In addition to the designated antigen(s), a vaccine contains additives that may include adjuvants, preservatives, stabilizers, conjugating agents and antibiotics.
Adjuvants are designed to enhance the immune response to a vaccine antigen (immunogen) and to allow for use of smaller amounts of antigen. The most commonly used adjuvants in the United States are aluminum salts, such as aluminum hydroxide or aluminum phosphate. Originally, it was thought that aluminum salts acted as a repository for the vaccine antigen, but now it is believed that they also play a role in modulating the inflammatory response.
In the first six months of life, the total amount of aluminum contained in all routinely recommended vaccines is about 4 milligrams (mg). This is about one-half the amount of aluminum received from breast milk and less than one-tenth the amount of aluminum received from regular infant formula during the first six months of life. In over 70 years of use, aluminum salts have proven to be safe and effective.
In 2009, Cervarix (bivalent human papillomavirus vaccine) was licensed in the United States (although it is no longer available in this country). The vaccine contains a novel adjuvant system (AS04) known as monophosphoryl lipid A (a detoxified endotoxin) designed to enhance the immune response. The vaccine has been administered safely to hundreds of thousands of people.
Fluad was licensed by the Food and Drug Administration in November 2015 as the first seasonal influenza vaccine containing a novel adjuvant. Fluad is licensed for people 65 years of age or older but may become available for children. The vaccine contains MF59 as an adjuvant, consisting of an oil-in-water emulsion of squalene oil. Squalene occurs naturally in humans and is one of the major components of skin surface lipids.
Preservatives are added to vaccines to prevent the growth of bacteria or fungi that might cause contamination during use of a multi-dose vial. Four preservatives are currently used in some vaccines: thimerosal, 2-phenoxyethanol, phenol and benzethonium chloride. Some preservatives cannot be used with certain antigens. For example, thimerosal is not used in inactivated polio virus vaccine (IPV) as it may reduce the potency of certain poliovirus serotypes. Instead, 2-phenoxyethanol is used in IPV vaccine formulations.
Stabilizers protect a vaccine from degradation and temperature extremes during manufacture, shipping and storage. They consist of proteins (human serum albumin, gelatin), sugars (sucrose, lactose) or amino acids (glycine, glutamic acid). Because such small quantities of antigen are contained in a vaccine, stabilizers minimize adherence to glass in a vial or syringe. One H. influenzae type b vaccine contains only 10 mcg of polysaccharide antigen per dose. Live vaccines may contain only nanograms of antigen (103-105 viral particles per dose).
Protective immunity against encapsulated bacteria such as Neisseria meningitidis, S.pneumoniae and H. influenzae type b is induced by capsular polysaccharides. When used in inactivated vaccines, capsular polysaccharides are poorly immunogenic and do not result in long-term immunity. Conjugation of capsular polysaccharide to a protein carrier changes the nature of the immune response and converts the polysaccharide to a potent immunogen that can be used effectively in a vaccine. One disadvantage of conjugate vaccines is the complexity of the manufacturing process, resulting in high cost.
Types of proteins used as carriers include tetanus toxoid, diphtheria toxoid and CRM197(naturally occurring nontoxic diphtheria toxin). Recent reports suggest the protein carrier does not need to be directly linked to polysaccharide to enhance the immune response. Fixing the polysaccharide capsular antigen to a protein matrix may enhance a vaccine’s immunogenicity as effectively as a covalent bond (Thanawastien A, et al. Proc Natl Acad Sci USA. 2015;112:e1143-e1151). If proven to be effective, this would allow manufacture of conjugate vaccines in a less complicated process, reduce vaccine cost and enable wider use in developing countries.
Preservatives do not eliminate the risk of contamination, so antimicrobial agents may be added to a vaccine formulation. Antibiotics contained in licensed vaccines include streptomycin, polymyxin B, neomycin and gentamicin. Beta lactam antibiotics are not present in vaccines. Thus, a history of penicillin allergy is not an acceptable reason to avoid immunization.
Vaccines may contain tiny amounts of residual material that remains from the licensed manufacturing process, including yeast protein, formaldehyde and cellular DNA.
It is important to remember that despite their complexity, vaccines are remarkably safe and effective, and adverse reactions to vaccines are monitored constantly. The risk of anaphylaxis to any vaccine is estimated to be one case per 1 million to 2 million vaccine doses administered.
This article was written by H. Cody Meissner, M.d>, FAAP of APP News & Journals.