Download Vaccine Production Presentation

5th Annual Advocacy Project:
ImmuneWise
Section on Medical Students,
Residents, and Fellowship Trainees
2009-2010
“What About Mercury?”
Vaccine Components and Manufacturing
Process
Vaccine Components
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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
process
Offit PA and Jew RK. Addressing parents’ concerns: Do vaccines contain harmful
preservatives, adjuvants, additives, or residuals? Pediatrics. 2003; 112(6):1394-1401
Preservatives
• Required component of vaccines since 1930s
– 1916 Typhoid Vaccine contaminated with
Staphylococcus aureus led 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
Thimerosal
• Removed from all multi-dose vaccines by 2001 by
the 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
Exposure limits of methylmercury in micrograms by 6 months of age by % Body Weight
Agency
5% Body
Weight
50% Body
Weight
95% Body
Weight
EPA
65
89
106
ATSDR
194
266
319
FDA
259
354
425
Thimerosal
• Current thimerosal containing vaccines:
– Influenza
– Meningococcal
– Japanese Encephalitis
– Pneumococcal polysaccharide (Pneumovax)
– Diphtheria-Tetanus
Thimerosal
• Studies published to date have not shown
thimerosal 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 (Heron
and Golding)
– 2004: UK retrospective cohort study of 110,000 children found that with the exception
of tics, there was no evidence that exposure to thimerosal through DTP/DT vaccines
causes neurodevelopmental disorders (Andrews et al.)
– 2007: CDC and Vaccine Data Safety Network published retrospective cohort study on
neuropsychological outcomes in 1047 children aged 7-10 years old and found no
deleterious 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
Adjuvants
• 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 <62 mg/kg/day
Adjuvants –
Vaccines Containing Aluminum
Additives
• 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 – containing gelatin
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
Japanese
encephalitis
JE-Vax
Aventis Pasteur
Additives –
albumin & infectious risks
• Albumin derived from human serum derived
from human blood
• Theoretical risk of infection
• FDA requirement that albumin derived from
screened donors
• No viral diseases have ever been associated
with the use of human albumin
Additives – containing albumin
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 bovine
Derived products
• Gelatin, glycerol, enzymes, serum, amino acids
are 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 as
a cause for CJD in the UK
manufacturing residualsInactivating agents
• 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 risk
for malignancies after formaldehyde exposure
• Beta-propriolactone
– Rabies
• Glutaraldehyde
– Acellular pertussis
manufacturing residualsantibiotics
• Theoretical risk of immediate-type
hypersensitivity to residual antibiotics (used to
prevent contamination during manufacturing)
• Antibiotics used: Neomycin, streptomycin,
polymyxin B, chlortetracycline, amphotericin
– Only neomycin is associated with immediate-type
hypersensitivity but no cases documented at this time
– Risk of delayed-type hypersensitivity but not a
contraindication
manufacturing residualsEgg proteins
• Egg allergies occur in 5% children with atopy
• Vaccines manufactured in chick embryos
– Influenza – contraindicated if egg allergy, follow strict
protocol if asthma and egg allergy
– Yellow fever
– Measles and mumps – very small quantity – egg
allergy in not a contraindication
references
Studies on Thimerosal
Heron J and Golding J. Thimerosal exposure in infants and developmental
disorders: A prospective cohort study in the United Kingdom does not
support 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 a
causal association. Pediatrics. 2004; 114(3) 584-591
Thompson WW et al. Early thimerosal exposure and neuropsychological
outcomes at 7 to 10 years. NEJM. 2007; 357(13): 1281-1292.
Other Readings
Offit PA and Jew RK. Addressing parents’ concerns: Do vaccines contain
harmful 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.