Appendix: Vaccines, Immune Globulins, & Other Complex Biologic Products

Vaccines and related biologic products constitute an important group of agents that bridge the disciplines of microbiology, infectious diseases, immunology, and immunopharmacology. A list of the most important preparations is provided here. The reader who requires more complete information is referred to the sources listed at the end of this appendix.

Active immunization consists of the administration of antigen to the host to induce formation of antibodies and cell-mediated immunity. Immunization is practiced to induce protection against many infectious agents and may utilize either inactivated (killed) materials or live attenuated agents (Table A–1). Desirable features of the ideal immunogen include complete prevention of disease, prevention of the carrier state, production of prolonged immunity with a minimum of immunizations, absence of toxicity, and suitability for mass immunization (eg, cheap and easy to administer). Active immunization is generally preferable to passive immunization—in most cases because higher antibody levels are sustained for longer periods of time, requiring less frequent immunization, and in some cases because of the development of concurrent cell-mediated immunity. However, active immunization requires time to develop and is therefore generally inactive at the time of a specific exposure (eg, for parenteral exposure to hepatitis B, concurrent hepatitis B IgG [passive antibodies] and active immunization are given to prevent illness).

Current recommendations for routine active immunization of children are given in Table A–2.

Passive immunization consists of transfer of immunity to a host using preformed immunologic products. From a practical standpoint, only immunoglobulins have been used for passive immunization, because passive administration of cellular components of the immune system has been technically difficult and associated with graft-versus-host reactions. Products of the cellular immune system (eg, interferons) have also been used in the therapy of a wide variety of hematologic and infectious diseases (see Chapter 55).

Passive immunization with antibodies may be accomplished with either animal or human immunoglobulins in varying degrees of purity. These may contain relatively high titers of antibodies directed against a specific antigen or, as is true for pooled immune globulin, may simply contain antibodies found in most of the population. Passive immunization is useful for (1) individuals unable to form antibodies (eg, congenital agammaglobulinemia); (2) prevention of disease when time does not permit active immunization (eg, postexposure); (3) for treatment of certain diseases normally prevented by immunization (eg, tetanus); and (4) for treatment of conditions for which active immunization is unavailable or impractical (eg, snakebite).

Complications from administration of human immunoglobulins are rare. The injections may be moderately painful, and rarely a sterile abscess may occur at the injection site. Transient hypotension and pruritus occasionally occur with the administration of intravenous immune globulin (IVIG) products, but generally are mild. Individuals with certain immunoglobulin deficiency states (IgA deficiency, etc) may occasionally develop hypersensitivity reactions to immune globulin that may limit therapy. Conventional immune globulin contains aggregates of IgG; it will cause severe reactions if given intravenously. However, if the passively administered antibodies are derived from animal sera, hypersensitivity reactions ranging from anaphylaxis to serum sickness may occur. Highly purified immunoglobulins, especially from rodents or lagomorphs, are the least likely to cause reactions. To avoid anaphylactic reactions, tests for hypersensitivity to the animal serum must be performed. If an alternative preparation is not available and administration of the specific antibody is deemed essential, desensitization can be carried out.

Antibodies derived from human serum not only avoid the risk of hypersensitivity reactions but also have a much longer half-life in humans (about 23 days for IgG antibodies) than those from animal sources (5–7 days or less). Consequently, much smaller doses of human antibody can be administered to provide therapeutic concentrations for several weeks. These advantages point to the desirability of using human antibodies for passive protection whenever possible. Materials available for passive immunization are summarized in Table A–3.

It is the physician’s responsibility to inform the patient of the risk of immunization and to use vaccines and antisera in an appropriate manner. This may require skin testing to assess the risk of an untoward reaction. Some of the risks previously described are, however, currently unavoidable; on balance, the patient and society are clearly better off accepting the risks for routinely administered immunogens (eg, influenza and tetanus vaccines).

Manufacturers should be held legally accountable for failure to adhere to existing standards for production of biologicals. However, in the present litigious atmosphere of the USA, the filing of large liability claims by the statistically inevitable victims of good public health practice has caused many manufacturers to abandon efforts to develop and produce low-profit but medically valuable therapeutic agents such as vaccines. Since the use and sale of these products are subject to careful review and approval by government bodies such as the Surgeon General’s Advisory Committee on Immunization Practices and the US Food and Drug Administration, “strict product liability” (liability without fault) may be an inappropriate legal standard to apply when rare reactions to biologicals, produced and administered according to government guidelines, are involved.

Every adult, whether traveling or not, should be immunized with tetanus toxoid and should also be fully immunized against poliomyelitis, measles (for those born after 1956), and diphtheria. In addition, every traveler must fulfill the immunization requirements of the health authorities of the countries to be visited. These are listed in Health Information for International Travel, available from the Superintendent of Documents, US Government Printing Office, Washington, DC 20402. A useful website is http://wwwnc.cdc.gov/travel/. The Medical Letter on Drugs and Therapeutics also offers periodically updated recommendations for international travelers (see Treatment Guidelines from The Medical Letter, 2012;10:45). Immunizations received in preparation for travel should be recorded on the International Certificate of Immunization. Note: Smallpox vaccination is not recommended or required for travel in any country.