lecture of 54 slide

1. Vaccine Allergy
BY
DR. Magdy Shafik
Senior Pediatric Consultant
Diploma, M.S ,Ph.D of Pediatric

2. .
Outline
• •Vaccine allergy (IgE mediated vs Non-IgE
mediated)
• Reactions to specific vaccines
• Vaccination Recommended

3. Introduction
• Vaccination is necessary (children receive 10
vaccines to protect against 16 disease)
• Protective effect extends to nonvaccinated
persons (herd immunity)
• Vaccine – associated hypersensitivity (IgE-
mediated or IgG, complement-mediated
anaphylactic, serious delayed-onset T cell
mediated systemic reaction) extremely rare
• Risk of anaphylaxis 1.31(95%Cl, 0.90-1.84)
per million vaccine dose

4. Type of vaccine components

5. Reactions
• IgE–Mediated Reactions to Vaccines
• IgE–Mediated Reactions to Vaccine
Constituents
• Non-IgE-Mediated Reactions to vaccine
Constituents
• Reactions to specific vaccines

7. Type of vaccine components
IgE Mediated

8. Incident of Anaphylaxis

9. Influenza vaccine

10. Immunoglobulin E-mediated reactions to
vaccine constituents other than the immunizing
agent
• Gelatin
• Egg
• Latex
• Yeast
• Milk

11. Gelatin
• A vaccine stabilizer of bovine or porcine origin
• Japan report anaphylaxis reaction after MMR
vaccination
• Anaphylaxis to some brands of MMR and
varicella vaccines, and also earlier in Japanese
encephalitis and influenza vaccines
• Japan and Germany removed gelatin or changed
to a less allergenic gelatin
• A new Japanese encephalitis vaccine does not
contain gelatin
• IgE for gelatin and skin test before give
vaccination

12. Gelatin with Alpha-gal allergy
• Alpha-gal sensitivity presents with delayed
anaphylaxis(3-6 hours) after consumption of red meat
with lesser degrees of reactivity to milk and gelatin
• 202 reported events 14 cases of adverse reactions to
zoster vaccine anaphylaxis
• Five (36%) of 14 cases of anaphylaxis had a known
associated beef, pork, gelatin, or alpha-gal allergy
• Both MMR and Zoster vaccine use bovine calf serum
during their production
• Global interest as the immunologic mechanism for
delayed anaphylaxis after ingestion of mammalian meat

14. Risk for reactions to gelatin-containing
vaccines
• Gelatin used in vaccines is of either bovine
or porcine origin (cross reaction)
• Some patients sensitized to beef or pork
meat are also sensitized to beef or pork
gelatin, which might place them at risk
for reactions to gelatin-containing vaccines
• • Strong association gelatin allergy and
human leukocyte antigen (HLA)-DR9 an
HLA type unique to Asians, suggesting a
genetic susceptibility to gelatin allergy

15. Egg

16. Egg with MMR
• Report in 1983 described two egg-allergic
children who suffered allergic reactions to
measles vaccine
• • Measles and mumps vaccines are grown in
chick embryo fibroblast culture
• • Measles or MMR vaccine was administered in
the normal manner to egg-allergic children
without adverse reaction
• • Recommendations that MMR vaccine can be
given routinely to children with egg allergy
without previous skin testing

17. Egg protein with influenza vaccine
• Safely to even severely egg-allergic recipients
• • Very low amount of egg protein (ovalbumin)
contained vaccine
• • History of only hives after egg ingestion can receive
TIV
• History of more severe reactions after egg ingestion
should be referred to an allergist to receive TIV
• • LAIV, the lowest amount of ovalbumin per dose, has
not been formally studied for safety in egg-allergic
individuals
• • LAIV also is contraindicated in any individual with
asthma
• • Skin testing (prick, intradermal) with the influenza
vaccine is not recommend

19. • Patients with egg allergy of any
severity should receive annual
influenza vaccinations
• • TIV, rather than the live
attenuated influenza vaccine(LAIV),
should be used for recipients with
egg allergy
• • All influenza vaccines available in
the United States contain low
amounts of ovalbumin

20. (Egg allergy with Influenza vaccine)

22. Egg with yellow fever
• Yellow fever vaccine is cultured in chicken
embryos and contains egg protein
• Anaphylactic reactions in egg-allergic persons
have been reported
• Chicken proteins other than those found in
chicken egg may be present in yellow fever
vaccine.
• A history of allergy after the ingestion of egg,
raw or cooked, should be sought before the
administration of yellow fever vaccine

23. Latex
• Vial stoppers and syringe plungers contain dry
natural rubber
• 167,223 reports in the VAERS database
through 2003 revealed 28 reports of
immediate-type allergic reactions to various
vaccines in Patients
• History of latex-precipitated anaphylaxis can
safely receive vaccines from vials with
nonlatex stoppers
• Risk of allergic reactions possibly due to latex
contamination of vaccines appears to be very
small

24. Latex in vaccine packing

25. Latex in vaccine packing

26. Yeast (Residual media)
• Hepatitis B vaccines are grown in Saccharomyces
cerevisiae (baker’s yeast or brewer’s yeast)
• Adverse reactions 15 case in 180,895 reports (rare)
• Quadrivalent human papillomavirus vaccine
(HPV4)contain residual yeast protein
• If history of immediate-type allergy to baker’s yeast and a
positive skin test response to S. cerevisiae, an
appropriate precaution is skin testing with
yeastcontaining vaccines before administration

