Vaccination & Allergy · 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
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VACCINE
ALLERGYSamar 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
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Vaccine
1796, Edward Jenner
13 yo boy with vaccinia virus
“Vaccine” by Louis Pasteur
Since then…
Immunisation
Hepatitis B
• Chronic fatigue
syndrome
• Multiple sclerosis
DTPw
• Sudden infant death
• Neurological damage
MMR
• Crohn’s
• Autism
Hib
• Diabetes Mellitus
OPV
• AIDS
Myths
Adapted from André, Vaccine, 2003
Some truths
André, Vaccine, 2003
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
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 cytopeniasIIb – Grave’s
III Soluble antigen-
antibody
complexes
Ag-Ab
complexes
Serum Sickness, vasculitis
IV Delayed-type T-cell IVa – Th1 cells: contact dermatitisIVb – Th2 cell: persistent asthmaIVc – SJS / TENIVd – neutrophilic inflammation
Adapted from Uzzaman et al. Allergy Asthma Proc, 2012;33:S96; Legendre, 2013;58:1140
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Galli & Tsai, Nat Med, 2012;18:693
Scenario 1I had an allergic reaction to a vaccine once, can I
have it again?
Scenario 1
History, timing very important
Probable:
Immediate, IgE-mediated, <4 hrs post
With more than one of:
Dermatological, respiratory, cardiovascular and gastrointestinal manifestations
Possible
Signs/symptoms of only 1 of above, Or,
Signs/symptoms from >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 2Can 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 allergenic component in vaccines
Either porcine or bovine, cross-reactive
SPT vaccine containing gelatin
No FDA approved extract for SPT
Sugared gelatine (Jell-O) alternate
Testing specific IgE
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Kelso et al. Ann Allergy Asthma Immunol , 2013;110:397
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
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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
ASCIA guidelines, 2010
Skin Prick testing to
vaccine not recommended
Split – 10%, 9-%
Evidence to suggest split
dose not necessary
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
Cow’s milk proteins
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
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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
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Yeast
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
Re
fere
nc
es
André. Vaccinology: past achievements, present roadblocks and future promises. Vaccine. 2003;21:593-5
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 ExpAllergy. 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. IntArch 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
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