Safety of adjuvants and excipients in vaccines

Vaccines are named either for the antigen that they contain or the disease that they prevent, but they contain a number of excipients that serve to maintain proper pH, prevent microbial growth, act as stabilizers, or enhance the immune response to the vaccine. The objective of this article is to provide information for pharmacists who address patient concerns related to the safety of vaccine adjuvants and excipients and to offer suggestions and resources to address these issues in the community. Vaccine adjuvants improve the potency of vaccines, allowing for decreased doses of antigens or fewer doses in a vaccine series. Aluminum salts are the only vaccine adjuvant currently licensed in the United States and are included in vaccines such as Haemophilus influenzae type b, diphtheria–tetanus–acellular pertussis (DTaP), pneumococcal conjugate, hepatitis A, and hepatitis B. Aluminum adjuvants enhance phagocytosis of the vaccine antigen and inflammation that recruits immune cells.1 Aluminum is the most common metal found in nature. Aluminum can be neurotoxic and has been linked to dementia in patients with renal failure who receive large amounts of aluminum-containing antacids used as phosphate binders.2 This has led to the question of whether the amount of aluminum given to infants and children with the current vaccination schedule could lead to developmental delay or decreases in learning and memory. Patients can be assured that the amount of aluminum received during several vaccinations is well below the minimum risk level for daily intake. The aluminum exposure from vaccines in the first 6 months of life is about 4 mg. During this same time, the infant can be exposed to 10 mg aluminum in breast milk, about 40 mg in infant formula, or about 120 mg in soy-based formula. The aluminum exposure from a dose of vaccine is about 1,000 times less than the amount of aluminum from a dose of antacid.2 Aluminum has been used in vaccines for more than 75 years with hundreds of millions of doses given. Parents should be told that the aluminum can cause pain or redness around the injection site and in rare cases a harmless lump under the skin, but no long-term effects have been associated with aluminum in vaccines.3,4 Other compounds may be added to vaccines that are not adjuvants. For example, thimerosal is a preservative containing ethyl mercury that is no longer used as a preservative in childhood vaccines. It was reviewed in a previous installment of Vaccine Update.5 Formaldehyde is used during the manufacture of some vaccines to inactivate the pathogens. Although formaldehyde can cause cancerous changes to cells in vitro at certain doses, it does not have that property in either animals or humans. It is most widely known for its use as an embalming agent and as a component of cigarette smoke, which may alarm some patients. After manufacture and dilution, some vaccines (e.g. DTaP, hepatitis A, hepatitis B, polio) contain 0.1 mg formaldehyde or less per dose. This amount is 600 times less than has been given safely to animals and will not increase the patient’s risk for cancer or other ill effects.6 Some components of vaccines can elicit allergic responses ranging from mild to severe reactions, including anaphylaxis. Patients should be properly screened for all medication, food, and substance allergies using both openended questions and those that are vaccine specific. Latex can be found in some syringe plungers and in the rubber stoppers of some vaccine vials. For patients with a documented latex allergy, remove the rubber stopper of the vaccine or consider an alternate delivery technique to avoid adverse reactions. Latex content is described in prescribing information. Yellow fever and all influenza vaccine preparations are manufactured by using cellular components from chicken eggs that act as a viral growth medium during production. The final vaccine products contain measurable quantities of egg protein and should not be administered to any patient with a history of anaphylactic reaction to eggs. Influenza vaccine can be administered to individuals who can eat eggs.7 Gelatin is used in vaccines as a stabilizing agent and can be found in many commonly administered vaccines, including influenza (Fluzone brand), measles–mumps–rubella, varicella (Varivax), zoster (Zostavax), and DTaP (Tripedia brand). Gelatin has been estimated to cause immediate hypersensitivity reactions in approximately one person in every 2 million doses administered and is typically the responsible component when such reactions occur. Although immunizers can ask patients about allergies to food, the predictive value of this correlation is not very high.8 Another feature of vaccines that raises questions with patients is the presence of antibiotics. Many vaccines contain trace amounts of antibacterials such as neomycin, polymixin B, and streptomycin. These are used to prevent