2.3.2 Vaccine Production

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

Documents

2.3.2 Vaccine Production