5th Annual Advocacy Project: ImmuneWise Section on Medical Students, Residents, and Fellowship Trainees

“What About Mercury?” Vaccine Components and Manufacturing Process

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): Vaccine Components

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 Preservatives

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 micrograms mercury by 6 months Thimerosal contains ethylmercury, which is excreted faster than methylmercury Agency5% Body Weight 50% Body Weight 95% Body Weight EPA ATSDR FDA Exposure limits of methylmercury in micrograms by 6 months of age by % Body Weight 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 Thimerosal

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

Adjuvants – Vaccines Containing Aluminum

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

VaccineTrade NameManufacturer DtapTripediaAventis Pasteur InfluenzaFluzoneAventis Pasteur MeaslesAttenuvaxMerck and Co MumpsMumpsvaxMerck and Co RubellaMeruvax IIMerck and Co Measles, rubellaMRVAX IIMerck and Co Mumps, rubellaBiavax IIMerck and Co MMRMMR IIMerck and Co VaricellaVarivaxMerck and Co RabiesRabavertChiron Japanese encephalitis JE-VaxAventis Pasteur Additives – containing gelatin

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 – albumin & infectious risks

VaccineBrand NameManufacturer MeaslesAttenuvaxMerck and Co MumpsMumpsvaxMerck and Co RubellaMeruvaxMerck and Co MMRMMR IIMerck and Co Additives – containing albumin

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 Additives – containing bovine Derived products

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 residuals- Inactivating agents

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 residuals- antibiotics

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 manufacturing residuals- Egg proteins

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): 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) Thompson WW et al. Early thimerosal exposure and neuropsychological outcomes at 7 to 10 years. NEJM. 2007; 357(13): Other Readings Offit PA and Jew RK. Addressing parents’ concerns: Do vaccines contain harmful preservatives, adjuvants, additives, or residuals? Pediatrics. 2003; 112(6): AAP Media – Thimerosal Speaking Points Sears RW. The Vaccine Book. McCarthy, J. Louder Than Words. references