs benefit analysis Prior doses, antibody status
Scenario 2 Can my child receive a vaccine when they are allergic to…?
In vaccines IgE-mediated reactions often due to additives or residual component Gelatin, egg proteins, latex, milk proteins* Anaphylaxis (0.65-1.53 per 1,000,000)
Fatalities rare
Type IV, Delayed-type hypersensitivity reactions E.g. to aluminium / thimerosal / neomycin / formaldehyde
Gelatin Stabiliser Most
No FDA approved extract for SPT Sugared gelatine (Jell-O) alternate
Testing
specific IgE
https://encrypted-tbn2.gstatic.com/images?q=tbn:ANd9GcQnsMSnKPfQCmVissvfmUQlTTYUSrxCnlxgVohax0Jbh2_O9_h
allergenic component in vaccines Either porcine or bovine, cross-reactive SPT vaccine containing gelatin
Kelso et al. Ann Allergy Asthma Immunol , 2013;110:397
https://encryptedtbn1.gstatic.com/images?q=tbn:ANd9GcQEFj0S2am_FhX4T2OXWV rqpDRBRKevN7KutpQoihFIBO6O6OzymQ
Egg Egg
allergy 2nd most frequent food allergy (1-2% children)
Ovalbumin Content
0.03-0.31ug/ml
Estimated
amount likely to trigger reaction in allergic patients 130μg
In
Aus, rabies (Rabipur, not HDCV), yellow fever and Q-fever vaccines
http://cdn.medindia.net/health-infographics/images/flu-vaccine-production.jpg
Egg and Influenza Safety predominantly tested for trivalent influenza vaccines
E.g. Fluarix® (GSK), Fluvax® (CSL), Vaxigrip® (Sanofi) Recombinant (US) Multiple studies Note variable doses every year
Not contraindicated
Skin testing not recommended
Low sensitivity and specificity in predicting reaction
Measles and mumps viruses also grown in eggs, negligible amounts
Skin Prick testing to vaccine not recommended
Split – 10%, 9-% Evidence to suggest split dose not necessary
ASCIA guidelines, 2010
Egg and Yellow Fever Higher degree of egg protein As for Q-fever vaccine Contraindicated in those with anaphylaxis to vaccine or components In those with reactions post ingestion or positive testing to egg skin test to vaccine If positive, graded dosing If negative, give and observe 30 minutes
Uncommonly used Oral polio vaccine
4 cases, all allergic to cow’s milk proteins Presence of α-La (whey protein) in OPV
Milk derivatives as preservatives
Toxoid-based vaccines (DTaP) – casein
Major milk allergen Very few cases, no recommendations
https://encryptedtbn0.gstatic.com/images?q=tbn:ANd9G cSu1IIOM3qjzbtfZk13O48S1nZZnTElDRbJJl Y93y0XxbRVC9Z9
Cow’s milk proteins
Latex In
packaging (e.g. syringe or vial)
No
reports of Type I hypersensitivity reactions
Recommendations:
Seek alternate packaging/vaccine Remove stopper If unavoidable, give and watch
Yeast
https://encryptedtbn3.gstatic.com/images?q=tbn:ANd9GcSRgjZH4TO aQeB5tw39PtUjoKb53Vx9gwnX-WC6KFqyK9oL8b7o
Baker’s or Brewer’s yeast (Saccharomyces cerevisiae) in hepatitis B and Gardasil Theoretical risk, no reports Skin testing Give, watch or graded
Take home message
Kelso et al. J Allergy Clin Immunol, 2012,130(1):25-43
Graded administration
Kelso et al. J Allergy Clin Immunol, 2012,130(1):25-43
References
André. Vaccinology: past achievements, present roadblocks and future promises. Vaccine. 2003;21:5935 Badiu et al. Hypersensitivity reaction to human papillomavirus vaccine due to polysorbate 80. BMJ, 2012 Eldred et al.. Vaccine components and constituents: responding to consumer concerns, Med J Aus. 2006;184(4):170. Greenhawt. Establishing the Safety of Influenza Vaccine in Egg-Allergic Individuals. Pediatr Ann. 2013;42:122 Kelso. Allergic reactions after immunization. Ann Allergy Asthma 2013;110(6):397–401. Kelso et al. Adverse reactions to vaccines practice parameter 2012 update. J Allergy Clin Immunol. 2012;130(1):25–43. Leventhal JS et al. Hypersensitivity Reactions to Vaccine Constituents. Dermatitis. 2012;23(3):102–9. Mahajan D, et al. Annual report: Surveillance of adverse events following immunisation in Australia, 2011. Commun Dis Intell Q Rep. 2012;36(4):E315–32. Micheletti F, et al. Vaccine allergy evaluation and management at the specialized Green Channel Consultation Clinic. Clin Exp Allergy. 2012 ;42(7):1088–96. Parisi, et al. Hypersensitivity reactions to the Sabin vaccine in children with cow's milk allergy. Clin Exp Allergy. 2013;43(2):249–54. Roches et al. Egg-allergic patients can be safely vaccinated against influenza. Journal of Allergy and Clinical Immunology. J Allergy Clin Immunol. 2012;130(5):1213–1216. Rutkowski K, Ewan PW, Nasser SM. Administration of Yellow Fever Vaccine in Patients with Egg Allergy. Int Arch Allergy Immunol. 2013;161(3):274–8. Siegrist CA. Mechanisms Underlying Adverse Reactions to Vaccines. J Comp Path. 2007;137:S46–S50. Woei Kang Liew et al. Anaphylaxis fatalities and admissions in Australia. Journal of Allergy and Clinical Immunology. J Allergy Clin Immunol. 2009;123(2):434–42. Wood RA. Allergic reactions to vaccines. Pediatr Allergy Immuno1. 2013;24(6):521–6. http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home (last accessed 10/11/2014) http://www.allergy.org.au/images/stories/pospapers/ascia_guidelines_influenza_vaccination_egg_allerg ic_individual_2010.pdf (last accessed 10/11/2014)
Thank You