Canadian Immunization Guide
Seventh Edition - 2006

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Part 1
General Guidelines

• What's in a vaccine?
• Table 1. Type and Contents of Vaccines Currently Approved for Use in Canada

General Considerations

The goal of those concerned with immunization is the elimination of vaccine-preventable diseases. Eradication of smallpox has been achieved. Currently, global efforts are directed at the eradication of polio and the elimination of measles. Ongoing immunization programs with high vaccine coverage are needed to maintain low levels of other vaccine-preventable diseases. When the incidence of a communicable disease decreases to low levels because of successful vaccination programs, there is a potential for people to question the need to continue the programs, and this may lead to lower vaccine coverage and, inevitably, resurgence of the disease. Therefore, immunization providers must advocate for the continuation of successful programs.

An ideal vaccine would confer lifelong protection against a disease after a single dose. It would be inexpensive, stable during shipping and storage, easy to administer and without adverse effects. Researchers and vaccine manufacturers continue to work to improve vaccines; in the meantime, our existing vaccines save lives. The diseases against which vaccines protect may also change over time for reasons unrelated to vaccine programs. These factors mean that the efficacy, effectiveness and safety of vaccines and vaccination programs must be evaluated continually to ensure that Canadians achieve the greatest possible benefit.

In this Guide, information is presented on the immunizing agents available in Canada and their use in the prevention of communicable diseases. Recommendations on routine immunizations are discussed in some detail, and an attempt is made to answer most of the day-to-day queries from providers regarding immunization.

Because of variation in manufacturers' products, precise details of the dosage and route of administration of individual products are not usually given. Readers are referred to manufacturers' labelling and package inserts for this information. As well, the manufacturer has sought approval of the vaccine and provided evidence as to its safety and efficacy only when it is used in accordance with the product monograph. Some information in the Guide may differ from that in product monograph(s) and package inserts. Information in the Guide is based upon the best and most current publicly available scientific knowledge.

What's in a vaccine?

Vaccines are highly regulated, complex biologic products designed to induce a protective immune response both effectively and safely. The main vaccine types as well as the derivation, purpose and potential risk of vaccine constituents are summarized below. See Table 1 for specific information on the type and key constituents of each vaccine marketed in Canada.

Immunogen: The part of the vaccine that stimulates an immune response is also the basis for classification of vaccine type, as follows:

• Live attenuated: The vaccine contains whole, living bacteria or viruses that induce immunity by actively replicating within the host. Since the agent replicates within the recipient, the stimulus more closely resembles that associated with natural infection, resulting in longer lasting and broader immunity than can be achieved with other vaccine types. Attenuated means the vaccine strains are weakened so that infection is usually inapparent or very mild, in marked contrast to the natural infection (see inside back cover). Live vaccines require careful storage and handling to avoid inadvertent inactivation and are contraindicated for pregnant women and people with immunodeficiencies.

  Inactivated: The vaccine contains killed bacteria or virus. Such vaccines pose no risk for immunocompromised persons and may induce a broad immunity since multiple antigens are present. Disadvantages include the usual need for multiple doses because the response may be weaker than that induced by live organisms and potential toxicity associated with unwanted portions of the killed organism (as was true for the whole-cell pertussis vaccine).

  Subunit: The vaccine contains purified products that usually come from the bacteria or virus that causes natural infection but may also be synthesized in the laboratory using recombinant technology (e.g., hepatitis B surface antigen). These products may require inactivation to prevent toxic side effects, and all are purified through a variety of steps in the manufacturing process. The end products include proteins, polysaccharides and protein-polysaccharide conjugates. Subunit vaccines have excellent safety profiles and facilitate the preparation of a variety of combination products. Disadvantages include lower immunogenicity, which sometimes requires the presence of an adjuvant and/or multiple doses.

