Chapter 116. Immunization Principles and Vaccine Use (Part 1)

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Harrison's Internal Medicine Chapter 116. Immunization Principles and Vaccine Use Principles of Immunization The immune system, composed of a variety of cell types and soluble factors, is geared toward the recognition of and response to "foreign" substances termed antigens. Vaccines convey antigens from living or killed microorganisms (or protein or carbohydrate molecules derived from these antigens) to elicit immune responses that are generally protective but can occasionally backfire and cause harm to the recipient. Specific immune responses, which interrupt the infectious process, generally take the form of immunoglobulin proteins called antibodies and/or activated immune cells that recognize particular antigens from an...

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Chapter 116. Immunization Principles and Vaccine Use (Part 1) Harrison's Internal Medicine > Chapter 116. Immunization Principles and Vaccine Use Principles of Immunization The immune system, composed of a variety of cell types and soluble factors, is geared toward the recognition of and response to "foreign" substances termed antigens. Vaccines convey antigens from living or killed microorganisms (or protein or carbohydrate molecules derived from these antigens) to elicit immune responses that are generally protective but can occasionally backfire and cause harm to the recipient. Specific immune responses, which interrupt the infectious process, generally take the form of immunoglobulin proteins called antibodies and/or activated immune cells that recognize particular antigens from
an infectious agent. Immunity is medically induced by active or passive immunization. Active immunization—i.e., the administration of a vaccine— induces immunity that is usually long-lasting and is sometimes life-long. In contrast, passive immunization—i.e., the administration of exogenously produced immune substances or of protective products made in animals—elicits temporary immunity that dissipates with the turnover of the administered protective substances. Used together, the two methods can produce a complementary effect; this is the case, for example, with the coadministration of hepatitis B vaccine and hepatitis B immune globulin. Caution is required, however: the combination of active and passive immunization can also interfere with the development of immunity—e.g., when measles vaccine is administered within 6 weeks of measles immunoglobulin. When multiple species or serotypes of an organism exist and share common, cross-reactive antigens, vaccination may induce broad immunity to all or most of the related forms or may result in serotype-specific immunity against the immunizing strain alone. One of the virtues of whole-organism vaccines is their potential to contain all the protective antigens of the organism. This advantage is balanced by the possibility of adverse responses to reactive but nonprotective antigens present in the mix. Because the immune response is genetically controlled, all individuals cannot be expected to respond identically to the same vaccine. Additional vaccine constituents affect immunogenicity, efficacy, and
safety and may render one formulation superior to another formulation of the same antigens (see "Adjuvants," below). Approaches to Active Immunization The two standard approaches to active immunization are (1) the use of live, generally attenuated infectious agents (e.g., measles virus); and (2) the use of inactivated agents (e.g., influenza virus), their constituents (e.g., Bordetella pertussis), or their products, which are now commonly obtainable through genetic engineering (e.g., hepatitis B vaccine). For many diseases (e.g., poliomyelitis), both live and inactivated vaccines have been employed, each offering advantages and disadvantages. Live attenuated vaccines consisting of selected or genetically altered organisms that are avirulent or dramatically attenuated, yet remain immunogenic, typically generate long-lasting immunity. These vaccines are designed to cause a subclinical or mild illness and an immune response that mimics natural infection. They offer the advantage of microbial replication in vivo, which simulates natural infection; they may confer life-long protection with one dose; they can present all potential antigens, including those made only in vivo, thus overcoming immunogenetic restrictions in some hosts; and they can reach the local sites most relevant to the induction of protective immunity.
Nonliving vaccines typically require multiple doses and periodic boosters for the maintenance of immunity. The exceptions to this rule are the pure polysaccharide vaccines, whose effects cannot be boosted by additional exposures because polysaccharides do not elicit immunologic memory. Nonliving vaccines administered parenterally fail to induce mucosal immunity because they lack a delivery system that can effectively transport them to local mucosal antigen- processing cells. Nonetheless, nonliving parenteral vaccines can be extremely efficacious. For example, hepatitis A vaccine appears to be effective in nearly 100% of recipients. Currently available nonliving vaccines consist of inactivated whole organisms (e.g., plague vaccine), detoxified protein exotoxins (e.g., tetanus toxoid), recombinant protein antigens (e.g., hepatitis B vaccine), or carbohydrate antigens—either soluble purified capsular material (e.g., serotype-specific Streptococcus pneumoniae polysaccharides) or polysaccharide conjugated to a protein carrier to induce a memory response (e.g., Hib polysaccharide conjugated to a suitable protein moiety). Despite their many advantages, live vaccines are not always preferable. For example, after several decades of extensive use, live oral polio vaccine (OPV) is no longer recommended in the United States because of the rare but real risk of vaccine-associated polio due to reversion to virulence. However, the WHO continues to recommend OPV for use in the developing world because of lower costs and logistical advantages.