VACCINE ALLERGY. Samar Ojaimi. Infectious Diseases, Monash Health PhD graduate, Walter and Eliza Hall Institute

VACCINE ALLERGY Samar Ojaimi Infectious Diseases, Monash Health PhD graduate, Walter and Eliza Hall Institute Outline  Vaccine adverse reactions ...
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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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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

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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

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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   

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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