420 PART IV The Immune System in Health and Disease Whole-Organism Vaccines TABLE 18.4 Classification of common vaccines for humans As Table 18-4 indicates, many of the common vaccines cur- rently in use consist of inactivated (killed) or live but attenu Disease or pathogen Type of vaccine ated(avirulent) bacterial cells or viral particles. The primary THOLE ORGANISMS characteristics of these two types of vaccines are compared in Table 18-5 to one another and to dna vaccines that are cur- Bacterial cells rently being tested for use in humans Anthrax Attenuated Viruses and Bacteria cause Pertussis. Inactivate Immunity Without Disease Inactivated In some cases, microorganisms can be attenuated so that they lose their ability to cause significant disease(pathogenicity) but retain their capacity for transient growth within an inoc- Typhoid Live attenuated ulated host Attenuation often can be achieved by growing a viral particles pathogenic bacterium or virus for prolonged periods under abnormal culture conditions. This procedure selects mutants Hepatitis A nactivated that are better suited to growth in the abnormal culture con- Influenza Inactivated ditions and are therefore less capable of growth in the natural Measles host. For example, an attenuated strain of Mycobacterium bo vis called Bacillus Calmette-Guerin(BCG) was developed ve attenuated by growing M. bovis on a medium containing increasing con- Polio(Sabin) Live attenuated centrations of bile. After 13 years, this strain had adapted to growth in strong bile and had become sufficiently attenuated Inactivated that it was suitable as a vaccine for tuberculosis. The sabin polio vaccine and the measles vaccine both consist of attenu ve attenuate ated viral strains. The poliovirus used in the Sabin vaccine was attenuated by growth in monkey kidney epithelial cells Rubella nactivated The measles vaccine contains a strain of rubella virus that Varicella zoster(chickenpox) Live attenuated was grown in duck embryo cells and later in human cell lines Yellow fever Live attenuated Attenuated vaccines have advantages and disadvantages ecause of their capacity for transient growth, such vaccines provide prolonged immune-system exposure to the individ PURIFIED MACROMOLECULES ual epitopes on the attenuated organisms, resulting genicity and production of memory cells. As Toxoids a consequence, these vaccines often require only a single im- Inactivated exotoxin munization, eliminating the need for repeated boosters. This Inactivated exotoxin property is a major advantage in Third World countries, where epidemiologic studies have shown that roughly 20% of individuals fail to return for each subsequent booster. The Haemophilus influenzae pility of many attenuated vaccines to replicate within host type cells makes them particularly suitable for inducing a cell Neissera meningitidis mediated response Streptococcus pneumoniae 23 distinct capsular The Sabin polio vaccine, consisting of three attenuated polysaccharides strains of poliovirus, is administered orally to children on a Surface antigen sugar cube or in sugar liquid. The attenuated viruses colonize Hepatitis B the intestine and induce protective immunity to all three antigen(HBsAg strains of virulent poliovirus. Sabin vaccine in the intestines induces production of secretory IgA, which serves as an im -"There is an now also an acellular pertussis vaccine consisting of toxoids and portant defense against naturally acquired poliovirus. The inactivated bacteria components. vaccine also induces IgM and igg classes of antibody. Unlike 'Bacillus Calmette-Guerin(BCG)is an avirulent strain of Mycobacterium most other attenuated vaccines, which require a single im- bovis. munizing dose, the Sabin polio vaccine requires boostersWhole-Organism Vaccines As Table 18-4 indicates, many of the common vaccines cur￾rently in use consist of inactivated (killed) or live but attenu￾ated (avirulent) bacterial cells or viral particles. The primary characteristics of these two types of vaccines are compared in Table 18-5 to one another and to DNA vaccines that are cur￾rently being tested for use in humans. Attenuated Viruses and Bacteria Cause Immunity Without Disease In some cases, microorganisms can be attenuated so that they lose their ability to cause significant disease (pathogenicity) but retain their capacity for transient growth within an inoc￾ulated host. Attenuation often can be achieved by growing a pathogenic bacterium or virus for prolonged periods under abnormal culture conditions. This procedure selects mutants that are better suited to growth in the abnormal culture con￾ditions and are therefore less capable of growth in the natural host. For example, an attenuated strain of Mycobacterium bo￾vis called Bacillus Calmette-Guerin (BCG) was developed by growing M. bovis on a medium containing increasing con￾centrations of bile. After 13 years, this strain had adapted to growth in strong bile and had become sufficiently attenuated that it was suitable as a vaccine for tuberculosis. The Sabin polio vaccine and the measles vaccine both consist of attenu￾ated viral strains. The poliovirus used in the Sabin vaccine was attenuated by growth in monkey kidney epithelial cells. The measles vaccine contains a strain of rubella virus that was grown in duck embryo cells and later in human cell lines. Attenuated vaccines have advantages and disadvantages. Because of their capacity for transient growth, such vaccines provide prolonged immune-system exposure to the individ￾ual epitopes on the attenuated organisms, resulting in in￾creased immunogenicity and production of memory cells. As a consequence, these vaccines often require only a single im￾munization, eliminating the need for repeated boosters. This property is a major advantage in Third World countries, where epidemiologic studies have shown that roughly 20% of individuals fail to return for each subsequent booster. The ability of many attenuated vaccines to replicate within host cells makes them particularly suitable for inducing a cell￾mediated response. The Sabin polio vaccine, consisting of three attenuated strains of poliovirus, is administered orally to children on a sugar cube or in sugar liquid. The attenuated viruses colonize the intestine and induce protective immunity to all three strains of virulent poliovirus. Sabin vaccine in the intestines induces production of secretory IgA, which serves as an im￾portant defense against naturally acquired poliovirus. The vaccine also induces IgM and IgG classes of antibody. Unlike most other attenuated vaccines, which require a single im￾munizing dose, the Sabin polio vaccine requires boosters, 420 PART IV The Immune System in Health and Disease TABLE 18-4 Classification of common vaccines for humans Disease or pathogen Type of vaccine WHOLE ORGANISMS Bacterial cells Anthrax Inactivated Cholera Inactivated Pertussis* Inactivated Plague Inactivated Tuberculosis Live attenuated BCG† Typhoid Live attenuated Viral particles Hepatitis A Inactivated Influenza Inactivated Measles Live attenuated Mumps Live attenuated Polio (Sabin) Live attenuated Polio (Salk) Inactivated Rabies Inactivated Rotavirus Live attenuated Rubella Inactivated Varicella zoster (chickenpox) Live attenuated Yellow fever Live attenuated PURIFIED MACROMOLECULES Toxoids Diphtheria Inactivated exotoxin Tetanus Inactivated exotoxin Capsular polysaccharides Haemophilus influenzae Polysaccharide type b protein carrier Neissera meningitidis Polysaccharide Streptococcus pneumoniae 23 distinct capsular polysaccharides Surface antigen Hepatitis B Recombinant surface antigen (HBsAg) *There is an now also an acellular pertussis vaccine consisting of toxoids and inactivated bacteria components. † Bacillus Calmette-Guerin (BCG) is an avirulent strain of Mycobacterium bovis.