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

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

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

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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