Adjuvant: A substance added to a vaccine to enhance the immune response by degree and/or duration, making it possible to reduce the amount of immunogen per dose or the total number of doses needed to achieve immunity. The only adjuvants used in vaccines currently marketed in Canada are aluminum salts (aluminum hydroxide, aluminum phosphate or potassium aluminum sulfate), which primarily enhance the immune response to proteins. They have been shown to be safe over seven decades of use. Rarely, they may cause injection site reactions, including subcutaneous nodules, granulomatous inflammation or contact hypersensitivity. Subcutaneous rather than intramuscular deposition, as occurs when using too short a needle, may increase the risk of such reactions. After oxygen and silicon, aluminum is the third most abundant element in the environment and daily exposure occurs, primarily through food. Infant formula contains from 0.2 to 1.1 mg aluminum/litre whereas vaccines contain from 0.2 to 0.85 mg per dose. Both exposures are considered to be within the limits of safety (see Keith et al. for a more detailed discussion).

Preservatives: Chemicals (e.g., thimerosal, phenol, 2 phenoxyethanol) added to multidose, killed or subunit vaccines in order to prevent serious secondary infections as a result of bacterial or fungal contamination. In recent years there has been a great deal of opposition to the use of thimerosal, an ethyl mercury derivative, because of a theoretical risk of brain damage. Scientific evidence has refuted this risk, and it is no longer necessary for health care providers to raise this as a concern before administering influenza or hepatitis B vaccines, which may contain thimerosal. Thimerosal-free versions of both vaccines are available for use in select circumstances (see the relevant chapters in this Guide ).

Additives: Substances other than those already mentioned may be added to vaccines for two different purposes:

• to support the growth and purification of specific immunogens and/or the inactivation of toxins. These include antibiotics added to prevent contamination during viral cell culture; substances needed for the growth of viruses, such as egg or yeast proteins, glycerol, serum, amino acids and enzymes; and formaldehyde used to inactivate viruses and protein toxins. Most of these reagents are removed in subsequent manufacturing steps, but minute "trace" amounts may remain in the final product. The amounts present are only of consequence for individuals who are allergic to them (see Table 1 for a listing of potential allergens in vaccines authorized for marketing in Canada). Concern has been expressed about formaldehyde because of its use as an embalming agent. However formaldehyde is also an intermediate in human metabolism, and the amount normally found in blood, even of a young infant, exceeds by 10 fold or more what is found in a dose of vaccine.
• to confirm product quality or stability. Compounds may be added to vaccines for a variety of manufacture-related issues: controlling acidity (pH); stabilizing immunogens through necessary steps in the manufacturing process, such as freeze drying; and preventing immunogens from adhering to the sides of glass vials with a resultant loss in immunogenicity. Examples of such additives include potassium or sodium salts, lactose, polysorbate 20 or 80, human serum albumin and a variety of animal proteins, such as gelatin and bovine serum albumin. Concerns have been expressed regarding the following:
  
  
  • Human serum albumin: There is a theoretical risk of infectious agents being present in products made from human blood. However, steps in the manufacturing process of both human albumin and vaccines that contain it greatly reduce the possibility of transmission of these agents. To date, there have been no documented cases of transmission of infectious agents by human serum albumin.
  • Gelatin: This protein may be the cause of rare hypersensitivity reactions to gelatin-containing vaccines (approximately 1 event per 2 million doses). Table 1 identifies which of the vaccines currently marketed in Canada contain gelatin. All individuals who have had an anaphylactic reaction to one of these products should be referred to an allergist, as should individuals with a history of immediate allergic reactions to foods containing gelatin.
  • Bovine reagents: The risk of transmitting variant Creutzfeld Jakob disease from vaccines containing bovine-derived material is theoretical, estimated to be 1 in 40 billion or less (see http://www.fda.gov/cber/BSE/risk.htm). In Canada, the bovine-derived reagents commonly added to vaccines included in the routine schedule are manufactured from animals considered to be free of bovine spongiform encephalopathy.
    

Table 1. Type and Contents of Vaccines Currently Approved for Use in Canada (May 2006)

Selected references

Keith LS, Jones DE, Chou C. Aluminum toxicokinetics regarding infant diet and vaccinations. Vaccine 2002;20:S13-17.

Offit PA, Jew RK. Addressing parents' concerns: Do vaccines contain harmful preservatives, adjuvants, additives, or residuals? Pediatrics 2003;112:1394-1397. URL: <www.pediatrics.org/cgi/content/full/112/6/1394>.

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