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

Harrisons Internal Medicine Chapter 116. Immunization Principles and Vaccine UsePrinciples of ImmunizationThe 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 froman...
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Chapter 116. Immunization Principles and Vaccine Use (Part 1) Chapter 116. Immunization Principles and Vaccine Use (Part 1) Harrisons Internal Medicine > Chapter 116. Immunization Principlesand Vaccine Use Principles of Immunization The immune system, composed of a variety of cell types and solublefactors, is geared toward the recognition of and response to foreign substancestermed antigens. Vaccines convey antigens from living or killed microorganisms(or protein or carbohydrate molecules derived from these antigens) to elicitimmune responses that are generally protective but can occasionally backfire andcause harm to the recipient. Specific immune responses, which interrupt theinfectious process, generally take the form of immunoglobulin proteins calledantibodies and/or activated immune cells that recognize particular antigens froman infectious agent. Immunity is medically induced by active or passiveimmunization. Active immunization—i.e., the administration of a vaccine—induces immunity that is usually long-lasting and is sometimes life-long. Incontrast, passive immunization—i.e., the administration of exogenously producedimmune substances or of protective products made in animals—elicits temporaryimmunity that dissipates with the turnover of the administered protectivesubstances. Used together, the two methods can produce a complementary effect;this is the case, for example, with the coadministration of hepatitis B vaccine andhepatitis B immune globulin. Caution is required, however: the combination ofactive and passive immunization can also interfere with the development ofimmunity—e.g., when measles vaccine is administered within 6 weeks of measlesimmunoglobulin. When multiple species or serotypes of an organism exist and sharecommon, cross-reactive antigens, vaccination may induce broad immunity to all ormost of the related forms or may result in serotype-specific immunity against theimmunizing strain alone. One of the virtues of whole-organism vaccines is theirpotential to contain all the protective antigens of the organism. This advantage isbalanced by the possibility of adverse responses to reactive but nonprotectiveantigens present in the mix. Because the immune response is geneticallycontrolled, all individuals cannot be expected to respond identically to the samevaccine. Additional vaccine constituents affect immunogenicity, efficacy, andsafety and may render one formulation superior to another formulation of the sameantigens (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 ofinactivated agents (e.g., influenza virus), their constituents (e.g., Bordetellapertussis), or their products, which are now commonly obtainable through geneticengineering (e.g., hepatitis B vaccine). For many diseases (e.g., poliomyelitis),both live and inactivated vaccines have been employed, each offering advantagesand disadvantages. Live attenuated vaccines consisting of selected or genetically alteredorganisms that are avirulent or dramatically attenuated, yet remain immunogenic,typically generate long-lasting immunity. These vaccines are designed to cause asubclinical or mild illness and an immune response that mimics natural infection.They offer the advantage of microbial replication in vivo, which simulates naturalinfection; they may confer life-long protection with one dose; they can present allpotential antigens, including those made only in vivo, thus overcomingimmunogenetic restrictions in some hosts; and they can reach the local sites mostrelevant to the induction of protective immunity. Nonliving vaccines typically require multiple doses and periodic boostersfor the maintenance of immunity. The exceptions to this rule are the purepolysaccharide vaccines, whose effects cannot be boosted by additional exposuresbecause polysaccharides do not elicit immunologic memory. Nonliving vaccinesadministered parenterally fail to induce mucosal immunity because they lack adelivery system that can effectively transport them to local mucosal antigen-processing cells. Nonetheless, nonliving parenteral vaccines can be extremelyefficacious. For example, hepatitis A vaccine appears to be effective in nearly100% of recipients. Currently available nonliving vaccines consist of inactivatedwhole organisms (e.g., plague vaccine), detoxified protein exotoxins (e.g., tetanustoxoid), recombinant protein antigens (e.g., hepatitis B vaccine), or carbohydrateantigens—either soluble purified capsular material (e.g., serotype-specificStreptococcus pneumoniae polysaccharides) or polysaccharide conjugat ...