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8/2/2019 2.3.2 Vaccine Production
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5th Annual Advocacy Project:
ImmuneWiseSection on Medical Students, Residents, and
Fellowship Trainees
2009-2010
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What About Mercury?Vaccine Components and ManufacturingProcess
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Live viruses
Killed viruses
Purified viral proteins
Inactivated bacterial toxins
Bacterial polysaccharides
Preservatives (eg, thimerosal)
Adjuvants (eg, aluminum salts) Additives to stabilize live, attenuated viruses
Residual substances from manufacturing
processOffit PA and Jew RK. Addressing parents concerns: Do vaccines contain harmful
preservatives, adjuvants, additives, or residuals? Pediatrics. 2003; 112(6):1394-1401
Vaccine Components
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Required component of vaccines since 1930s
1916 Typhoid Vaccine contaminated withStaphylococcus aureusled to 4 deaths, 68 serious
systemic infections and 26 kids with local abscesses Many other reports of bacterial and fungal
contamination
3 were licensed in US
Thimerosal
Phenol
2-Phenoxyethanol
Preservatives
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Removed from all multi-dose vaccines by 2001 bythe FDA Modernization Act of 1997
Previously in DTaP, Hep B, Hib
For a total of 187.5 micrograms mercury by 6 months Thimerosal contains ethylmercury, which is
excreted faster than methylmercury
Agency 5% BodyWeight
50% BodyWeight
95% BodyWeight
EPA 65 89 106
ATSDR 194 266 319
FDA 259 354 425
Exposure limits of methylmercury in micrograms by 6 months of age by % Body Weight
Thimerosal
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Current thimerosal containing vaccines:
Influenza
Meningococcal
Japanese Encephalitis Pneumococcal polysaccharide (Pneumovax)
Diphtheria-Tetanus
Thimerosal
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Studies published to date have not shownthimerosal exposure to be harmful 2004: UK prospective cohort study of >14,000 infants showed no convincing evidence
that thimerosal has deleterious effect on neurological or psychological outcome (Heronand Golding)
2004: UK retrospective cohort study of 110,000 children found that with the exceptionof tics, there was no evidence that exposure to thimerosal through DTP/DT vaccinescauses neurodevelopmental disorders (Andrews et al.)
2007: CDC and Vaccine Data Safety Network published retrospective cohort study onneuropsychological outcomes in 1047 children aged 7-10 years old and found nodeleterious effects from early thimerosal exposure (Thompson et al.)
Vaccine Data Safety Network
Large case-control study of autism and thimerosal
exposure currently in data collecting phase
Thimerosal
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Enhance the immune response Enhance antigen uptake by antigen presenting cells
Activate antigen presenting cells
Induce production of cytokines and complement
Aluminum salts First added to diphtheria and tetanus in the 1930s
Benign Adverse Reactions mostly erythema
Aluminum quantities Breast milk 40 micrograms/liter
Formula 225 micrograms/liter
Vaccines 125 micrograms 625 micrograms/dose
Mouse studies established safety of aluminum in humans to
be
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AdjuvantsVaccines Containing Aluminum
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Stabilize vaccines from heat and cold
Prevent adherence to vials
Types of additives
Sugars (sucrose, lactose)
Amino acids (glycine, glutaminic acid) Proteins (gelatin, albumin)
Known adverse events
Immediate type hypersensitivity to gelatin
Additives
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Vaccine Trade Name Manufacturer
Dtap Tripedia Aventis Pasteur
Influenza Fluzone Aventis Pasteur
Measles Attenuvax Merck and Co
Mumps Mumpsvax Merck and Co
Rubella Meruvax II Merck and Co
Measles, rubella MRVAX II Merck and Co
Mumps, rubella Biavax II Merck and Co
MMR MMR II Merck and Co
Varicella Varivax Merck and Co
Rabies Rabavert Chiron
Japaneseencephalitis
JE-Vax Aventis Pasteur
Additives containing gelatin
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Albumin derived from human serum derivedfrom human blood
Theoretical risk of infection
FDA requirement that albumin derived from
screened donors
No viral diseases have ever been associatedwith the use of human albumin
Additives
albumin & infectious risks
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Vaccine Brand Name Manufacturer
Measles Attenuvax Merck and Co
Mumps Mumpsvax Merck and Co
Rubella Meruvax Merck and Co
MMR MMR II Merck and Co
Additives containing albumin
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Gelatin, glycerol, enzymes, serum, amino acidsare derived from cows
Creutzfeld-Jacob Disease Caused by prions
No association of CJD to blood products
Prions not found in cow hooves (used to make gelatin)
Epidemiologic evidence does not support vaccines asa cause for CJD in the UK
Additives containing bovineDerived products
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Formaldehyde
Influenza, Polio, Diphtheria, Tetanus
Human blood contains 10x more than any one vaccine
Natural intermediate in synthesis of amino acids,purine, and thymidine
Animal and human studies do not show increased riskfor malignancies after formaldehyde exposure
Beta-propriolactone Rabies
Glutaraldehyde
Acellular pertussis
manufacturing residuals-Inactivating agents
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Theoretical risk of immediate-typehypersensitivity to residual antibiotics (used toprevent contamination during manufacturing)
Antibiotics used: Neomycin, streptomycin,polymyxin B, chlortetracycline, amphotericin
Only neomycin is associated with immediate-typehypersensitivity but no cases documented at this time
Risk of delayed-type hypersensitivity but not acontraindication
manufacturing residuals-antibiotics
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Egg allergies occur in 5% children with atopy
Vaccines manufactured in chick embryos
Influenza contraindicated if egg allergy, follow strictprotocol if asthma and egg allergy
Yellow fever
Measles and mumpsverysmall quantity egg
allergy in not a contraindication
manufacturing residuals-Egg proteins
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Studies on ThimerosalHeron J and Golding J. Thimerosal exposure in infants and developmental
disorders: A prospective cohort study in the United Kingdom does notsupport a causal association. Pediatrics. 2004; 114(3):577-583
Andrews N et al. Thimerosal exposure in infants and developmental disorders:A retrospective cohort study in the United Kingdom does not support acausal association. Pediatrics. 2004; 114(3) 584-591
Thompson WW et al. Early thimerosal exposure and neuropsychologicaloutcomes at 7 to 10 years. NEJM. 2007; 357(13): 1281-1292.
Other ReadingsOffit PA and Jew RK. Addressing parents concerns: Do vaccines containharmful preservatives, adjuvants, additives, or residuals? Pediatrics.2003; 112(6):1394-1401
AAP Media Thimerosal Speaking Points
Sears RW. The Vaccine Book.
McCarthy, J. Louder Than Words.
references