Physicians should be familiar with the major constituents of the products they use. The major constituents, including cell line derivation or animal derivatives, as relevant, are listed in the package inserts. If a vaccine is produced by different manufacturers, differences may exist in the active and/or inert ingredients and the relative amounts contained in the various products. The major constituents of vaccines include the following:

• Active immunizing antigens . Some vaccines consist of a single antigen that is a highly defined constituent (eg, tetanus or diphtheria toxoid). In other vaccines, antigens that provoke protective immune responses vary substantially in chemical composition and number (eg, acellular pertussis components, Haemophilus influenzae type b, and pneumococcal and meningococcal products). Vaccines containing live-attenuated viruses (eg, measles-mumps-rubella [MMR], measles-mumps-rubella-varicella [MMRV], varicella, oral poliovirus [OPV], live-attenuated influenza vaccine, oral rotavirus vaccine), killed viruses or portions of virus (eg, enhanced inactivated poliovirus [IPV], hepatitis A, and inactivated influenza vaccines), and viral proteins incorporated into a vaccine through recombinant technology (eg, hepatitis B vaccine, human papillomavirus [HPV] vaccine) produce both humoral and cellular-mediated responses to ensure long-term protection.


• Conjugating agents . Carrier proteins of proven immunologic potential (eg, tetanus toxoid, nontoxic variant of diphtheria toxin, meningococcal outer membrane protein complex), when chemically combined to less immunogenic polysaccharide antigens (eg, H influenzae type b, meningococcal and pneumococcal polysaccharides), enhance the type and magnitude of immune responses, particularly in people with immature immune systems, such as children younger than 2 years of age.


• Suspending fluid . The suspending fluid commonly is as simple as sterile water for injection or saline solution, but it may be a complex tissue-culture fluid. This fluid may contain proteins or other constituents derived from the medium and biological system in which the vaccine is produced (eg, egg antigens, gelatin, or cell culture-derived antigens).


• Preservatives, stabilizers, and antimicrobial agents . Some vaccines and immune globulin preparations contain added substances (eg, preservatives or stabilizers) or residual materials from the manufacturing process (eg, antibiotics or other chemicals, including trace amounts of thimerosal). Allergic reactions may occur if the recipient is sensitive to one or more of these additives. Whenever feasible, these reactions should be anticipated by screening the potential vaccinee for known severe allergy to specific vaccine components. Standardized forms are available to assist clinicians in screening for allergies and other potential contraindications to immunization (www.immunize.org/catg.d/p4060.pdf).


• Thimerosal . All routinely recommended vaccines for infants and children in the United States are available only as thimerosal-free formulations or contain only trace amounts of thimerosal, with the exception of some inactivated influenza vaccines. Inactivated influenza vaccine for pediatric use is available as a thimerosal preservative-containing formulation, a trace thimerosal-containing formulation, and a thimerosal-free formulation. Information about the thimerosal content of vaccines is available from the FDA (www.fda.gov/cber/vaccine/thimerosal.htm).
  
  The only nonvaccine biological agents that contain thimerosal in active production and distribution in the United States are certain antivenins. Immune Globulin Intravenous does not contain thimerosal or other preservatives, and none of the Rho (D) Immune Globulin (Human) products contain thimerosal (www.fda.gov/cber/blood/mercplasma.htm).


• Adjuvants . An aluminum salt commonly is used in varying amounts to increase immunogenicity and to prolong the stimulatory effect, particularly for vaccines containing inactivated microorganisms or their products (eg, hepatitis B and diphtheria and tetanus toxoids). New adjuvant technology permits use of molecules that stimulate innate immune responses to enhance immunogenicity of vaccine antigens and, thus, broaden the possibilities of vaccines to prevent diseases (eg, deacylated monophosphoryl lipid A plus aluminum hydroxide [ASO4], as used in one HPV vaccine) or spare the amount of antigen required when vast numbers of doses are needed (eg, pandemic influenza).