27. Milk
• Described 8 children anaphylaxis within 1
hour of receiving DTaP or Tdap
• Anaphylactic reactions to DTaP or Tdap
vaccines are rare
• Patients with cow’s milk allergy tolerate
them without reaction
• Recommended that all patients and with
milk allergy, continue to receive these
vaccines on schedule

28. Recommended skin test

29. Skin test with Gelatin

30. Skin prick test

32. Reactions
• IgE–Mediated Reactions to Vaccines
• IgE–Mediated Reactions to Vaccine
Constituents
•
Non-IgE-Mediated Reactions to vaccine
Constituents
• Reactions to specific vaccines

33. Non-IgE Mediated Reactions to vaccine
• Minor, self-limited side effects
• Local (injection site) reactions such as pain,
warmth, tenderness, swelling, and erythema
• Mild systemic reactions such as fever
• No contraindications to further doses of any
vaccine
• Constituents (Neomycin, Thimerosal,
Aluminum) – delayed type hypersensitivity

34. Antimicrobials
• Gentamycin, tetracycline, neomycin,
streptomycin and polymyxin B are used
during the production to prevent bacterial
or fungal growth.
• Removed during the purification process
• Neomycin is contained in several
vaccines.
• Delayed-type hypersensitivity contact
dermatitis to neomycin

35. Preservations
• Thimerosal, 2-phenoxyethanol, and phenol
are used in multidose vials of vaccines to
prevent bacterial growth.
• MP rash to thimerosal in an influenza
vaccine (case report).
• Immediate-type reaction that may have
been caused by thimerosal in a vaccine
(case report)

36. • Removed thimerosal in vaccines used in
young children cause mercury toxicity
(neurologic disorders).
• Local or delayed-onset hypersensitivity to
thimerosal is not a contraindication to
vaccines.

37. Adjuvants
• Adjuvants are incorporated in to enhance or
direct the immune response of the vaccinated.
• Aluminum hydroxide and aluminum phosphate
are the most common adjuvants used in
vaccines
• No immediate hypersensitivity reactions
• Small granulomas or nodules with persistent
urticaria at the site can occur after aluminum-
containing vaccine

38. Management of patients with suspected
hypersensitivity to a vaccine

40. Pre-immunization testing and immunization

41. Graded doses

42. Reactions
• IgE–Mediated Reactions to Vaccines
• IgE–Mediated Reactions to Vaccine
Constituents
•
Non-IgE-Mediated Reactions to vaccine
Constituents
• Reactions to specific vaccines

43. REACTIONS TO SPECIFIC VACCINES
• Diphtheria vaccine: Local reaction >
generalized reaction.
• Hemophilus influenzae type b (Hib)
vaccine : Generalized urticaria after
vaccine by conjugate protein CRM 197(a
mutant diphtheria protein ).
• HBV :Relationship between HBV and
anaphylaxis in yeast sensitive individuals
(1:600,000)

44. • Human Papillomavirus Vaccine:
Anaphylaxis from 1 per 1 million76 to 2.6
per 100,000 doses.
• Influenza vaccine: VAERS reports from
1990 to 2005, during which 747 million
doses revealed 4 reports of death
occurring shortly after influenza
vaccination.
• JE vaccine : most affected patients have
anti-gelatin IgE, new vaccine does not
contain gelatin

45. • MMR: no relationship has been found
between anaphylactic reactions to MMR
vaccine and egg allergy.
:15% late onset of fever 5-12 days ,
increased risk of febrile seizure in
children, thrombocytopenia 1 in
1,000,000.
• Rabies vaccine : Two of the reported
patients had anaphylaxis to both
PCEC(purified chicken embryo cell) and
HDCV(Human diploid cell virus cell),
suggesting contains gelatin

46. • Varicella : Anaphylaxis 1 to 3 per 1 million
doses and gelatin allergy as the cause of
some of these reactions, 4% varicella like
lesion at the injection site, safety in
children with atopic dermatitis.
• Yellow fever : Anaphylaxis 7 per 1 million
doses and associated egg allergy
• : Encephalitis, infant < 9 months of age
• : YEL-AVD (vaccine-associated
viscerotrophic disease)

47. • Pertussis : Febrile seizure
• Polio : paralytic poliomyelitis in year 2000
after OPV(8-9 vaccine). In US, OPV
discontinued, favor of IPV.
• Tetanus : injected site reaction, Arthurs
reaction.
• Rotavirus: intussusception in infants by
oral rotavirus in 1998, now new live oral
rotavirus no increased risk
• .

48. Long-Term Consequences of Vaccination
• Atopy - infant vaccines do not increase the
risk of allergic disease.
• Autism - case series 12 children related MMR
• Autism - Many studies no association
between MMR and autism.
• Autoimmune - Guillain-Barré syndrome,
multiple sclerosis, DM type I, optic neuritis,
and transverse myelitis, has been reported.
• Autoimmune - evidence is inadequate to
accept or reject a causal relationship

49. Immunoglobulin preparations interfere live
viral vaccines

53. Conclusion
• Determine the culprit allergen ( Vaccine Vs
Constituents)
• Determine Immunoglobulin E or Non-
Immunoglobulin E
• Skin tests with the suspect vaccine and skin
tests or serum-specifc IgE antibody tests to
vaccine constituents (gelatin, egg, latex, or
yeast)